Small cell lung cancer

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Last updated on 2024-12-02:51 regimens on this page
105 variants on this page
=Guidelines=
Given the rapid change in evidence in many areas of hematology/oncology, readers are encouraged to consider any guideline published 5+ years ago to be for historical purposes, only.
==ASCO==
*2024: Kalemkerian et al. Systemic Therapy for Small Cell Lung Cancer: ASCO Guideline Rapid Recommendation Update EuroPMC
**2023: Khurshid et al. Systemic Therapy for Small-Cell Lung Cancer: ASCO-Ontario Health (Cancer Care Ontario) Guideline EuroPMC
*2021: Daly et al. Radiation Therapy for Small-Cell Lung Cancer: ASCO Guideline Endorsement of an ASTRO Guideline EuroPMC
*2020: Schneider et al. Lung Cancer Surveillance After Definitive Curative-Intent Therapy: ASCO Guideline EuroPMC
*2015: Rudin et al. Treatment of small-cell lung cancer: American Society of Clinical Oncology endorsement of the American College of Chest Physicians guideline EuroPMC
==ESMO==
*2021: Dingemans et al. Small-cell lung cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up EuroPMC
**2013: Früh et al. Small-cell lung cancer (SCLC): ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. EuroPMC
**2010: Sørensen et al. Small-cell lung cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up EuroPMC
**2009: Sørensen & Felip. Small-cell lung cancer: ESMO clinical recommendations for diagnosis, treatment and follow-up EuroPMC
**2005: Felip et al. ESMO Minimum Clinical Recommendations for diagnosis, treatment and follow-up of small-cell lung cancer (SCLC) EuroPMC
**2001: ESMO Minimum Clinical Recommendations for diagnosis, treatment and follow-up of small-cell lung cancer (SCLC) EuroPMC
==NCCN==
*NCCN Guidelines - Small Cell Lung Cancer
**2021: Ganti et al. Small Cell Lung Cancer, Version 2.2022, NCCN Clinical Practice Guidelines in Oncology EuroPMC
**2013: Kalemkerian et al. Small cell lung cancer. EuroPMC
**2011: Kalemkerian et al. Small cell lung cancer. EuroPMC
**2006: Johnson et al. Small cell lung cancer clinical practice guidelines in oncology. EuroPMC
**2004: Authors not listed. Small cell lung cancer. Clinical practice guidelines in oncology. EuroPMC
==SEOM-GECP==
*2023: García-Campelo et al. SEOM-GECP clinical guidelines for diagnosis, treatment, and follow-up of small-cell lung cancer (SCLC) (2022) EuroPMC
==SITC==
*2022: Govindan et al. Society for Immunotherapy of Cancer (SITC) clinical practice guideline on immunotherapy for the treatment of lung cancer and mesothelioma EuroPMC
=Limited stage, induction=
==Carboplatin & Etoposide (CE)==
EP: Etoposide, Paraplatin (Carboplatin)
===Regimen variant #1, 2 days of oral etoposide per cycle===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Lee et al. 2009 (LLCG-STUDY-12)	2003-2006 	Phase 3 (C)	CE & Thalidomide, then RT	Did not meet primary endpoint of OSMedian OS: 10.5 vs 10.1 mo(HR 0.92, 95% CI 0.79-1.08)
====Chemotherapy====
*Carboplatin (Paraplatin) AUC 6 IV once on day 1
*Etoposide (Vepesid) 120 mg/m2 IV once on day 1, then 100 mg PO twice per day on days 2 & 3
21-day cycle for up to 6 cycles
====Subsequent treatment====
*LLCG-STUDY-12, patients with PR/CR: Definitive thoracic radiotherapy and prophylactic cranial irradiation, approximately 3 weeks after the last cycle, "according to local practice".
===Regimen variant #2, 1 day of oral etoposide per cycle===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Lee et al. 2009 (LLCG-STUDY-12)	2003-2006 	Phase 3 (C)	CE & Thalidomide, then RT	Did not meet primary endpoint of OSMedian OS: 10.5 vs 10.1 mo(HR 0.92, 95% CI 0.79-1.08)
====Chemotherapy====
*Carboplatin (Paraplatin) AUC 6 IV once on day 1
*Etoposide (Vepesid) 120 mg/m2 IV once per day on days 1 & 2, then 100 mg PO twice per day on day 3
21-day cycle for up to 6 cycles
====Subsequent treatment====
*LLCG-STUDY-12, patients with PR/CR: Definitive thoracic radiotherapy and prophylactic cranial irradiation, approximately 3 weeks after the last cycle, "according to local practice".
===References===
# LLCG-STUDY-12: Lee SM, Woll PJ, Rudd R, Ferry D, O'Brien M, Middleton G, Spiro S, James L, Ali K, Jitlal M, Hackshaw A. Anti-angiogenic therapy using thalidomide combined with chemotherapy in small cell lung cancer: a randomized, double-blind, placebo-controlled trial. J Natl Cancer Inst. 2009 Aug 5;101(15):1049-57. Epub 2009 Jul 16. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT00061919
==Cisplatin & Etoposide (EP)==
EP: Etoposide, Platinol (Cisplatin)
===Regimen===
Study 	Dates of enrollment	Evidence
Evans et al. 1985	1981-1984 	Phase 2
Note: Patients with limited stage disease responding to therapy received prophylactic cranial irradiation, 400 cGy fractions once per day x 5 fractions (total dose: 2000 cGy) over 5 days between cycles 3 and 4.
====Chemotherapy====
*Cisplatin (Platinol) 25 mg/m2 IV slow push once per day on days 1 to 3, given second
*Etoposide (Vepesid) 100 mg/m2 IV over at least 30 minutes once per day on days 1 to 3, given first
====Supportive therapy====
*Dexamethasone (Decadron) 10 mg IV once per day on days 1 to 3, prior to chemotherapy
*Metoclopramide (Reglan) 10 mg IV or PO once per day on days 1 to 3, prior to chemotherapy
*Prochlorperazine (Compazine) 10 mg IM or PO once per day on days 1 to 3, prior to chemotherapy
*"No special efforts were made to hydrate the patients," though PO fluid intake was encouraged, and 500 mL normal saline was given with etoposide infusion.
21- to 28-day cycle for 6 cycles
====Subsequent treatment====
*Definitive thoracic radiation
===References===
# Evans WK, Shepherd FA, Feld R, Osoba D, Dang P, Deboer G. VP-16 and cisplatin as first-line therapy for small-cell lung cancer. J Clin Oncol. 1985 Nov;3(11):1471-7. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
=Limited stage, definitive chemoradiotherapy=
==Carboplatin, Etoposide, RT==
EP & RT: Etoposide, Paraplatin (Carboplatin), Radiation Therapy
===Regimen variant #1===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Skarlos et al. 2001	1993-1999 	Randomized Phase 2 (E-switch-ic)	Carboplatin, Etoposide, RT; early HTRT	Might have higher ORR (primary endpoint)
====Chemotherapy====
*Carboplatin (Paraplatin) AUC 6 IV over 60 minutes once on day 1, given first, before etoposide
*Etoposide (Vepesid) 100 mg/m2 IV over 2 hours once per day on days 1 to 3, given second, after carboplatin
====Radiotherapy====
*Concurrent hyperfractionated thoracic radiation therapy (HTRT), 150 cGy fractions given twice per day (at least 4, but preferably 6 hours between fractions) x 30 fractions (total dose: 4500 cGy) over 3 weeks. Skarlos et al. 2001 examined two different timings for radiation therapy. There was no significant difference between early vs. late HTRT, though there was a trend toward higher response rate for late HTRT. Early HTRT was given during cycle 1 of chemotherapy; late HTRT was given during cycle 4 of chemotherapy.
21-day cycle for up to 6 cycles
====Subsequent treatment====
*Skarlos et al. 2001, patients with CR: Prophylactic cranial irradiation
===Regimen variant #2===
Study 	Dates of enrollment	Evidence
Okamoto et al. 1999	1995-1996 	Phase 2
====Eligibility criteria====
*At least 70 years old
====Chemotherapy====
*Carboplatin (Paraplatin) AUC 5 IV over 60 minutes once on day 1, given first
*Etoposide (Vepesid) 100 mg/m2 IV over 60 minutes once per day on days 1 to 3, given second
====Radiotherapy====
*Thoracic radiation, given third
*Palliative radiation therapy was allowed to control persistent pain from bony metastases
====Supportive therapy====
*Dexamethasone (Decadron) 8 mg IV once per day on days 1 to 3, prior to chemotherapy
*Granisetron 40 mcg/kg IV once per day on days 1 to 3, prior to chemotherapy
*G-CSF (type not specified) 2 mcg/kg SC given for grade 3 or greater leukopenia/neutropenia
28-day cycle for up to 4 cycles
===References===
# Okamoto H, Watanabe K, Nishiwaki Y, Mori K, Kurita Y, Hayashi I, Masutani M, Nakata K, Tsuchiya S, Isobe H, Saijo N. Phase II study of area under the plasma-concentration-versus-time curve-based carboplatin plus standard-dose intravenous etoposide in elderly patients with small-cell lung cancer. J Clin Oncol. 1999 Nov;17(11):3540-5. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
# Skarlos DV, Samantas E, Briassoulis E, Panoussaki E, Pavlidis N, Kalofonos HP, Kardamakis D, Tsiakopoulos E, Kosmidis P, Tsavdaridis D, Tzitzikas J, Tsekeris P, Kouvatseas G, Zamboglou N, Fountzilas G; Hellenic Cooperative Oncology Group. Randomized comparison of early versus late hyperfractionated thoracic irradiation concurrently with chemotherapy in limited disease small-cell lung cancer: a randomized phase II study of the Hellenic Cooperative Oncology Group (HeCOG). Ann Oncol. 2001 Sep;12(9):1231-8. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
==Cisplatin & Etoposide (EP) & RT==
EP & RT: Etoposide, Platinol (Cisplatin), Radiation Therapy
PE + RT: Platinol (Cisplatin), Etoposide, Radiation Therapy
===Regimen variant #1, 60/360/45===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Turrisi et al. 1999 (Intergroup 0096)	1989-1992 	Phase 3 (E-esc)	EP & RT; once per day RT	Seems to have longer OS
====Chemotherapy====
*Cisplatin (Platinol) 60 mg/m2 IV once on day 1 
*Etoposide (Vepesid) 120 mg/m2 IV once per day on days 1 to 3
====Radiotherapy====
*Concurrent radiation therapy, 150 cGy fractions given twice per day x 30 fractions over 3 weeks, given during cycle 1 of chemotherapy (total dose: 4500 cGy)
21-day cycle for 4 cycles
====Subsequent treatment====
*After completing 4 cycles of chemotherapy, patients were restaged. Because of the high rate of brain metastases (50%), patients with CR were offered prophylactice cranial irradiation
===Regimen variant #2, 70/300/52.5, early RT===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy	Comparative Toxicity
Sun et al. 2013 (SMC 2003-02-016)	2003-2010 	Phase 3 (C)	EP & RT; late RT	Non-inferior CR rate	Seems to have higher rates of neutropenic fever
====Chemotherapy====
*Cisplatin (Platinol) 70 mg/m2 IV once on day 1 
*Etoposide (Vepesid) 100 mg/m2 IV once per day on days 1 to 3
====Radiotherapy====
*Concurrent radiation therapy, 210 cGy fractions x 25 fractions over 5 weeks, given during cycle 1 of chemotherapy (total dose: 5250 cGy)
21-day cycle for 4 cycles
===Regimen variant #3, 70/300/52.5, late RT===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy 	Comparative Toxicity
Sun et al. 2013 (SMC 2003-02-016)	2003-2010 	Phase 3 (E-switch-ic)	EP & RT; early RT	Non-inferior CR rate (primary endpoint)	Seems to have lower rates of neutropenic fever
====Chemotherapy====
*Cisplatin (Platinol) 70 mg/m2 IV once on day 1 
*Etoposide (Vepesid) 100 mg/m2 IV once per day on days 1 to 3
====Radiotherapy====
*Concurrent radiation therapy, 210 cGy fractions x 25 fractions over 5 weeks, given during cycle 3 of chemotherapy (total dose: 5250 cGy)
21-day cycle for 4 cycles
===Regimen variant #4, 75/180/45, pre-planned dose reduction===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy 	Comparative Toxicity
Bunn et al. 1995	1989-1991 	Phase 3 (C)	EP & RT; with GM-CSF support	Did not meet secondary endpoints	Less toxic
Note: toxicity was the primary endpoint in this study.
====Chemotherapy====
*Cisplatin (Platinol) as follows:
**Cycles 1 to 3: 25 mg/m2 IV once per day on days 1 to 3
**Cycles 4 to 6: 40 mg/m2 IV once on day 1
*Etoposide (Vepesid) as follows:
**Cycles 1 to 3: 60 mg/m2 IV once per day on days 1 to 3
**Cycles 4 to 6: 50 mg/m2 IV once per day on days 1 to 3
====Radiotherapy====
*Concurrent radiation therapy during cycles 1 & 2, 180 cGy fractions x 25 fractions (total dose: 4500 cGy)
21-day cycle for 6 cycles
===Regimen variant #5, 75/300/45===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Faivre-Finn et al. 2017 (CONVERT)	2008-2013 	Phase 3 (C)	EP & RT; once per day RT	Did not meet primary endpoint of OS1Median OS: 30 vs 25.4 mo(HR 0.88, 95% CI 0.72-1.09)
1Reported efficacy is based on the 2024 update.
====Chemotherapy====
*Cisplatin (Platinol) 75 mg/m2 IV once on day 1
*Etoposide (Vepesid) 100 mg/m2 IV once per day on days 1 to 3
====Radiotherapy====
*Concurrent radiation therapy, 150 cGy fractions given twice per day x 30 fractions over 3 weeks, given during cycle 2 of chemotherapy (total dose: 4500 cGy)
21-day cycle for 4 or 6 cycles
===Regimen variant #6, 75/300/45, split doses of cisplatin===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Faivre-Finn et al. 2017 (CONVERT)	2008-2013 	Phase 3 (C)	EP & RT; once per day RT	Did not meet primary endpoint of OS1Median OS: 30 vs 25.4 mo(HR 0.88, 95% CI 0.72-1.09)
1Reported efficacy is based on the 2024 update.
====Chemotherapy====
*Cisplatin (Platinol) 25 mg/m2 IV once per day on days 1 to 3
*Etoposide (Vepesid) 100 mg/m2 IV once per day on days 1 to 3
====Radiotherapy====
*Concurrent radiation therapy, 150 cGy fractions given twice per day x 30 fractions over 3 weeks, given during cycle 2 of chemotherapy (total dose: 4500 cGy)
21-day cycle for 4 or 6 cycles
===Regimen variant #7, 75/700/42, partially oral etoposide===
Study 	Dates of enrollment	Evidence 	Comparator	Comparative Efficacy
Sundstrøm et al. 2002	1989-1994 	Phase 3 (E-switch-ic)	CEV & RT 	Longer OS
Note: Oral etoposide to be taken on an empty stomach.
====Chemotherapy====
*Cisplatin (Platinol) 75 mg/m2 IV once on day 1 
*Etoposide (Vepesid) 100 mg/m2 IV once on day 1, then 200 mg/m2 PO once per day on days 2 to 4
====Radiotherapy====
*Concurrent thoracic radiation therapy, 280 cGy fractions once per day x 15 fractions (total dose: 4200 cGy) over 3 weeks, given "between the third and fourth chemotherapy courses"
====Supportive therapy====
*"Standard prehydration and posthydration procedures were followed in conjunction with cisplatin administration."
21-day cycle for up to 5 cycles
====Subsequent treatment====
*Sundstrøm et al. 2002, patients with CR: Prophylactic cranial irradiation
===Regimen variant #8, 80/240/50===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
McClay et al. 2005 (CALGB 9235)	1993-1999 	Phase 3 (E-de-esc)	EP, Tamoxifen, RT	Did not meet primary endpoint of OS
====Chemotherapy====
*Cisplatin (Platinol) 80 mg/m2 IV once on day 1 
*Etoposide (Vepesid) 80 mg/m2 IV once per day on days 1 to 3
====Radiotherapy====
*Concurrent thoracic radiation therapy, 200 cGy fractions once per day x 25 fractions (total dose: 5000 cGy) over 5 weeks, started on cycle 4 day 1 of chemotherapy
21-day cycle for 5 cycles
===Regimen variant #9, 80/300/45, 1 cycle of chemo===
Study 	Dates of enrollment	Evidence
Saito et al. 2006 (WJTOG 9902)	2000-2002 	Phase 2
Kubota et al. 2013 (JCOG0202) 	2002-2006 	Non-randomized part of phase 3 RCT
====Chemotherapy====
*Cisplatin (Platinol) 80 mg/m2 IV once on day 1 
*Etoposide (Vepesid) 100 mg/m2 IV once per day on days 1 to 3
====Radiotherapy====
*Concurrent thoracic radiation therapy, 150 cGy fractions given twice per day (at least 4, but preferably 6 hours between fractions) x 30 fractions (total dose: 4500 cGy) over 3 weeks, started on cycle 1 day 2 of chemotherapy
28-day course
====Subsequent treatment====
*WJTOG 9902: IP consolidation
*JCOG0202: EP x 3 versus IP consolidation
===Regimen variant #10, 80/300/45, 4 cycles of chemo===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Takada et al. 2002 (JCOG 9104)	1991-1995 	Phase 3 (E-switch-ic)	EP, then RT	Might have longer OS
====Chemotherapy====
*Cisplatin (Platinol) 80 mg/m2 IV once on day 1 
*Etoposide (Vepesid) 100 mg/m2 IV once per day on days 1 to 3
====Radiotherapy====
*Concurrent thoracic radiation therapy, 150 cGy fractions given twice per day (4 or more hours between fractions) x 30 fractions (total dose: 4500 cGy) over 3 weeks, started on cycle 1 day 2 of chemotherapy
28-day cycle for 4 cycles
====Subsequent treatment====
*JCOG 9104, patients with CR or near-CR ("a scar-like shadow on chest films but no positive cytology and/or bronchoscopic biopsy"): Prophylactic cranial irradiation
===Regimen variant #11, 90/300/39.9===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Sculier et al. 2008	1993-2006 	Phase 3 (E-switch-ic)	EP & RT; daily cisplatin	Did not meet primary endpoint of OS
====Chemotherapy====
*Cisplatin (Platinol) 90 mg/m2 IV once on day 1
*Etoposide (Vepesid) 100 mg/m2 IV once per day on days 1 to 3
====Radiotherapy====
*Concurrent radiation therapy, 266 cGy fractions once per day x 15 fractions over 3 weeks, given during cycle 1 of chemotherapy (total dose: 3990 cGy)
21-day cycle for up to 6 cycles
===References===
# Bunn PA Jr, Crowley J, Kelly K, Hazuka MB, Beasley K, Upchurch C, Livingston R; SWOG. Chemoradiotherapy with or without granulocyte-macrophage colony-stimulating factor in the treatment of limited-stage small-cell lung cancer: a prospective phase III randomized study of the Southwest Oncology Group. J Clin Oncol. 1995 Jul;13(7):1632-41. Erratum in: J Clin Oncol 1995 Nov;13(11):2860. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
# Intergroup 0096: Turrisi AT 3rd, Kim K, Blum R, Sause WT, Livingston RB, Komaki R, Wagner H, Aisner S, Johnson DH. Twice-daily compared with once-daily thoracic radiotherapy in limited small-cell lung cancer treated concurrently with cisplatin and etoposide. N Engl J Med. 1999 Jan 28;340(4):265-71. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
# JCOG 9104: Takada M, Fukuoka M, Kawahara M, Sugiura T, Yokoyama A, Yokota S, Nishiwaki Y, Watanabe K, Noda K, Tamura T, Fukuda H, Saijo N. Phase III study of concurrent versus sequential thoracic radiotherapy in combination with cisplatin and etoposide for limited-stage small-cell lung cancer: results of the Japan Clinical Oncology Group Study 9104. J Clin Oncol. 2002 Jul 15;20(14):3054-60. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC content property of HemOnc.org
# Sundstrøm S, Bremnes RM, Kaasa S, Aasebø U, Hatlevoll R, Dahle R, Boye N, Wang M, Vigander T, Vilsvik J, Skovlund E, Hannisdal E, Aamdal S; Norwegian Lung Cancer Study Group. Cisplatin and etoposide regimen is superior to cyclophosphamide, epirubicin, and vincristine regimen in small-cell lung cancer: results from a randomized phase III trial with 5 years' follow-up. J Clin Oncol. 2002 Dec 15;20(24):4665-72. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
#Schild SE, Bonner JA, Shanahan TG, Brooks BJ, Marks RS, Geyer SM, Hillman SL, Farr GH Jr, Tazelaar HD, Krook JE, Geoffroy FJ, Salim M, Arusell RM, Mailliard JA, Schaefer PL, Jett JR. Long-term results of a phase III trial comparing once-daily radiotherapy with twice-daily radiotherapy in limited-stage small-cell lung cancer. Int J Radiat Oncol Biol Phys. 2004 Jul 15;59(4):943-51. link to original article EuroPMC
# CALGB 9235: McClay EF, Bogart J, Herndon JE 2nd, Watson D, Evans L, Seagren SL, Green MR; CALGB. A phase III trial evaluating the combination of cisplatin, etoposide, and radiation therapy with or without tamoxifen in patients with limited-stage small cell lung cancer: Cancer and Leukemia Group B Study (9235). Am J Clin Oncol. 2005 Feb;28(1):81-90. link to original article dosing details in abstract have been reviewed by our editors EuroPMC
# WJTOG 9902: Saito H, Takada Y, Ichinose Y, Eguchi K, Kudoh S, Matsui K, Nakagawa K, Takada M, Negoro S, Tamura K, Ando M, Tada T, Fukuoka M; West Japan Thoracic Oncology Group. Phase II study of etoposide and cisplatin with concurrent twice-daily thoracic radiotherapy followed by irinotecan and cisplatin in patients with limited-disease small-cell lung cancer: West Japan Thoracic Oncology Group 9902. J Clin Oncol. 2006 Nov 20;24(33):5247-52. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
# Sculier JP, Lafitte JJ, Efremidis A, Florin MC, Lecomte J, Berchier MC, Richez M, Berghmans T, Scherpereel A, Meert AP, Koumakis G, Leclercq N, Paesmans M, Van Houtte P; European Lung Cancer Working Party. A phase III randomised study of concomitant induction radiochemotherapy testing two modalities of radiosensitisation by cisplatin (standard versus daily) for limited small-cell lung cancer. Ann Oncol. 2008 Oct;19(10):1691-7. Epub 2008 May 25. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
# SMC 2003-02-016: Sun JM, Ahn YC, Choi EK, Ahn MJ, Ahn JS, Lee SH, Lee DH, Pyo H, Song SY, Jung SH, Jo JS, Jo J, Sohn HJ, Suh C, Lee JS, Kim SW, Park K. Phase III trial of concurrent thoracic radiotherapy with either first- or third-cycle chemotherapy for limited-disease small-cell lung cancer. Ann Oncol. 2013 Aug;24(8):2088-92. Epub 2013 Apr 16. Erratum in: Ann Oncol. 2014 Aug;25(8):1672. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT01125995
# JCOG0202: Kubota K, Hida T, Ishikura S, Mizusawa J, Nishio M, Kawahara M, Yokoyama A, Imamura F, Takeda K, Negoro S, Harada M, Okamoto H, Yamamoto N, Shinkai T, Sakai H, Matsui K, Nakagawa K, Shibata T, Saijo N, Tamura T; JCOG. Etoposide and cisplatin versus irinotecan and cisplatin in patients with limited-stage small-cell lung cancer treated with etoposide and cisplatin plus concurrent accelerated hyperfractionated thoracic radiotherapy (JCOG0202): a randomised phase 3 study. Lancet Oncol. 2014 Jan;15(1):106-13. Epub 2013 Dec 3. link to original article dosing details in abstract have been reviewed by our editors EuroPMC NCT00144989
# CONVERT: Faivre-Finn C, Snee M, Ashcroft L, Appel W, Barlesi F, Bhatnagar A, Bezjak A, Cardenal F, Fournel P, Harden S, Le Pechoux C, McMenemin R, Mohammed N, O'Brien M, Pantarotto J, Surmont V, Van Meerbeeck JP, Woll PJ, Lorigan P, Blackhall F; CONVERT Study Team. Concurrent once-daily versus twice-daily chemoradiotherapy in patients with limited-stage small-cell lung cancer (CONVERT): an open-label, phase 3, randomised, superiority trial. Lancet Oncol. 2017 Aug;18(8):1116-1125. Epub 2017 Jun 20. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors EuroPMC NCT00433563
##Update: Walls GM, Mistry H, Barlesi F, Bezjak A, Pechoux CL, O'Brien M, Van Meerbeeck JP, Blackhall F, Faivre-Finn C. Long-Term Outcomes After Concurrent Once- or Twice-Daily Chemoradiation in Limited-Stage Small Cell Lung Cancer: A Brief Report From the CONVERT Trial. Int J Radiat Oncol Biol Phys. 2024 Aug 1;119(5):1386-1390. Epub 2024 Mar 21. link to original article EuroPMC
#CALGB 30610: NCT00632853
=Limited stage, adjuvant therapy=
==Cisplatin & Etoposide (EP)==
EP: Etoposide & Platinol (Cisplatin)
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Kenmotsu et al. 2020 (JCOG1205/1206)	2013-2018 	Phase 3 (C)	Cisplatin & Irinotecan	Did not meet primary endpoint of RFSRFS36: 65.4% vs 69%(HR 0.93, 95% CI 0.58-1.50)
====Preceding treatment====
*Complete surgical resection
====Chemotherapy====
*Cisplatin (Platinol) 80 mg/m2 IV once on day 1
*Etoposide (Vepesid) 100 mg/m2 IV once per day on days 1 to 3
21-day cycle for up to 4 cycles
===References===
#JCOG1205/1206: Kenmotsu H, Niho S, Tsuboi M, Wakabayashi M, Ishii G, Nakagawa K, Daga H, Tanaka H, Saito H, Aokage K, Takahashi T, Menju T, Kasai T, Yoshino I, Minato K, Okada M, Eba J, Asamura H, Ohe Y, Watanabe SI. Randomized Phase III Study of Irinotecan Plus Cisplatin Versus Etoposide Plus Cisplatin for Completely Resected High-Grade Neuroendocrine Carcinoma of the Lung: JCOG1205/1206. J Clin Oncol. 2020 Dec 20;38(36):4292-4301. Epub 2020 Nov 2. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC UMIN000010298
=Limited stage, consolidation after upfront therapy=
==Cisplatin & Irinotecan (IC)==
IP: Irinotecan, Platinol (Cisplatin)
===Regimen===
Study 	Dates of enrollment	Evidence
Saito et al. 2006 (WJTOG 9902)	2000-2002 	Phase 2
====Preceding treatment====
*Definitive EP & RT
====Chemotherapy====
*Cisplatin (Platinol) 60 mg/m2 IV once on day 1
*Irinotecan (Camptosar) 60 mg/m2 IV once per day on days 1, 8, 15
====Supportive therapy====
*G-CSF (no additional details given) starting after day 4
28-day cycle for 3 cycles
====Subsequent treatment====
*WJTOG 9902, patients with CR or good PR: Prophylactic cranial irradiation
===References===
# WJTOG 9902: Saito H, Takada Y, Ichinose Y, Eguchi K, Kudoh S, Matsui K, Nakagawa K, Takada M, Negoro S, Tamura K, Ando M, Tada T, Fukuoka M; West Japan Thoracic Oncology Group. Phase II study of etoposide and cisplatin with concurrent twice-daily thoracic radiotherapy followed by irinotecan and cisplatin in patients with limited-disease small-cell lung cancer: West Japan Thoracic Oncology Group 9902. J Clin Oncol. 2006 Nov 20;24(33):5247-52. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
==Durvalumab monotherapy==
===Regimen===
Study 	Dates of enrollment 	Evidence 	Comparator 	Comparative Efficacy
Cheng et al. 2024 (ADRIATIC)	2018-09-28 to 2021-08-18	Phase 3 (E-RT-esc)	1. Placebo 	Seems to have longer OS (co-primary endpoint)Median OS: 55.9 vs 33.4 mo(HR 0.73, 98.21% CI 0.54-0.98)Seems to have longer PFS (co-primary endpoint)Median PFS: 16.6 vs 9.2 mo(HR 0.76, 97.195% CI 0.59-0.98)
Cheng et al. 2024 (ADRIATIC)	2018-09-28 to 2021-08-18	Phase 3 (E-RT-esc)	2. Durvalumab & Tremelimumab	Not directly compared
====Preceding treatment====
*Definitive chemoradiotherapy
====Immunotherapy====
*Durvalumab (Imfinzi) 1500 mg IV once on day 1
28-day cycle for 26 cycles (2 years)
===References===
#ADRIATIC: Cheng Y, Spigel DR, Cho BC, Laktionov KK, Fang J, Chen Y, Zenke Y, Lee KH, Wang Q, Navarro A, Bernabe R, Buchmeier EL, Chang JW, Shiraishi Y, Goksu SS, Badzio A, Shi A, Daniel DB, Hoa NTT, Zemanova M, Mann H, Gowda H, Jiang H, Senan S; ADRIATIC Investigators. Durvalumab after Chemoradiotherapy in Limited-Stage Small-Cell Lung Cancer. N Engl J Med. 2024 Oct 10;391(14):1313-1327. Epub 2024 Sep 13. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT03703297
==Radiation therapy==
===Regimen===
Study 	Dates of enrollment	Evidence
Evans et al. 1985	1981-1984 	Phase 2
====Preceding treatment====
*Induction EP x 6
====Radiotherapy====
*"Patients who did not have evidence of tumor spread beyond the mediastinum and/or ipsilateral supraclavicular notes" received thoracic radiation in 250 cGy fractions x 10 fractions (total dose: 2500 cGy)
===References===
# Evans WK, Shepherd FA, Feld R, Osoba D, Dang P, Deboer G. VP-16 and cisplatin as first-line therapy for small-cell lung cancer. J Clin Oncol. 1985 Nov;3(11):1471-7. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
# LLCG-STUDY-12: Lee SM, Woll PJ, Rudd R, Ferry D, O'Brien M, Middleton G, Spiro S, James L, Ali K, Jitlal M, Hackshaw A. Anti-angiogenic therapy using thalidomide combined with chemotherapy in small cell lung cancer: a randomized, double-blind, placebo-controlled trial. J Natl Cancer Inst. 2009 Aug 5;101(15):1049-57. Epub 2009 Jul 16. link to original article does not contain dosing details EuroPMC NCT00061919
==Whole brain irradiation==
PCI: Prophylactic Cranial Irradiation
===Regimen variant #1, 2000 cGy===
Study 	Dates of enrollment	Evidence
Cox et al. 1981 	1975-1978 	Non-randomized
Evans et al. 1985 	1981-1984 	Phase 2
Skarlos et al. 2001	1993-1999 	Non-randomized part of phase 2 RCT
Note: in Evans et al. 1985, the WB-XRT was given in-between cycles 3 & 4.
====Preceding treatment====
*Evans et al. 1985: Induction EP x 3
*Skarlos et al. 2001: Definitive EP & early HTRT versus EP & late HTRT
====Radiotherapy====
*Whole brain irradiation, 400 cGy fractions once per day x 5 fractions (total dose: 2000 cGy)
1-week course
====Subsequent treatment====
*Evans et al. 1985: EP consolidation x 3
===Regimen variant #2, 2400 cGy===
Study 	Dates of enrollment	Evidence
Takada et al. 2002 (JCOG 9104)	1991-1995 	Non-randomized part of phase 3 RCT
====Preceding treatment====
*Definitive EP & RT versus EP induction followed by definitive RT
====Radiotherapy====
*Whole brain irradiation, 150 cGy fractions given twice per day x 16 fractions (total dose: 2400 cGy)
2-week course
===Regimen variant #3, 2500 cGy===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Turrisi et al. 1999 (Intergroup 0096) 	1989-1992 	Non-randomized part of phase 3 RCT	 	
Le Péchoux et al. 2009 (PCI 99-01/EORTC 22003-08004/RTOG 0212/IFCT 99-01)	1999-2005 	Phase 3 (C) 	PCI x 3600 cGy	Did not meet primary endpoint of incidence of brain metastases at 2 years
Saito et al. 2006 (WJTOG 9902) 	2000-2002 	Phase 2 	 	
====Preceding treatment====
*Intergroup 0096: Definitive EP & once-daily RT versus EP & twice-daily RT
*WJTOG 9902: Definitive EP & RT, then IP consolidation x 3
====Radiotherapy====
*Whole brain irradiation, 250 cGy fractions x 10 fractions (total dose: 2500 cGy)
2-week course
===Regimen variant #4, 3000 cGy===
Study 	Dates of enrollment	Evidence
Sundstrøm et al. 2002	1989-1994 	Non-randomized part of phase 3 RCT
====Preceding treatment====
*Definitive CEV & RT versus EP & RT
====Radiotherapy====
*Whole brain irradiation, 200 cGy fractions once per day x 15 fractions (total dose: 3000 cGy)
3-week course
===References===
# Cox JD, Stanley K, Petrovich Z, Paig C, Yesner R. Cranial irradiation in cancer of the lung of all cell types. JAMA. 1981 Feb 6;245(5):469-72. link to original article EuroPMC
# Evans WK, Shepherd FA, Feld R, Osoba D, Dang P, Deboer G. VP-16 and cisplatin as first-line therapy for small-cell lung cancer. J Clin Oncol. 1985 Nov;3(11):1471-7. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
# Intergroup 0096: Turrisi AT 3rd, Kim K, Blum R, Sause WT, Livingston RB, Komaki R, Wagner H, Aisner S, Johnson DH. Twice-daily compared with once-daily thoracic radiotherapy in limited small-cell lung cancer treated concurrently with cisplatin and etoposide. N Engl J Med. 1999 Jan 28;340(4):265-71. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
# Meta-analysis: Aupérin A, Arriagada R, Pignon JP, Le Péchoux C, Gregor A, Stephens RJ, Kristjansen PE, Johnson BE, Ueoka H, Wagner H, Aisner J; Prophylactic Cranial Irradiation Overview Collaborative Group. Prophylactic cranial irradiation for patients with small-cell lung cancer in complete remission. N Engl J Med. 1999 Aug 12;341(7):476-84. link to original article EuroPMC
# JCOG 9104: Takada M, Fukuoka M, Kawahara M, Sugiura T, Yokoyama A, Yokota S, Nishiwaki Y, Watanabe K, Noda K, Tamura T, Fukuda H, Saijo N. Phase III study of concurrent versus sequential thoracic radiotherapy in combination with cisplatin and etoposide for limited-stage small-cell lung cancer: results of the Japan Clinical Oncology Group Study 9104. J Clin Oncol. 2002 Jul 15;20(14):3054-60. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC content property of HemOnc.org
# Sundstrøm S, Bremnes RM, Kaasa S, Aasebø U, Hatlevoll R, Dahle R, Boye N, Wang M, Vigander T, Vilsvik J, Skovlund E, Hannisdal E, Aamdal S; Norwegian Lung Cancer Study Group. Cisplatin and etoposide regimen is superior to cyclophosphamide, epirubicin, and vincristine regimen in small-cell lung cancer: results from a randomized phase III trial with 5 years' follow-up. J Clin Oncol. 2002 Dec 15;20(24):4665-72. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
# WJTOG 9902: Saito H, Takada Y, Ichinose Y, Eguchi K, Kudoh S, Matsui K, Nakagawa K, Takada M, Negoro S, Tamura K, Ando M, Tada T, Fukuoka M; West Japan Thoracic Oncology Group. Phase II study of etoposide and cisplatin with concurrent twice-daily thoracic radiotherapy followed by irinotecan and cisplatin in patients with limited-disease small-cell lung cancer: West Japan Thoracic Oncology Group 9902. J Clin Oncol. 2006 Nov 20;24(33):5247-52. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
# PCI 99-01/EORTC 22003-08004/RTOG 0212/IFCT 99-01: Le Péchoux C, Dunant A, Senan S, Wolfson A, Quoix E, Faivre-Finn C, Ciuleanu T, Arriagada R, Jones R, Wanders R, Lerouge D, Laplanche A; Prophylactic Cranial Irradiation (PCI) Collaborative Group. Standard-dose versus higher-dose prophylactic cranial irradiation (PCI) in patients with limited-stage small-cell lung cancer in complete remission after chemotherapy and thoracic radiotherapy (PCI 99-01, EORTC 22003-08004, RTOG 0212, and IFCT 99-01): a randomised clinical trial. Lancet Oncol. 2009 May;10(5):467-74. Epub 2009 Apr 20. link to original article EuroPMC NCT00005062
=Extensive stage, induction=
==Belotecan & Cisplatin==
BP: Belotecan and Platinol (Cisplatin)
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator	Comparative Efficacy
Oh et al. 2016 (COMBAT)	2009-2013 	Phase 3 (E-switch-ic)	EP; 60/100	Non-inferior RR (primary endpoint)
Note: the total number of planned cycles is not described in the manuscript; total duration information here was provided by the authors.
====Chemotherapy====
*Belotecan (Camptobell) 0.5 mg/m2 IV over 30 minutes once per day on days 1 to 4
*Cisplatin (Platinol) 60 mg/m2 IV once on day 1
21-day cycle for 4 to 8 cycles
===References===
# COMBAT: Oh IJ, Kim KS, Park CK, Kim YC, Lee KH, Jeong JH, Kim SY, Lee JE, Shin KC, Jang TW, Lee HK, Lee KY, Lee SY. Belotecan/cisplatin versus etoposide/cisplatin in previously untreated patients with extensive-stage small cell lung carcinoma: a multi-center randomized phase III trial. BMC Cancer. 2016 Aug 26;16:690. link to original article link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT00826644
==Carboplatin & Etoposide (CE)==
CE: Carboplatin & Etoposide
EP: Etoposide & Paraplatin (Carboplatin)
EC: Etoposide & Carboplatin
Ca/E: Carboplatin & Etoposide
===Regimen variant #1, AUC 4/600, PO etoposide===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Hermes et al. 2008	2001-2005 	Phase 3 (C)	Carboplatin & Irinotecan	Shorter OSMedian OS: 7.1 vs 8.5 mo(HR 1.41, 95% CI 1.06-1.89)
====Chemotherapy====
*Carboplatin (Paraplatin) AUC 4 (Chatelut formula) IV once on day 1
*Etoposide (Vepesid) 120 mg/m2 PO once per day on days 1 to 5
21-day cycle for 4 cycles
===Regimen variant #2, AUC 5/240===
Study 	Dates of enrollment 	Evidence 	Comparator 	Comparative Efficacy
Okamoto et al. 2007 (JCOG 9702)	1998-2004 	Phase 3 (E-switch-ic)	EP; split-dose	Did not meet primary endpoint of OS
Sekine et al. 2013 (D0702002) 	2006-07-04 to 2007-09-05	Phase 3 (C) 	Amrubicin 	Inconclusive whether non-inferior OS (primary endpoint)
====Chemotherapy====
*Carboplatin (Paraplatin) AUC 5 IV once on day 1
*Etoposide (Vepesid) 80 mg/m2 IV once per day on days 1 to 3
====Supportive therapy====
*JCOG 9702: G-CSF
21-day cycle for varying durations: 4 cycles (JCOG 9702); 4 to 6 cycles (D0702002)
===Regimen variant #3, AUC 5/300, 21-day cycles===
Study 	Dates of enrollment 	Evidence 	Comparator 	Comparative Efficacy
Socinski et al. 2009 (JMHO) 	2006-08 to 2007-12 	Phase 3 (C) 	Carboplatin & Pemetrexed 	Longer OS1 (primary endpoint)Median OS: 10.6 vs 8.1 mo(HR 0.64, 95% CI 0.52-0.79)
Spigel et al. 2011 (SALUTE) 	2007-2008 	Randomized Phase 2 (C) 	1a. CE & Bevacizumab1b. EP & Bevacizumab 	Seems to have shorter PFSMedian PFS: 4.4 vs 5.5 mo(HR 1.89, 95% CI 1.16-3.12)
Ready et al. 2015 (CALGB 30504) 	2007-2011 	Non-randomized part of phase 2 RCT	 	
Reck et al. 2016 (CA184-156) 	2012-2014 	Phase 3 (C) 	1a. CE & Ipilimumab1b. EP & Ipilimumab 	Did not meet primary endpoint of OSMedian OS: 10.9 vs 11 mo(HR 1.06, 95% CI 0.92-1.23)
Jalal et al. 2017 (MATISSE) 	2012-2013 	Randomized Phase 2 (C) 	PaCE 	Might have longer OSMedian OS: 10.37 vs 10.03 mo(HR 0.77, 95% CI 0.56-1.05)
Horn et al. 2018 (IMpower133) 	2016-06-06 to 2017-05-31	Phase 3 (C) 	CE & Atezolizumab 	Seems to have shorter OS2Median OS: 10.3 vs 12.3 mo(HR 1.32, 95% CI 1.05-1.67)
Paz-Ares et al. 2019 (CASPIAN) 	2017-03-27 to 2018-05-29	Phase 3 (C) 	1a. CE & Durvalumab1b. EP & Durvalumab 	Shorter OS3Median OS: 10.5 vs 12.9 mo(HR 1.33, 95% CI 1.10-1.61)
Rudin et al. 2020 (KEYNOTE-604) 	2017-05-15 to 2018-07-30	Phase 3 (C) 	1a. CE & Pembrolizumab1b. EP & Pembrolizumab	Seems to have shorter OSOS24: 11.2% vs 22.5%(HR 1.25, 95% CI 1.02-1.56)
Wang et al. 2022 (CAPSTONE-1) 	2018-2020 	Phase 3 (C) 	CE & Adebrelimab 	Shorter OS (primary endpoint)Median OS: 12.8 vs 15.3 mo(HR 1.39, 95% CI 1.11-1.72)
Cheng et al. 2024 (RATIONALE-312) 	2019-07-22 to 2021-04-21	Phase 3 (C) 	1a. CE & Tislelizumab1b. EP & Tislelizumab 	Shorter OSMedian OS: 13.5 vs 15.5 mo(HR 1.33, 95% CI 1.08-1.64)
Cheng et al. 2024 (ETER701) 	2020-03-18 to 2021-12-18	Phase 3 (C) 	1. CE & Anlotinib 	Did not meet co-primary endpoint of OSMedian OS: 11.9 vs 13.3 mo(HR 1.16, 95% CI 0.91-1.49)
Cheng et al. 2024 (ETER701) 	2020-03-18 to 2021-12-18	Phase 3 (C) 	2. CE, Anlotinib, Benmelstobart 	Shorter OS
Chen et al. 2025 (ZKAB001-LEES-2020-07)	2021-07-15 to 2022-05-12	Phase 3 (C) 	CE & Socazolimab 	Seems to have shorter OS (primary endpoint)Median OS: 11.58 vs 13.9 mo(HR 1.25, 95% CI 1.02-1.53)
1JMHO was designed as a non-inferiority trial; however, the control arm was found to have longer OS.
2Reported efficacy for IMpower133 is based on the 2020 update.
3Reported efficacy for CASPIAN is based on the 2021 update.
Note: CASPIAN gave a range of dosing; see paper for details.
====Chemotherapy====
*Carboplatin (Paraplatin) AUC 5 IV once on day 1
*Etoposide (Vepesid) 100 mg/m2 IV once per day on days 1 to 3
====Supportive therapy====
*Socinksi et al. 2009: "supportive therapies, such as erythropoietic agents or granulocyte colony-stimulating factors, were administered according to the American Society of Clinical Oncology guidelines"
21-day cycle for varying durations: 4 cycles (CASPIAN, CA184-156, ETER701, IMpower133, KEYNOTE-604, RATIONALE-312, SALUTE); 4 to 6 cycles (CALGB 30504, CAPSTONE-1, MATISSE); 6 cycles (JMHO)
====Subsequent treatment====
*CALGB 30504, SD or better: Observation versus sunitinib maintenance
===Regimen variant #4, AUC 5/300, 28-day cycles===
Study 	Dates of enrollment	Evidence
Okamoto et al. 1999	1995-1996 	Phase 2
Quoix et al. 2001 	1997-1999 	Phase 2
====Eligibility criteria====
*At least 70 years old
====Chemotherapy====
*Carboplatin (Paraplatin) AUC 5 IV over 60 minutes once on day 1, given first
*Etoposide (Vepesid) 100 mg/m2 IV over 60 minutes once per day on days 1 to 3, given second
====Supportive therapy====
*Dexamethasone (Decadron) 8 mg IV once per day on days 1 to 3, prior to chemotherapy
*Granisetron 40 mcg/kg IV once per day on days 1 to 3, prior to chemotherapy
*Okamoto et al. 1999: G-CSF (type not specified) 2 mcg/kg SC given for grade 3 or greater leukopenia/neutropenia
*Quiox et al. 2001: "Haematopoietic growth factors were allowed as prophylactic or curative treatment only if grade 4 neutropenia greater than 7 days occurred"
28-day cycle for varying durations: 4 cycles (Okamoto et al. 1999); 6 cycles (Quoix et al. 2001)
====Subsequent treatment====
*Palliative radiation therapy was allowed to control persistent pain from bony metastases
===Regimen variant #5, AUC 5/360===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Seckl et al. 2017 (LUNGSTAR)	2007-2012 	Phase 3 (C)	1a. CE & Pravastatin1b. EP & Pravastatin	Did not meet primary endpoint of OSOS24: 14.1% vs 13.2%(HR 0.99, 95% CI 0.86-1.14)
====Chemotherapy====
*Carboplatin (Paraplatin) AUC 5 IV once on day 1
*Etoposide (Vepesid) 120 mg/m2 IV once per day on days 1 to 3
21-day cycle for 6 cycles
===Regimen variant #6, AUC 5/420===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Heigener et al. 2009 	2000-2003 	Phase 3 (C) 	CE; dose-intense	Did not meet primary endpoint of OS
Schmittel et al. 2006	2002-2008 	Randomized Phase 2 (E-switch-ic)	IP 	Might have shorter OS (secondary endpoint)
====Chemotherapy====
*Carboplatin (Paraplatin) AUC 5 IV over 60 minutes once on day 1 
*Etoposide (Vepesid) 140 mg/m2 IV over 90 minutes once per day on days 1 to 3
====Supportive therapy====
*5-HT3 antagonist IV once per day on days 1 to 3, prior to chemotherapy
*Loperamide (Imodium) 4 mg PO prn first episode of diarrhea, then 2 mg PO Q2H until diarrhea stops
21- to 28-day cycle for up to 6 cycles
===Regimen variant #7, AUC 5/440, 1 day of oral etoposide per cycle===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Lee et al. 2009 (LLCG-STUDY-12)	2003-2006 	Phase 3 (C)	CE & Thalidomide 	Did not meet primary endpoint of OSMedian OS: 10.5 vs 10.1 mo(HR 0.92, 95% CI 0.79-1.08)
Seckl et al. 2017 (LUNGSTAR) 	2007-2012 	Phase 3 (C)	1a. CE & Pravastatin1b. EP & Pravastatin	Did not meet primary endpoint of OSOS24: 14.1% vs 13.2%(HR 0.99, 95% CI 0.86-1.14)
====Chemotherapy====
*Carboplatin (Paraplatin) AUC 5 IV once on day 1
*Etoposide (Vepesid) 120 mg/m2 IV once per day on days 1 & 2, then 100 mg PO twice per day on day 3
21-day cycle for up to 6 cycles
===Regimen variant #8, AUC 5/520, 2 days of oral etoposide per cycle===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Lee et al. 2009 (LLCG-STUDY-12)	2003-2006 	Phase 3 (C)	CE & Thalidomide 	Did not meet primary endpoint of OSMedian OS: 10.5 vs 10.1 mo(HR 0.92, 95% CI 0.79-1.08)
Seckl et al. 2017 (LUNGSTAR) 	2007-2012 	Phase 3 (C)	1a. CE & Pravastatin1b. EP & Pravastatin	Did not meet primary endpoint of OSOS24: 14.1% vs 13.2%(HR 0.99, 95% CI 0.86-1.14)
====Chemotherapy====
*Carboplatin (Paraplatin) AUC 5 IV once on day 1
*Etoposide (Vepesid) 120 mg/m2 IV once on day 1, then 100 mg PO twice per day on days 2 & 3
21-day cycle for up to 6 cycles
===Regimen variant #9, AUC 6/360===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Seckl et al. 2017 (LUNGSTAR)	2007-2012 	Phase 3 (C)	1a. CE & Pravastatin1b. EP & Pravastatin	Did not meet primary endpoint of OSOS24: 14.1% vs 13.2%(HR 0.99, 95% CI 0.86-1.14)
====Chemotherapy====
*Carboplatin (Paraplatin) AUC 6 IV once on day 1
*Etoposide (Vepesid) 120 mg/m2 IV once per day on days 1 to 3
21-day cycle for 6 cycles
===Regimen variant #10, AUC 6/440, 1 day of oral etoposide per cycle===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Seckl et al. 2017 (LUNGSTAR)	2007-2012 	Phase 3 (C)	1a. CE & Pravastatin1b. EP & Pravastatin	Did not meet primary endpoint of OSOS24: 14.1% vs 13.2%(HR 0.99, 95% CI 0.86-1.14)
====Chemotherapy====
*Carboplatin (Paraplatin) AUC 6 IV once on day 1
*Etoposide (Vepesid) 120 mg/m2 IV once per day on days 1 & 2, then 100 mg PO twice per day on day 3
21-day cycle for up to 6 cycles
===Regimen variant #11, AUC 6/520, 2 days of oral etoposide per cycle===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Seckl et al. 2017 (LUNGSTAR)	2007-2012 	Phase 3 (C)	1a. CE & Pravastatin1b. EP & Pravastatin	Did not meet primary endpoint of OSOS24: 14.1% vs 13.2%(HR 0.99, 95% CI 0.86-1.14)
====Chemotherapy====
*Carboplatin (Paraplatin) AUC 6 IV once on day 1
*Etoposide (Vepesid) 120 mg/m2 IV once on day 1, then 100 mg PO twice per day on days 2 & 3
21-day cycle for up to 6 cycles
===References===
# Okamoto H, Watanabe K, Nishiwaki Y, Mori K, Kurita Y, Hayashi I, Masutani M, Nakata K, Tsuchiya S, Isobe H, Saijo N. Phase II study of area under the plasma-concentration-versus-time curve-based carboplatin plus standard-dose intravenous etoposide in elderly patients with small-cell lung cancer. J Clin Oncol. 1999 Nov;17(11):3540-5. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
# Quoix E, Breton JL, Daniel C, Jacoulet P, Debieuvre D, Paillot N, Kessler R, Moreau L, Coëtmeur D, Lemarié E, Milleron B. Etoposide phosphate with carboplatin in the treatment of elderly patients with small-cell lung cancer: a phase II study. Ann Oncol. 2001 Jul;12(7):957-62. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
# Schmittel A, Fischer von Weikersthal L, Sebastian M, Martus P, Schulze K, Hortig P, Reeb M, Thiel E, Keilholz U. A randomized phase II trial of irinotecan plus carboplatin versus etoposide plus carboplatin treatment in patients with extended disease small-cell lung cancer. Ann Oncol. 2006 Apr;17(4):663-7. Epub 2006 Jan 19. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
## Update: Schmittel A, Sebastian M, Fischer von Weikersthal L, Martus P, Gauler TC, Kaufmann C, Hortig P, Fischer JR, Link H, Binder D, Fischer B, Caca K, Eberhardt WE, Keilholz U; Arbeitsgemeinschaft Internistische Onkologie Thoracic Oncology Study Group. A German multicenter, randomized phase III trial comparing irinotecan-carboplatin with etoposide-carboplatin as first-line therapy for extensive-disease small-cell lung cancer. Ann Oncol. 2011 Aug;22(8):1798-804. Epub 2011 Jan 25. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
# JCOG 9702: Okamoto H, Watanabe K, Kunikane H, Yokoyama A, Kudoh S, Asakawa T, Shibata T, Kunitoh H, Tamura T, Saijo N. Randomised phase III trial of carboplatin plus etoposide vs split doses of cisplatin plus etoposide in elderly or poor-risk patients with extensive disease small-cell lung cancer: JCOG 9702. Br J Cancer. 2007 Jul 16;97(2):162-9. Epub 2007 Jun 19. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors EuroPMC
# Hermes A, Bergman B, Bremnes R, Ek L, Fluge S, Sederholm C, Sundstrøm S, Thaning L, Vilsvik J, Aasebø U, Sörenson S. Irinotecan plus carboplatin versus oral etoposide plus carboplatin in extensive small-cell lung cancer: a randomized phase III trial. J Clin Oncol. 2008 Sep 10;26(26):4261-7. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
# Heigener DF, Manegold C, Jäger E, Saal JG, Zuna I, Gatzemeier U. Multicenter randomized open-label phase III study comparing efficacy, safety, and tolerability of conventional carboplatin plus etoposide versus dose-intensified carboplatin plus etoposide plus lenograstim in small-cell lung cancer in "extensive disease" stage. Am J Clin Oncol. 2009 Feb;32(1):61-4. link to original article dosing details in abstract have been reviewed by our editors EuroPMC
# LLCG-STUDY-12: Lee SM, Woll PJ, Rudd R, Ferry D, O'Brien M, Middleton G, Spiro S, James L, Ali K, Jitlal M, Hackshaw A. Anti-angiogenic therapy using thalidomide combined with chemotherapy in small cell lung cancer: a randomized, double-blind, placebo-controlled trial. J Natl Cancer Inst. 2009 Aug 5;101(15):1049-57. Epub 2009 Jul 16. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT00061919
# JMHO: Socinski MA, Smit EF, Lorigan P, Konduri K, Reck M, Szczesna A, Blakely J, Serwatowski P, Karaseva NA, Ciuleanu T, Jassem J, Dediu M, Hong S, Visseren-Grul C, Hanauske AR, Obasaju CK, Guba SC, Thatcher N. Phase III study of pemetrexed plus carboplatin compared with etoposide plus carboplatin in chemotherapy-naive patients with extensive-stage small-cell lung cancer. J Clin Oncol. 2009 Oct 1;27(28):4787-92. Epub 2009 Aug 31. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT00363415
# SALUTE: Spigel DR, Townley PM, Waterhouse DM, Fang L, Adiguzel I, Huang JE, Karlin DA, Faoro L, Scappaticci FA, Socinski MA. Randomized phase II study of bevacizumab in combination with chemotherapy in previously untreated extensive-stage small-cell lung cancer: results from the SALUTE trial. J Clin Oncol. 2011 Jun 1;29(16):2215-22. Epub 2011 Apr 18. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT00403403
# D0702002: Sekine I, Okamoto H, Horai T, Nakagawa K, Ohmatsu H, Yokoyama A, Katakami N, Shibuya M, Saijo N, Fukuoka M. A randomized phase III study of single-agent amrubicin vs carboplatin/etoposide in elderly patients with extensive-disease small-cell lung cancer. Clin Lung Cancer. 2014 Mar;15(2):96-102. Epub 2013 Nov 14. link to original article dosing details in abstract have been reviewed by our editors EuroPMC NCT00286169
# CALGB 30504: Ready NE, Pang HH, Gu L, Otterson GA, Thomas SP, Miller AA, Baggstrom M, Masters GA, Graziano SL, Crawford J, Bogart J, Vokes EE. Chemotherapy with or without maintenance sunitinib for untreated extensive-stage small-cell lung cancer: A randomized, double-blind, placebo-controlled phase II study-CALGB 30504 (Alliance). J Clin Oncol. 2015 May 20;33(15):1660-5. Epub 2015 Mar 2. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors EuroPMC NCT00453154
# CA184-156: Reck M, Luft A, Szczesna A, Havel L, Kim SW, Akerley W, Pietanza MC, Wu YL, Zielinski C, Thomas M, Felip E, Gold K, Horn L, Aerts J, Nakagawa K, Lorigan P, Pieters A, Kong Sanchez T, Fairchild J, Spigel D. Phase III randomized trial of ipilimumab plus etoposide and platinum versus placebo plus etoposide and platinum in extensive-stage small-cell lung cancer. J Clin Oncol. 2016 Nov 1;34(31):3740-3748. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT01450761
# LUNGSTAR: Seckl MJ, Ottensmeier CH, Cullen M, Schmid P, Ngai Y, Muthukumar D, Thompson J, Harden S, Middleton G, Fife KM, Crosse B, Taylor P, Nash S, Hackshaw A. Multicenter, phase III, randomized, double-blind, placebo-controlled trial of pravastatin added to first-line standard chemotherapy in small-cell lung cancer (LUNGSTAR). J Clin Oncol. 2017 May 10;35(14):1506-1514. Epub 2017 Feb 27. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article EuroPMC NCT00433498
# MATISSE: Jalal SI, Lavin P, Lo G, Lebel F, Einhorn L. Carboplatin and etoposide with or without palifosfamide in untreated extensive-stage small-cell lung cancer: A multicenter, adaptive, randomized phase III study (MATISSE). J Clin Oncol. 2017 Aug 10;35(23):2619-2623. Epub 2017 Jun 12. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT01555710
# IMpower133: Horn L, Mansfield AS, Szczęsna A, Havel L, Krzakowski M, Hochmair MJ, Huemer F, Losonczy G, Johnson ML, Nishio M, Reck M, Mok T, Lam S, Shames DS, Liu J, Ding B, Lopez-Chavez A, Kabbinavar F, Lin W, Sandler A, Liu SV; IMpower133 Study Group. First-line atezolizumab plus chemotherapy in extensive-stage small-cell lung cancer. N Engl J Med. 2018 Dec 6;379(23):2220-2229. Epub 2018 Sep 25. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT02763579
##PRO analysis: Mansfield AS, Każarnowicz A, Karaseva N, Sánchez A, De Boer R, Andric Z, Reck M, Atagi S, Lee JS, Garassino M, Liu SV, Horn L, Wen X, Quach C, Yu W, Kabbinavar F, Lam S, Morris S, Califano R. Safety and patient-reported outcomes of atezolizumab, carboplatin, and etoposide in extensive-stage small-cell lung cancer (IMpower133): a randomized phase I/III trial. Ann Oncol. 2020 Feb;31(2):310-317. Epub 2019 Dec 9. link to original article EuroPMC
## Update: Liu SV, Reck M, Mansfield AS, Mok T, Scherpereel A, Reinmuth N, Garassino MC, De Castro Carpeno J, Califano R, Nishio M, Orlandi F, Alatorre-Alexander J, Leal T, Cheng Y, Lee JS, Lam S, McCleland M, Deng Y, Phan S, Horn L. Updated Overall Survival and PD-L1 Subgroup Analysis of Patients With Extensive-Stage Small-Cell Lung Cancer Treated With Atezolizumab, Carboplatin, and Etoposide (IMpower133). J Clin Oncol. 2021 Feb 20;39(6):619-630. Epub 2021 Jan 13. link to original article link to PMC article EuroPMC
# CASPIAN: Paz-Ares L, Dvorkin M, Chen Y, Reinmuth N, Hotta K, Trukhin D, Statsenko G, Hochmair MJ, Özgüroğlu M, Ji JH, Voitko O, Poltoratskiy A, Ponce S, Verderame F, Havel L, Bondarenko I, Kazarnowicz A, Losonczy G, Conev NV, Armstrong J, Byrne N, Shire N, Jiang H, Goldman JW; CASPIAN investigators. Durvalumab plus platinum-etoposide versus platinum-etoposide in first-line treatment of extensive-stage small-cell lung cancer (CASPIAN): a randomised, controlled, open-label, phase 3 trial. Lancet. 2019 Nov 23;394(10212):1929-1939. Epub 2019 Oct 4. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT03043872
##PRO analysis: Goldman JW, Garassino MC, Chen Y, Özgüroğlu M, Dvorkin M, Trukhin D, Statsenko G, Hotta K, Ji JH, Hochmair MJ, Voitko O, Havel L, Poltoratskiy A, Losonczy G, Reinmuth N, Patel N, Laud PJ, Shire N, Jiang H, Paz-Ares L. Patient-reported outcomes with first-line durvalumab plus platinum-etoposide versus platinum-etoposide in extensive-stage small-cell lung cancer (CASPIAN): a randomized, controlled, open-label, phase III study. Lung Cancer. 2020 Nov;149:46-52. Epub 2020 Sep 10. link to original article EuroPMC
##Update: Goldman JW, Dvorkin M, Chen Y, Reinmuth N, Hotta K, Trukhin D, Statsenko G, Hochmair MJ, Özgüroğlu M, Ji JH, Garassino MC, Voitko O, Poltoratskiy A, Ponce S, Verderame F, Havel L, Bondarenko I, Każarnowicz A, Losonczy G, Conev NV, Armstrong J, Byrne N, Thiyagarajah P, Jiang H, Paz-Ares L; CASPIAN investigators. Durvalumab, with or without tremelimumab, plus platinum-etoposide versus platinum-etoposide alone in first-line treatment of extensive-stage small-cell lung cancer (CASPIAN): updated results from a randomised, controlled, open-label, phase 3 trial. Lancet Oncol. 2021 Jan;22(1):51-65. Epub 2020 Dec 4. link to original article EuroPMC
# KEYNOTE-604: Rudin CM, Awad MM, Navarro A, Gottfried M, Peters S, Csőszi T, Cheema PK, Rodriguez-Abreu D, Wollner M, Yang JC, Mazieres J, Orlandi FJ, Luft A, Gümüş M, Kato T, Kalemkerian GP, Luo Y, Ebiana V, Pietanza MC, Kim HR; KEYNOTE-604 Investigators. Pembrolizumab or Placebo Plus Etoposide and Platinum as First-Line Therapy for Extensive-Stage Small-Cell Lung Cancer: Randomized, Double-Blind, Phase III KEYNOTE-604 Study. J Clin Oncol. 2020 Jul 20;38(21):2369-2379. Epub 2020 May 29. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors EuroPMC NCT03066778
##PRO analysis: Kim HR, Awad MM, Navarro A, Gottfried M, Peters S, Csőszi T, Cheema PK, Rodriguez-Abreu D, Wollner M, Yang JC, Mazieres J, Orlandi FJ, Luft A, Gümüş M, Kato T, Kalemkerian GP, Luo Y, Santorelli ML, Pietanza MC, Rudin CM. Patient-Reported Health-Related Quality of Life in KEYNOTE-604: Pembrolizumab or Placebo Added to Etoposide and Platinum as First-Line Therapy for Extensive-Stage SCLC. JTO Clin Res Rep. 2023 Sep 9;4(11):100572. link to original article link to PMC article EuroPMC
# CAPSTONE-1: Wang J, Zhou C, Yao W, Wang Q, Min X, Chen G, Xu X, Li X, Xu F, Fang Y, Yang R, Yu G, Gong Y, Zhao J, Fan Y, Liu Q, Cao L, Yao Y, Liu Y, Li X, Wu J, He Z, Lu K, Jiang L, Hu C, Zhao W, Zhang B, Shi W, Zhang X, Cheng Y; CAPSTONE-1 Study Group. Adebrelimab or placebo plus carboplatin and etoposide as first-line treatment for extensive-stage small-cell lung cancer (CAPSTONE-1): a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2022 Jun;23(6):739-747. Epub 2022 May 13. link to original article dosing details in abstract have been reviewed by our editors EuroPMC NCT03711305
#RATIONALE-312: Cheng Y, Fan Y, Zhao Y, Huang D, Li X, Zhang P, Kang M, Yang N, Zhong D, Wang Z, Yu Y, Zhang Y, Zhao J, Qin T, Chen C, Leaw S, Zheng W, Song Y; RATIONALE-312 Study Group. Tislelizumab Plus Platinum and Etoposide Versus Placebo Plus Platinum and Etoposide as First-Line Treatment for Extensive-Stage SCLC (RATIONALE-312): A Multicenter, Double-Blind, Placebo-Controlled, Randomized, Phase 3 Clinical Trial. J Thorac Oncol. 2024 Jul;19(7):1073-1085. Epub 2024 Mar 7. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT04005716
#ETER701: Cheng Y, Chen J, Zhang W, Xie C, Hu Q, Zhou N, Huang C, Wei S, Sun H, Li X, Yu Y, Lai J, Yang H, Fang H, Chen H, Zhang P, Gu K, Wang Q, Shi J, Yi T, Xu X, Ye X, Wang D, Xie C, Liu C, Zheng Y, Lin D, Zhuang W, Lu P, Yu G, Li J, Gu Y, Li B, Wu R, Jiang O, Wang Z, Wu G, Lin H, Zhong D, Xu Y, Shu Y, Wu D, Chen X, Wang J, Wang M, Yang R. Benmelstobart, anlotinib and chemotherapy in extensive-stage small-cell lung cancer: a randomized phase 3 trial. Nat Med. 2024 Oct;30(10):2967-2976. Epub 2024 Jul 11. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors EuroPMC NCT04234607
#ZKAB001-LEES-2020-07: Chen Z, Chen J, Huang D, Zhang W, Wu L, Yi T, Wang Q, Han L, Tan L, Li Y, Zhang Z, Li N, Li J, Zhang T, Hu Y, Sun H, Wu Y, He Z, Yang R, Cheng P, Li X, Shi J, Yu G, Ma D, Li BX, Dai X, Wong M, Li Y, Yu X, Lu S; Socazolimab Study Group. A multicenter, randomized, double-blind, placebo-controlled phase 3 study of Socazolimab or placebo combined with carboplatin and etoposide in the first-line treatment of extensive-stage small cell lung cancer. Signal Transduct Target Ther. 2025 Jan 13;10(1):28. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors EuroPMC NCT04878016
==Carboplatin & Etoposide (CE) & Atezolizumab==
CE & Atezolizumab: Carboplatin, Etoposide, Atezolizumab
===Regimen===
Study 	Dates of enrollment 	Evidence 	Comparator 	Comparative Efficacy
Horn et al. 2018 (IMpower133) 	2016-06-06 to 2017-05-31	Phase 3 (E-RT-esc)	CE 	Seems to have longer OS1 (co-primary endpoint)Median OS: 12.3 vs 10.3 mo(HR 0.76, 95% CI 0.60-0.95)
Rudin et al. 2023 (SKYSCRAPER-02)	2020-02 to 2021-03 	Phase 3 (C) 	CE, Atezolizumab, Tiragolumab	Did not meet co-primary endpoints of PFS/OS
1Reported efficacy for IMpower133 is based on the 2020 update.
====Chemotherapy====
*Carboplatin (Paraplatin) as follows:
**Cycles 1 to 4: AUC 5 IV once on day 1
*Etoposide (Vepesid) as follows:
**Cycles 1 to 4: 100 mg/m2 IV once per day on days 1 to 3
====Immunotherapy====
*Atezolizumab (Tecentriq) 1200 mg IV once on day 1
21-day cycles
===References===
# IMpower133: Horn L, Mansfield AS, Szczęsna A, Havel L, Krzakowski M, Hochmair MJ, Huemer F, Losonczy G, Johnson ML, Nishio M, Reck M, Mok T, Lam S, Shames DS, Liu J, Ding B, Lopez-Chavez A, Kabbinavar F, Lin W, Sandler A, Liu SV; IMpower133 Study Group. First-line atezolizumab plus chemotherapy in extensive-stage small-cell lung cancer. N Engl J Med. 2018 Dec 6;379(23):2220-2229. Epub 2018 Sep 25. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT02763579
##PRO analysis: Mansfield AS, Każarnowicz A, Karaseva N, Sánchez A, De Boer R, Andric Z, Reck M, Atagi S, Lee JS, Garassino M, Liu SV, Horn L, Wen X, Quach C, Yu W, Kabbinavar F, Lam S, Morris S, Califano R. Safety and patient-reported outcomes of atezolizumab, carboplatin, and etoposide in extensive-stage small-cell lung cancer (IMpower133): a randomized phase I/III trial. Ann Oncol. 2020 Feb;31(2):310-317. Epub 2019 Dec 9. link to original article EuroPMC
## Update: Liu SV, Reck M, Mansfield AS, Mok T, Scherpereel A, Reinmuth N, Garassino MC, De Castro Carpeno J, Califano R, Nishio M, Orlandi F, Alatorre-Alexander J, Leal T, Cheng Y, Lee JS, Lam S, McCleland M, Deng Y, Phan S, Horn L. Updated Overall Survival and PD-L1 Subgroup Analysis of Patients With Extensive-Stage Small-Cell Lung Cancer Treated With Atezolizumab, Carboplatin, and Etoposide (IMpower133). J Clin Oncol. 2021 Feb 20;39(6):619-630. Epub 2021 Jan 13. link to original article link to PMC article EuroPMC
#SKYSCRAPER-02: Rudin CM, Liu SV, Soo RA, Lu S, Hong MH, Lee JS, Bryl M, Dumoulin DW, Rittmeyer A, Chiu CH, Ozyilkan O, Johnson M, Navarro A, Novello S, Ozawa Y, Tam SH, Patil NS, Wen X, Huang M, Hoang T, Meng R, Reck M. SKYSCRAPER-02: Tiragolumab in Combination With Atezolizumab Plus Chemotherapy in Untreated Extensive-Stage Small-Cell Lung Cancer. J Clin Oncol. 2024 Jan 20;42(3):324-335. Epub 2023 Nov 17. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article EuroPMC NCT04256421
#IMforte: NCT05091567
==Carboplatin & Etoposide (CE) & Bevacizumab==
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Spigel et al. 2011 (SALUTE)	2007-2008 	Randomized Phase 2 (E-esc)	1a. CE1b. EP	Seems to have longer PFS (primary endpoint)Median PFS: 5.5 vs 4.4 mo(HR 0.53, 95% CI 0.32-0.86)
====Chemotherapy====
*Carboplatin (Paraplatin) AUC 5 IV once on day 1
*Etoposide (Vepesid) 100 mg/m2 IV once per day on days 1 to 3
====Targeted therapy====
*Bevacizumab (Avastin) 15 mg/kg IV once on day 1
21-day cycle for 4 cycles
====Subsequent treatment====
*Bevacizumab maintenance
===References===
# SALUTE: Spigel DR, Townley PM, Waterhouse DM, Fang L, Adiguzel I, Huang JE, Karlin DA, Faoro L, Scappaticci FA, Socinski MA. Randomized phase II study of bevacizumab in combination with chemotherapy in previously untreated extensive-stage small-cell lung cancer: results from the SALUTE trial. J Clin Oncol. 2011 Jun 1;29(16):2215-22. Epub 2011 Apr 18. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT00403403
==Carboplatin & Etoposide (CE) & Durvalumab==
===Regimen===
Study 	Dates of enrollment 	Evidence 	Comparator 	Comparative Efficacy
Paz-Ares et al. 2019 (CASPIAN)	2017-03-27 to 2018-05-29	Phase 3 (E-RT-esc)	1a. CE1b. EP	Longer OS1 (primary endpoint)Median OS: 12.9 vs 10.5 mo(HR 0.75, 95% CI 0.62-0.91)
1Reported efficacy is based on the 2021 update.
====Chemotherapy====
*Carboplatin (Paraplatin) as follows:
**Cycles 1 to 4: AUC 5 to 6 IV once on day 1
*Etoposide (Vepesid) as follows:
**Cycles 1 to 4: 80 to 100 mg/m2 IV once per day on days 1 to 3
====Immunotherapy====
*Durvalumab (Imfinzi) as follows:
**Cycles 1 to 4: 1500 mg IV once on day 1
**Cycle 5 onwards: 1500 mg IV once on day 1
21-day cycle for 4 cycles, then 28-day cycles
===References===
# CASPIAN: Paz-Ares L, Dvorkin M, Chen Y, Reinmuth N, Hotta K, Trukhin D, Statsenko G, Hochmair MJ, Özgüroğlu M, Ji JH, Voitko O, Poltoratskiy A, Ponce S, Verderame F, Havel L, Bondarenko I, Kazarnowicz A, Losonczy G, Conev NV, Armstrong J, Byrne N, Shire N, Jiang H, Goldman JW; CASPIAN investigators. Durvalumab plus platinum-etoposide versus platinum-etoposide in first-line treatment of extensive-stage small-cell lung cancer (CASPIAN): a randomised, controlled, open-label, phase 3 trial. Lancet. 2019 Nov 23;394(10212):1929-1939. Epub 2019 Oct 4. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT03043872
##PRO analysis: Goldman JW, Garassino MC, Chen Y, Özgüroğlu M, Dvorkin M, Trukhin D, Statsenko G, Hotta K, Ji JH, Hochmair MJ, Voitko O, Havel L, Poltoratskiy A, Losonczy G, Reinmuth N, Patel N, Laud PJ, Shire N, Jiang H, Paz-Ares L. Patient-reported outcomes with first-line durvalumab plus platinum-etoposide versus platinum-etoposide in extensive-stage small-cell lung cancer (CASPIAN): a randomized, controlled, open-label, phase III study. Lung Cancer. 2020 Nov;149:46-52. Epub 2020 Sep 10. link to original article EuroPMC
##Update: Goldman JW, Dvorkin M, Chen Y, Reinmuth N, Hotta K, Trukhin D, Statsenko G, Hochmair MJ, Özgüroğlu M, Ji JH, Garassino MC, Voitko O, Poltoratskiy A, Ponce S, Verderame F, Havel L, Bondarenko I, Każarnowicz A, Losonczy G, Conev NV, Armstrong J, Byrne N, Thiyagarajah P, Jiang H, Paz-Ares L; CASPIAN investigators. Durvalumab, with or without tremelimumab, plus platinum-etoposide versus platinum-etoposide alone in first-line treatment of extensive-stage small-cell lung cancer (CASPIAN): updated results from a randomised, controlled, open-label, phase 3 trial. Lancet Oncol. 2021 Jan;22(1):51-65. Epub 2020 Dec 4. link to original article EuroPMC
==Carboplatin & Etoposide (CE) & Serplulimab==
===Regimen===
Study 	Dates of enrollment 	Evidence 	Comparator	Comparative Efficacy
Cheng et al. 2022 (ASTRUM-005)	2019-09-12 to 2021-04-27	Phase 3 (E-RT-esc)	CE 	Longer OS (primary endpoint)Median OS: 15.4 vs 10.9 mo(HR 0.63, 95% CI 0.49-0.82)
Note: the original capped dose of carboplatin was 800 mg; this was modified in a protocol amendment.
====Chemotherapy====
*Carboplatin (Paraplatin) as follows:
**Cycles 1 to 4: AUC 5 (maximum dose of 750 mg) IV once on day 1
*Etoposide (Vepesid) as follows:
**Cycles 1 to 4: 100 mg/m2 IV once per day on days 1 to 3
====Immunotherapy====
*Serplulimab (Hansizhuang) 4.5 mg/kg IV once on day 1
21-day cycles
===References===
#ASTRUM-005: Cheng Y, Han L, Wu L, Chen J, Sun H, Wen G, Ji Y, Dvorkin M, Shi J, Pan Z, Shi J, Wang X, Bai Y, Melkadze T, Pan Y, Min X, Viguro M, Li X, Zhao Y, Yang J, Makharadze T, Arkania E, Kang W, Wang Q, Zhu J; ASTRUM-005 Study Group. Effect of First-Line Serplulimab vs Placebo Added to Chemotherapy on Survival in Patients With Extensive-Stage Small Cell Lung Cancer: The ASTRUM-005 Randomized Clinical Trial. JAMA. 2022 Sep 27;328(12):1223-1232. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article EuroPMC NCT04063163
==Carboplatin & Etoposide (CE) & Tislelizumab==
===Regimen===
Study 	Dates of enrollment 	Evidence 	Comparator 	Comparative Efficacy
Cheng et al. 2024 (RATIONALE-312)	2019-07-22 to 2021-04-21	Phase 3 (E-esc)	1a. CE1b. EP	Longer OS (primary endpoint)Median OS: 15.5 vs 13.5 mo(HR 0.75, 95% CI 0.61-0.93)
====Chemotherapy====
*Carboplatin (Paraplatin) as follows:
**Cycles 1 to 4: AUC 5 IV once on day 1
*Etoposide (Vepesid) as follows:
**Cycles 1 to 4: 100 mg/m2 IV once per day on days 1 to 3
====Immunotherapy====
*Tislelizumab (Baizean) 200 mg IV once on day 1
21-day cycles
===References===
#RATIONALE-312: Cheng Y, Fan Y, Zhao Y, Huang D, Li X, Zhang P, Kang M, Yang N, Zhong D, Wang Z, Yu Y, Zhang Y, Zhao J, Qin T, Chen C, Leaw S, Zheng W, Song Y; RATIONALE-312 Study Group. Tislelizumab Plus Platinum and Etoposide Versus Placebo Plus Platinum and Etoposide as First-Line Treatment for Extensive-Stage SCLC (RATIONALE-312): A Multicenter, Double-Blind, Placebo-Controlled, Randomized, Phase 3 Clinical Trial. J Thorac Oncol. 2024 Jul;19(7):1073-1085. Epub 2024 Mar 7. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT04005716
==Carboplatin & Irinotecan==
IC: Irinotecan & Carboplatin
IP: Irinotecan & Paraplatin (Carboplatin)
===Regimen variant #1, AUC 4/175===
Study 	Dates of enrollment	Evidence 	Comparator	Comparative Efficacy
Hermes et al. 2008	2001-2005 	Phase 3 (E-switch-ic)	CE 	Longer OS (primary endpoint)Median OS: 8.5 vs 7.1 mo(HR 0.71, 95% CI 0.53-0.94)
====Chemotherapy====
*Carboplatin (Paraplatin) AUC 4 (Chatelut formula) IV once on day 1
*Irinotecan (Camptosar) 175 mg/m2 IV once on day 1
21-day cycle for 4 cycles
===Regimen variant #2, AUC 5/150===
Study 	Dates of enrollment	Evidence 	Comparator	Comparative Efficacy
Schmittel et al. 2006	2002-2008 	Randomized Phase 2 (E-switch-ic)	CE 	Might have longer OS (secondary endpoint)
====Chemotherapy====
*Carboplatin (Paraplatin) AUC 5 IV over 60 minutes once on day 1 
*Irinotecan (Camptosar) 50 mg/m2 IV over 30 minutes once per day on days 1, 8, 15
====Supportive therapy====
*5-HT3 antagonist IV once per day on days 1, 8, 15, prior to chemotherapy
*Loperamide (Imodium) 4 mg PO prn first episode of diarrhea, then 2 mg PO Q2H until diarrhea stops
28-day cycle for up to 6 cycles
===References===
# Schmittel A, Fischer von Weikersthal L, Sebastian M, Martus P, Schulze K, Hortig P, Reeb M, Thiel E, Keilholz U. A randomized phase II trial of irinotecan plus carboplatin versus etoposide plus carboplatin treatment in patients with extended disease small-cell lung cancer. Ann Oncol. 2006 Apr;17(4):663-7. Epub 2006 Jan 19. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
## Update: Schmittel A, Sebastian M, Fischer von Weikersthal L, Martus P, Gauler TC, Kaufmann C, Hortig P, Fischer JR, Link H, Binder D, Fischer B, Caca K, Eberhardt WE, Keilholz U; Arbeitsgemeinschaft Internistische Onkologie Thoracic Oncology Study Group. A German multicenter, randomized phase III trial comparing irinotecan-carboplatin with etoposide-carboplatin as first-line therapy for extensive-disease small-cell lung cancer. Ann Oncol. 2011 Aug;22(8):1798-804. Epub 2011 Jan 25. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
# Hermes A, Bergman B, Bremnes R, Ek L, Fluge S, Sederholm C, Sundstrøm S, Thaning L, Vilsvik J, Aasebø U, Sörenson S. Irinotecan plus carboplatin versus oral etoposide plus carboplatin in extensive small-cell lung cancer: a randomized phase III trial. J Clin Oncol. 2008 Sep 10;26(26):4261-7. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
==Carboplatin & Paclitaxel (CP) & Ipilimumab==
===Regimen variant #1, phased ipilimumab===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Reck et al. 2012 (CA184-041SCLC)	2008-2009 	Randomized Phase 2 (E-esc)	1. CP 	Seems to have longer irPFS (primary endpoint)
Reck et al. 2012 (CA184-041SCLC)	2008-2009 	Randomized Phase 2 (E-esc)	2. CP & Ipilimumab; concurrent Ipilimumab	Not reported
====Chemotherapy====
*Carboplatin (Paraplatin) AUC 6 IV once on day 1
*Paclitaxel (Taxol) 175 mg/m2 IV once on day 1
====Immunotherapy====
*Ipilimumab (Yervoy) as follows:
**Cycles 3 to 6: 10 mg/kg IV once on day 1
21-day cycle for up to 6 cycles 
====Subsequent treatment====
*Ipilimumab maintenance
===Regimen variant #2, concurrent ipilimumab===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Reck et al. 2012 (CA184-041SCLC)	2008-2009 	Randomized Phase 2 (E-esc)	1. CP 	Did not meet secondary endpoints
Reck et al. 2012 (CA184-041SCLC)	2008-2009 	Randomized Phase 2 (E-esc)	2. CP & Ipilimumab; phased Ipilimumab	Not reported
Note: all efficacy endpoints in the ED-SCLC cohort were secondary.
====Chemotherapy====
*Carboplatin (Paraplatin) AUC 6 IV once on day 1
*Paclitaxel (Taxol) 175 mg/m2 IV once on day 1
====Immunotherapy====
*Ipilimumab (Yervoy) as follows:
**Cycles 1 to 4: 10 mg/kg IV once on day 1
21-day cycle for up to 6 cycles 
====Subsequent treatment====
*Ipilimumab maintenance
===References===
# CA184-041SCLC: Reck M, Bondarenko I, Luft A, Serwatowski P, Barlesi F, Chacko R, Sebastian M, Lu H, Cuillerot JM, Lynch TJ. Ipilimumab in combination with paclitaxel and carboplatin as first-line therapy in extensive-disease-small-cell lung cancer: results from a randomized, double-blind, multicenter phase 2 trial. Ann Oncol. 2013 Jan;24(1):75-83. Epub 2012 Aug 2. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT00527735
==Cisplatin & Etoposide (EP)==
EP: Etoposide and Platinol (Cisplatin)
PE: Platinol (Cisplatin) and Etoposide
===Regimen variant #1, 60/300===
Study 	Dates of enrollment	Evidence 	Comparator	Comparative Efficacy
Oh et al. 2016 (COMBAT)	2009-2013 	Phase 3 (C)	BP 	Non-inferior RR
Note: the total number of planned cycles is not described in the manuscript; total duration information here was provided by the authors.
====Chemotherapy====
*Cisplatin (Platinol) 60 mg/m2 IV once on day 1
*Etoposide (Vepesid) 100 mg/m2 IV once per day on days 1 to 3
21-day cycle for 4 to 8 cycles
===Regimen variant #2, 60/360===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Hanna et al. 2006 	2000-2003 	Phase 3 (C)	Cisplatin & Irinotecan 	Did not meet primary endpoint of OS
Seckl et al. 2017 (LUNGSTAR)	2007-2012 	Phase 3 (C)	1a. CE & Pravastatin1b. EP & Pravastatin	Did not meet primary endpoint of OSOS24: 14.1% vs 13.2%(HR 0.99, 95% CI 0.86-1.14)
====Chemotherapy====
*Cisplatin (Platinol) 60 mg/m2 IV once on day 1 
*Etoposide (Vepesid) 120 mg/m2 IV once per day on days 1 to 3
====Supportive therapy====
*Per Hanna et al. 2006:
**G-CSF used according to 1999 American Society of Clinical Oncology guidelines
**"Erythropoietin was allowed at the discretion of the treating physician."
21-day cycle for 4 to 6 cycles
===Regimen variant #3, 60/440, 1 day of oral etoposide per cycle===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Seckl et al. 2017 (LUNGSTAR)	2007-2012 	Phase 3 (C)	1a. CE & Pravastatin1b. EP & Pravastatin	Did not meet primary endpoint of OSOS24: 14.1% vs 13.2%(HR 0.99, 95% CI 0.86-1.14)
====Chemotherapy====
*Cisplatin (Platinol) 60 mg/m2 IV once on day 1
*Etoposide (Vepesid) 120 mg/m2 IV once per day on days 1 & 2, then 100 mg PO twice per day on day 3
21-day cycle for up to 6 cycles
===Regimen variant #4, 60/520, 2 days of oral etoposide per cycle===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Seckl et al. 2017 (LUNGSTAR)	2007-2012 	Phase 3 (C)	1a. CE & Pravastatin1b. EP & Pravastatin	Did not meet primary endpoint of OSOS24: 14.1% vs 13.2%(HR 0.99, 95% CI 0.86-1.14)
====Chemotherapy====
*Cisplatin (Platinol) 60 mg/m2 IV once on day 1
*Etoposide (Vepesid) 120 mg/m2 IV once on day 1, then 100 mg PO twice per day on days 2 & 3
21-day cycle for up to 6 cycles
===Regimen variant #5, 70/300, q3wk===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Kim et al. 2018 (CRCST-L-0001)	2006-2011 	Phase 3 (C)	Cisplatin & Irinotecan	Did not meet primary endpoint of OS
====Chemotherapy====
*Cisplatin (Platinol) 70 mg/m2 IV once on day 1 
*Etoposide (Vepesid) 100 mg/m2 IV once per day on days 1 to 3
21-day cycle for up to 6 cycles
===Regimen variant #6, 70/300, q4wk===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Ruotsalainen et al. 1999	1990-05 to 1994-11 	Phase 3 (C)	EP & IFN-alpha	Did not meet endpoint of OS50%
====Chemotherapy====
*Cisplatin (Platinol) 70 mg/m2 IV once on day 1 
*Etoposide (Vepesid) 100 mg/m2 IV once per day on days 1 to 3
28-day cycle for 6 cycles
===Regimen variant #7, 75/240, split cisplatin===
Study 	Dates of enrollment	Evidence 	Comparator	Comparative Efficacy
Okamoto et al. 2007 (JCOG 9702)	1998-2004 	Phase 3 (C)	CE 	Did not meet primary endpoint of OS
====Chemotherapy====
*Cisplatin (Platinol) 25 mg/m2 IV once per day on days 1 to 3
*Etoposide (Vepesid) 80 mg/m2 IV once per day on days 1 to 3
21- to 28-day cycle for 4 cycles
===Regimen variant #8, 75/300===
Study 	Dates of enrollment 	Evidence 	Comparator 	Comparative Efficacy
Fink et al. 2012 (GSK 104864-A/479)	2002-2006 	Phase 3 (C) 	1. Cisplatin & Topotecan 	Non-inferior OS
Fink et al. 2012 (GSK 104864-A/479)	2002-2006 	Phase 3 (C) 	2. Etoposide & Topotecan 	Not reported
Spigel et al. 2011 (SALUTE) 	2007-2008 	Randomized Phase 2 (C)	1a. CE & Bevacizumab1b. EP & Bevacizumab 	Seems to have shorter PFSMedian PFS: 4.4 vs 5.5 mo(HR 1.89, 95% CI 1.16-3.12)
Reck et al. 2016 (CA184-156) 	2012-2014 	Phase 3 (C) 	1a. CE & Ipilimumab1b. EP & Ipilimumab 	Did not meet primary endpoint of OSMedian OS: 10.9 vs 11 mo(HR 1.06, 95% CI 0.92-1.23)
Rudin et al. 2020 (KEYNOTE-604) 	2017-05-15 to 2018-07-30	Phase 3 (C) 	1a. CE & Pembrolizumab1b. EP & Pembrolizumab	Seems to have shorter OSOS24: 11.2% vs 22.5%(HR 1.25, 95% CI 1.02-1.56)
Cheng et al. 2024 (RATIONALE-312) 	2019-07-22 to 2021-04-21	Phase 3 (C) 	1a. CE & Tislelizumab1b. EP & Tislelizumab 	Shorter OSMedian OS: 13.5 vs 15.5 mo(HR 1.33, 95% CI 1.08-1.64)
Cheng et al. 2024 (EXTENTORCH) 	2019-09-26 to 2021-05-20	Phase 3 (C) 	EP & Toripalimab 	Seems to have shorter OS (co-primary endpoint)Median OS: 13.3 vs 14.6 mo(HR 1.25, 95% CI 1.02-1.54)Shorter PFS (co-primary endpoint)Median PFS: 5.6 vs 5.8 mo(HR 1.49, 95% CI 1.22-1.85)
====Chemotherapy====
*Cisplatin (Platinol) 75 mg/m2 IV once on day 1
*Etoposide (Vepesid) 100 mg/m2 IV once per day on days 1 to 3
21-day cycle for varying durations: 4 cycles (KEYNOTE-604, RATIONALE-312, SALUTE); 4 to 6 cycles (EXTENTORCH); 6 cycles (CA184-156, GSK 104864-A/479)
===Regimen variant #9, 75/300, split cisplatin===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Evans et al. 1985 	1981-1984 	Phase 2 	 	
Tiseo et al. 2017 (GOIRC-AIFA FARM6PMFJM)	2009-2015 	Phase 3 (C)	EP & Bevacizumab	Did not meet primary endpoint of OSMedian OS: 9.8 vs 8.9 mo(HR 1.28, 95% CI 0.94-1.72)
Note: in Evans et al. 1985, patients with disease responding to therapy received prophylactic cranial irradiation, 400 cGy fractions given daily x 5 fractions (total dose: 2000 cGy) over 5 days between cycles 3 and 4; Locoregional radiation therapy was only used if symptoms persisted after 6 cycles of treatment: Radiation therapy, 250 cGy/rad fractions x 10 fractions (total dose: 2500 cGy/rad), given after cycle 6 of chemotherapy.
====Chemotherapy====
*Cisplatin (Platinol) 25 mg/m2 IV slow push once per day on days 1 to 3, given second
*Etoposide (Vepesid) 100 mg/m2 IV over at least 30 minutes once per day on days 1 to 3, given first
====Supportive therapy====
*Dexamethasone (Decadron) 10 mg IV once per day on days 1 to 3, prior to chemotherapy
*Metoclopramide (Reglan) 10 mg IV or PO once per day on days 1 to 3, prior to chemotherapy
*Prochlorperazine (Compazine) 10 mg IM or PO once per day on days 1 to 3, prior to chemotherapy
*"No special efforts were made to hydrate the patients," though PO fluid intake was encouraged, and 500 mL normal saline was given with etoposide infusion.
21- to 28-day cycle for up to 6 cycles
===Regimen variant #10, 75/390, split cisplatin===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Miller et al. 1995	1990-1993 	Phase 3 (C)	EP; oral etoposide	Did not meet primary endpoint of OS
====Chemotherapy====
*Cisplatin (Platinol) 25 mg/m2 IV over 60 minutes once per day on days 1 to 3
*Etoposide (Vepesid) 130 mg/m2 IV over 60 minutes once per day on days 1 to 3
21-day cycle for 8 cycles
===Regimen variant #11, 75/700, 3 days of oral etoposide per cycle===
Study 	Dates of enrollment	Evidence 	Comparator	Comparative Efficacy
Sundstrøm et al. 2002	1989-1994 	Phase 3 (E-switch-ic)	CEV 	Did not meet primary endpoint of OS
Note: Patients in Sundstrøm et al. 2002 with extensive stage disease did not routinely receive radiation therapy. "However, chest or cranial irradiation was optional if severe symptoms could not be palliated by chemotherapy." Oral etoposide to be taken on an empty stomach.
====Chemotherapy====
*Cisplatin (Platinol) 75 mg/m2 IV once on day 1 
*Etoposide (Vepesid) 100 mg/m2 IV once on day 1, then 200 mg/m2 PO once per day on days 2 to 4
====Supportive therapy====
*"Standard prehydration and posthydration procedures were followed in conjunction with cisplatin administration."
21-day cycle for up to 5 cycles
===Regimen variant #12, 80/240===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Ihde et al. 1994 	1983-1991 	Phase 3 (C)	EP; high-dose	Did not meet primary endpoint of CR rate
Niell et al. 2005 (CALGB 9732)	1998-2001 	Phase 3 (C)	PET 	Did not meet endpoints of FFS50%/OS50%
Note: Concurrent radiation therapy with the start of chemotherapy was given to patients with brain metastases, epidural metastases, and impending pathologic bone fractures.
====Chemotherapy====
*Cisplatin (Platinol) 80 mg/m2 IV once on day 1 
*Etoposide (Vepesid) 80 mg/m2 IV once per day on days 1 to 3
====Supportive therapy====
*"Half-normal saline was infused for 2 to 6 hours with cisplatin, usually in conjunction with a diuretic."
*Corticosteroids were usually given for patients receiving radiation therapy for brain and epidural metastases.
21-day cycle for 4 to 8 cycles
====CNS therapy====
*Patients with carcinomatous meningitis received Methotrexate (MTX) IT (dose/schedule not specified) and radiation to functionally compromised areas of the CNS
====Subsequent treatment====
*Ihde et al. 1994, CR after 4 cycles: EP continuation x 4 cycles. Some patients were randomized to receive prophylactic cranial irradiation. Radiation could also be given at the patient's request. No details about dose/schedule given.
*Ihde et al. 1994, PR, no response, or progressive disease: Salvage CAV or "an individualized 3-drug in vitro-selected regimen (IVSR) during cycles 5 to 8 if drug-sensitivity testing data were available."
===Regimen variant #13, 80/300===
Study 	Dates of enrollment 	Evidence 	Comparator 	Comparative Efficacy
Fukuoka et al. 1991 (JCOG8502) 	1985-1988 	Phase 3 (C) 	1. CAV 	Not reported
Fukuoka et al. 1991 (JCOG8502) 	1985-1988 	Phase 3 (C) 	2. CAV/PE 	Might have shorter OS
Miyamoto et al. 1992 	Not reported in abstract	Phase 3 (C) 	PEI 	Did not meet primary endpoint of OS
Noda et al. 2002 (JCOG 9511) 	1995-1998 	Phase 3 (C) 	IP 	Shorter OSMedian OS: 9.4 vs 12.8 mo(HR 1.67, 95% CI 1.20-2.33)
Eckardt et al. 2006 (GSK 104864-A/389)	2001-2003 	Phase 3 (C) 	Cisplatin & Topotecan 	Non-inferior OS
Lara et al. 2009 (SWOG S0124) 	2002-2007 	Phase 3 (C) 	IP 	Did not meet primary endpoint of OS
Zatloukal et al. 2010 	2003-2007 	Phase 3 (C) 	IP 	Non-inferior OSMedian OS: 9.7 vs 10.2 mo(HR 1.23, 95% CI 0.99-1.54)
Ready et al. 2015 (CALGB 30504) 	2007-2011 	Non-randomized part of phase 2 RCT	 	
Sun et al. 2016 (D0750018) 	2008-2010 	Phase 3 (C) 	Amrubicin & Cisplatin 	Inconclusive whether non-inferior OS (primary endpoint)Median OS: 10.3 vs 11.8 mo
Morabito et al. 2017 (STAD-1) 	2008-04-10 to 2014-12-24	Phase 3 (C) 	EP; toxicity-adjusted dosing	Did not meet primary endpoint of ORRORR: 54.4% vs 58.2%
Note: The full manuscript for Miyamoto et al. 1992 was not available for review.
====Chemotherapy====
*Cisplatin (Platinol) 80 mg/m2 IV once on day 1
*Etoposide (Vepesid) 100 mg/m2 IV once per day on days 1 to 3
**Alternative scheduling: JCOG8502 & Miyamoto et al. 1992 gave etoposide on days 1, 3, 5
====Supportive therapy====
*"Hydration and administration of antiemetic drugs."
21-day cycle for varying durations: 4 cycles (JCOG 9511, SWOG S0124); 4 to 6 cycles (CALGB 30504, D0750018, GSK 104864-A/389); 6 cycles (STAD-1, Zatloukal et al. 2010); 17 cycles (JCOG8502)
====Subsequent treatment====
*Baka et al. 2010: Topotecan consolidation x 4
*CALGB 30504, SD or better: Observation versus sunitinib maintenance
===Regimen variant #14, 80/360===
Study 	Dates of enrollment	Evidence 	Comparator	Comparative Efficacy
Thatcher et al. 2005 (MRC LU21)	1996-03 to 2002-02 	Phase 3 (C)	ICE-V 	Shorter OSMedian OS: 11.6 vs 15.6 mo(HR 1.35, 95% CI 1.10-1.67)
====Chemotherapy====
*Cisplatin (Platinol) 80 mg/m2 IV once on day 1
*Etoposide (Vepesid) 120 mg/m2 IV once per day on days 2 & 3, then 240 mg/m2 PO once on day 3
21-day cycle for 6 cycles
===Regimen variant #15, 80/400, split cisplatin===
Study 	Dates of enrollment	Evidence 	Comparator	Comparative Efficacy
Loehrer et al. 1995	1989-1993 	Phase 3 (C)	VIP 	Seems to have shorter OS
====Chemotherapy====
*Cisplatin (Platinol) 20 mg/m2 IV once per day on days 1 to 4
*Etoposide (Vepesid) 100 mg/m2 IV once per day on days 1 to 4
21-day cycle for 4 cycles
===Regimen variant #16, 80/600, 2 days of oral etoposide per cycle===
Study 	Dates of enrollment	Evidence 	Comparator	Comparative Efficacy
Baka et al. 2008	1999-2005 	Phase 3 (E-switch-ic)	ACE 	Did not meet primary endpoint of OS12
====Chemotherapy====
*Cisplatin (Platinol) 80 mg/m2 IV once on day 1
*Etoposide (Vepesid) 120 mg/m2 IV once on day 1, then 240 mg/m2/day PO on days 2 & 3
21-day cycle for 6 cycles
===Regimen variant #17, 100/300, q3wk===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Artal-Cortés et al. 2004	1994-1998 	Phase 3 (C)	Cisplatin & Epirubicin	Did not meet primary endpoint of OS
====Chemotherapy====
*Cisplatin (Platinol) 100 mg/m2 IV once on day 2
*Etoposide (Vepesid) 100 mg/m2 IV once per day on days 1 to 3
21-day cycle for 6 cycles
===Regimen variant #18, 100/300, q4wk===
Study 	Dates of enrollment	Evidence 	Comparator	Comparative Efficacy
Pujol et al. 2001 (FNCLCC 95012)	1996-1999 	Phase 3 (C)	PCDE 	Shorter OS
====Chemotherapy====
*Cisplatin (Platinol) 100 mg/m2 IV once on day 2
*Etoposide (Vepesid) 100 mg/m2 IV once per day on days 1 to 3
28-day cycle for 6 cycles
===Regimen variant #19, 100/400, split cisplatin===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Roth et al. 1992 	1985-1989 	Phase 3 (C) 	1. CAV2. CAV/PE 	Did not meet primary endpoint of OS50%
Hainsworth et al. 1995	1992-1993 	Randomized Phase 2 (E-RT-switch-ic)	Cisplatin & Etoposide phosphate	Not compared
====Chemotherapy====
*Cisplatin (Platinol) 20 mg/m2 IV once per day on days 1 to 5
*Etoposide (Vepesid) 80 mg/m2 IV once per day on days 1 to 5
21-day cycle for varying durations: 4 cycles (Roth et al. 1992); indefinitely (Hainsworth et al. 1995)
===References===
# Evans WK, Shepherd FA, Feld R, Osoba D, Dang P, Deboer G. VP-16 and cisplatin as first-line therapy for small-cell lung cancer. J Clin Oncol. 1985 Nov;3(11):1471-7. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
# JCOG8502: Fukuoka M, Furuse K, Saijo N, Nishiwaki Y, Ikegami H, Tamura T, Shimoyama M, Suemasu K. Randomized trial of cyclophosphamide, doxorubicin, and vincristine versus cisplatin and etoposide versus alternation of these regimens in small-cell lung cancer. J Natl Cancer Inst. 1991 Jun 19;83(12):855-61. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
# Miyamoto H, Nakabayashi T, Isobe H, Akita H, Kawakami Y, Arimoto T, Asakawa M, Suzuki A, Fujikane T, Shimizu T, Sakai E. A phase III comparison of etoposide/cisplatin with or without added ifosfamide in small-cell lung cancer. Oncology. 1992;49(6):431-5. link to original article dosing details in abstract have been reviewed by our editors EuroPMC
# Roth BJ, Johnson DH, Einhorn LH, Schacter LP, Cherng NC, Cohen HJ, Crawford J, Randolph JA, Goodlow JL, Broun GO, Omura GA, Greco FA; Southeastern Cancer Study Group. Randomized study of cyclophosphamide, doxorubicin, and vincristine versus etoposide and cisplatin versus alternation of these two regimens in extensive small-cell lung cancer: a phase III trial of the Southeastern Cancer Study Group. J Clin Oncol. 1992 Feb;10(2):282-91. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
# Ihde DC, Mulshine JL, Kramer BS, Steinberg SM, Linnoila RI, Gazdar AF, Edison M, Phelps RM, Lesar M, Phares JC, Grayson J, Minna JD, Johnson BE. Prospective randomized comparison of high-dose and standard-dose etoposide and cisplatin chemotherapy in patients with extensive-stage small-cell lung cancer. J Clin Oncol. 1994 Oct;12(10):2022-34. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
# Hainsworth JD, Levitan N, Wampler GL, Belani CP, Seyedsadr MS, Randolph J, Schacter LP, Greco FA. Phase II randomized study of cisplatin plus etoposide phosphate or etoposide in the treatment of small-cell lung cancer. J Clin Oncol. 1995 Jun;13(6):1436-42. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
# Miller AA, Herndon JE 2nd, Hollis DR, Ellerton J, Langleben A, Richards F 2nd, Green MR; CALGB. Schedule dependency of 21-day oral versus 3-day intravenous etoposide in combination with intravenous cisplatin in extensive-stage small-cell lung cancer: a randomized phase III study of the Cancer and Leukemia Group B. J Clin Oncol. 1995 Aug;13(8):1871-9. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
# Loehrer PJ Sr, Ansari R, Gonin R, Monaco F, Fisher W, Sandler A, Einhorn LH; Hoosier Oncology Group. Cisplatin plus etoposide with and without ifosfamide in extensive small-cell lung cancer: a Hoosier Oncology Group study. J Clin Oncol. 1995 Oct;13(10):2594-9. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
# Ruotsalainen TM, Halme M, Tamminen K, Szopinski J, Niiranen A, Pyrhönen S, Riska H, Maasilta P, Jekunen A, Mäntylä M, Kajanti M, Joensuu H, Sarna S, Cantell K, Mattson K. Concomitant chemotherapy and IFN-alpha for small cell lung cancer: a randomized multicenter phase III study. J Interferon Cytokine Res. 1999 Mar;19(3):253-9. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
# FNCLCC 95012: Pujol JL, Daurès JP, Rivière A, Quoix E, Westeel V, Quantin X, Breton JL, Lemarié E, Poudenx M, Milleron B, Moro D, Debieuvre D, Le Chevalier T. Etoposide plus cisplatin with or without the combination of 4'-epidoxorubicin plus cyclophosphamide in treatment of extensive small-cell lung cancer: a French Federation of Cancer Institutes multicenter phase III randomized study. J Natl Cancer Inst. 2001 Feb 21;93(4):300-8. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT00003606
# JCOG 9511: Noda K, Nishiwaki Y, Kawahara M, Negoro S, Sugiura T, Yokoyama A, Fukuoka M, Mori K, Watanabe K, Tamura T, Yamamoto S, Saijo N; JCOG. Irinotecan plus cisplatin compared with etoposide plus cisplatin for extensive small-cell lung cancer. N Engl J Med. 2002 Jan 10;346(2):85-91. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
# Sundstrøm S, Bremnes RM, Kaasa S, Aasebø U, Hatlevoll R, Dahle R, Boye N, Wang M, Vigander T, Vilsvik J, Skovlund E, Hannisdal E, Aamdal S; Norwegian Lung Cancer Study Group. Cisplatin and etoposide regimen is superior to cyclophosphamide, epirubicin, and vincristine regimen in small-cell lung cancer: results from a randomized phase III trial with 5 years' follow-up. J Clin Oncol. 2002 Dec 15;20(24):4665-72. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
# Artal-Cortés A, Gomez-Codina J, Gonzalez-Larriba JL, Barneto I, Carrato A, Isla D, Camps C, Garcia-Giron C, Font A, Meana A, Lomas M, Vadell C, Arrivi A, Alonso C, Maestu I, Campbell J, Rosell R. Prospective randomized phase III trial of etoposide/cisplatin versus high-dose epirubicin/cisplatin in small-cell lung cancer. Clin Lung Cancer. 2004 Nov;6(3):175-83. link to original article dosing details in abstract have been reviewed by our editors EuroPMC
# CALGB 9732: Niell HB, Herndon JE 2nd, Miller AA, Watson DM, Sandler AB, Kelly K, Marks RS, Perry MC, Ansari RH, Otterson G, Ellerton J, Vokes EE, Green MR; CALGB. Randomized phase III intergroup trial of etoposide and cisplatin with or without paclitaxel and granulocyte colony-stimulating factor in patients with extensive-stage small-cell lung cancer: Cancer and Leukemia Group B Trial 9732. J Clin Oncol. 2005 Jun 1;23(16):3752-9. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT00003299
#MRC LU21: Thatcher N, Qian W, Clark PI, Hopwood P, Sambrook RJ, Owens R, Stephens RJ, Girling DJ. Ifosfamide, carboplatin, and etoposide with midcycle vincristine versus standard chemotherapy in patients with small-cell lung cancer and good performance status: clinical and quality-of-life results of the British Medical Research Council multicenter randomized LU21 trial. J Clin Oncol. 2005 Nov 20;23(33):8371-9. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT00002822
# Hanna N, Bunn PA Jr, Langer C, Einhorn L, Guthrie T Jr, Beck T, Ansari R, Ellis P, Byrne M, Morrison M, Hariharan S, Wang B, Sandler A. Randomized phase III trial comparing irinotecan/cisplatin with etoposide/cisplatin in patients with previously untreated extensive-stage disease small-cell lung cancer. J Clin Oncol. 2006 May 1;24(13):2038-43. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
# GSK 104864-A/389: Eckardt JR, von Pawel J, Papai Z, Tomova A, Tzekova V, Crofts TE, Brannon S, Wissel P, Ross G. Open-label, multicenter, randomized, phase III study comparing oral topotecan/cisplatin versus etoposide/cisplatin as treatment for chemotherapy-naive patients with extensive-disease small-cell lung cancer. J Clin Oncol. 2006 May 1;24(13):2044-51. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT00043927
# JCOG 9702: Okamoto H, Watanabe K, Kunikane H, Yokoyama A, Kudoh S, Asakawa T, Shibata T, Kunitoh H, Tamura T, Saijo N. Randomised phase III trial of carboplatin plus etoposide vs split doses of cisplatin plus etoposide in elderly or poor-risk patients with extensive disease small-cell lung cancer: JCOG 9702. Br J Cancer. 2007 Jul 16;97(2):162-9. Epub 2007 Jun 19. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors EuroPMC
# Baka S, Califano R, Ferraldeschi R, Aschroft L, Thatcher N, Taylor P, Faivre-Finn C, Blackhall F, Lorigan P. Phase III randomised trial of doxorubicin-based chemotherapy compared with platinum-based chemotherapy in small-cell lung cancer. Br J Cancer. 2008 Aug 5;99(3):442-7. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors EuroPMC
# SWOG S0124: Lara PN Jr, Natale R, Crowley J, Lenz HJ, Redman MW, Carleton JE, Jett J, Langer CJ, Kuebler JP, Dakhil SR, Chansky K, Gandara DR. Phase III trial of irinotecan/cisplatin compared with etoposide/cisplatin in extensive-stage small-cell lung cancer: clinical and pharmacogenomic results from SWOG S0124. J Clin Oncol. 2009 May 20;27(15):2530-5. Epub 2009 Apr 6. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors EuroPMC NCT00045162
# Zatloukal P, Cardenal F, Szczesna A, Gorbunova V, Moiseyenko V, Zhang X, Cisar L, Soria JC, Domine M, Thomas M. A multicenter international randomized phase III study comparing cisplatin in combination with irinotecan or etoposide in previously untreated small-cell lung cancer patients with extensive disease. Ann Oncol. 2010 Sep;21(9):1810-6. Epub 2010 Mar 15. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT00143455
# SALUTE: Spigel DR, Townley PM, Waterhouse DM, Fang L, Adiguzel I, Huang JE, Karlin DA, Faoro L, Scappaticci FA, Socinski MA. Randomized phase II study of bevacizumab in combination with chemotherapy in previously untreated extensive-stage small-cell lung cancer: results from the SALUTE trial. J Clin Oncol. 2011 Jun 1;29(16):2215-22. Epub 2011 Apr 18. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT00403403
# GSK 104864-A/479: Fink TH, Huber RM, Heigener DF, Eschbach C, Waller C, Steinhauer EU, Virchow JC, Eberhardt F, Schweisfurth H, Schroeder M, Ittel T, Hummler S, Banik N, Bogenrieder T, Acker T, Wolf M; “Aktion Bronchialkarzinom” (ABC Study Group). Topotecan/cisplatin compared with cisplatin/etoposide as first-line treatment for patients with extensive disease small-cell lung cancer: final results of a randomized phase III trial. J Thorac Oncol. 2012 Sep;7(9):1432-9. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT00320359
# CALGB 30504: Ready NE, Pang HH, Gu L, Otterson GA, Thomas SP, Miller AA, Baggstrom M, Masters GA, Graziano SL, Crawford J, Bogart J, Vokes EE. Chemotherapy with or without maintenance sunitinib for untreated extensive-stage small-cell lung cancer: A randomized, double-blind, placebo-controlled phase II study-CALGB 30504 (Alliance). J Clin Oncol. 2015 May 20;33(15):1660-5. Epub 2015 Mar 2. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors EuroPMC NCT00453154
# D0750018: Sun Y, Cheng Y, Hao X, Wang J, Hu C, Han B, Liu X, Zhang L, Wan H, Xia Z, Liu Y, Li W, Hou M, Zhang H, Xiu Q, Zhu Y, Feng J, Qin S, Luo X. Randomized phase III trial of amrubicin/cisplatin versus etoposide/cisplatin as first-line treatment for extensive small-cell lung cancer. BMC Cancer. 2016 Apr 9;16:265. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors EuroPMC NCT00660504
# COMBAT: Oh IJ, Kim KS, Park CK, Kim YC, Lee KH, Jeong JH, Kim SY, Lee JE, Shin KC, Jang TW, Lee HK, Lee KY, Lee SY. Belotecan/cisplatin versus etoposide/cisplatin in previously untreated patients with extensive-stage small cell lung carcinoma: a multi-center randomized phase III trial. BMC Cancer. 2016 Aug 26;16:690. link to original article link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT00826644
# CA184-156: Reck M, Luft A, Szczesna A, Havel L, Kim SW, Akerley W, Pietanza MC, Wu YL, Zielinski C, Thomas M, Felip E, Gold K, Horn L, Aerts J, Nakagawa K, Lorigan P, Pieters A, Kong Sanchez T, Fairchild J, Spigel D. Phase III randomized trial of ipilimumab plus etoposide and platinum versus placebo plus etoposide and platinum in extensive-stage small-cell lung cancer. J Clin Oncol. 2016 Nov 1;34(31):3740-3748. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT01450761
# GOIRC-AIFA FARM6PMFJM: Tiseo M, Boni L, Ambrosio F, Camerini A, Baldini E, Cinieri S, Brighenti M, Zanelli F, Defraia E, Chiari R, Dazzi C, Tibaldi C, Turolla GM, D'Alessandro V, Zilembo N, Trolese AR, Grossi F, Riccardi F, Ardizzoni A. Italian, multicenter, phase III, randomized study of cisplatin plus etoposide with or without bevacizumab as first-line treatment in extensive-disease small-cell lung cancer: the GOIRC-AIFA FARM6PMFJM trial. J Clin Oncol. 2017 Apr 20;35(12):1281-1287. Epub 2017 Jan 30. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC EudraCT 2007-007949-13
# LUNGSTAR: Seckl MJ, Ottensmeier CH, Cullen M, Schmid P, Ngai Y, Muthukumar D, Thompson J, Harden S, Middleton G, Fife KM, Crosse B, Taylor P, Nash S, Hackshaw A. Multicenter, phase III, randomized, double-blind, placebo-controlled trial of pravastatin added to first-line standard chemotherapy in small-cell lung cancer (LUNGSTAR). J Clin Oncol. 2017 May 10;35(14):1506-1514. Epub 2017 Feb 27. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article EuroPMC NCT00433498
#STAD-1: Morabito A, Daniele G, Costanzo R, Favaretto AG, Filipazzi V, Rossi A, Gebbia V, Castiglione F, Cavanna L, Maiello E, Sandomenico C, Bonanno L, Piazza E, Maione P, Piccirillo MC, Di Maio M, Rocco G, Gallo C, Perrone F, Gridelli C. A multicenter, randomized, phase 3 trial comparing fixed dose versus toxicity-adjusted dose of cisplatin + etoposide in extensive small-cell lung cancer (SCLC) patients: The Small-cell-lung cancer Toxicity Adjusted Dosing (STAD-1) trial. Lung Cancer. 2017 Jun;108:15-21. Epub 2017 Feb 27. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT00526396
# CRCST-L-0001: Kim DW, Kim HG, Kim JH, Park K, Kim HK, Jang JS, Kim BS, Kang JH, Lee KH, Kim SW, Ryoo HM, Kim JS, Lee KH, Kwon JH, Choi JH, Shin SW, Hahn S, Heo DS. Randomized phase III trial of irinotecan plus cisplatin versus etoposide plus cisplatin in chemotherapy-naïve Korean patients with extensive-disease small cell lung cancer. Cancer Res Treat. 2019 Jan;51(1):119-127. Epub 2018 Mar 12. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors EuroPMC NCT00349492
# KEYNOTE-604: Rudin CM, Awad MM, Navarro A, Gottfried M, Peters S, Csőszi T, Cheema PK, Rodriguez-Abreu D, Wollner M, Yang JC, Mazieres J, Orlandi FJ, Luft A, Gümüş M, Kato T, Kalemkerian GP, Luo Y, Ebiana V, Pietanza MC, Kim HR; KEYNOTE-604 Investigators. Pembrolizumab or Placebo Plus Etoposide and Platinum as First-Line Therapy for Extensive-Stage Small-Cell Lung Cancer: Randomized, Double-Blind, Phase III KEYNOTE-604 Study. J Clin Oncol. 2020 Jul 20;38(21):2369-2379. Epub 2020 May 29. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors EuroPMC NCT03066778
##PRO analysis: Kim HR, Awad MM, Navarro A, Gottfried M, Peters S, Csőszi T, Cheema PK, Rodriguez-Abreu D, Wollner M, Yang JC, Mazieres J, Orlandi FJ, Luft A, Gümüş M, Kato T, Kalemkerian GP, Luo Y, Santorelli ML, Pietanza MC, Rudin CM. Patient-Reported Health-Related Quality of Life in KEYNOTE-604: Pembrolizumab or Placebo Added to Etoposide and Platinum as First-Line Therapy for Extensive-Stage SCLC. JTO Clin Res Rep. 2023 Sep 9;4(11):100572. link to original article link to PMC article EuroPMC
#RATIONALE-312: Cheng Y, Fan Y, Zhao Y, Huang D, Li X, Zhang P, Kang M, Yang N, Zhong D, Wang Z, Yu Y, Zhang Y, Zhao J, Qin T, Chen C, Leaw S, Zheng W, Song Y; RATIONALE-312 Study Group. Tislelizumab Plus Platinum and Etoposide Versus Placebo Plus Platinum and Etoposide as First-Line Treatment for Extensive-Stage SCLC (RATIONALE-312): A Multicenter, Double-Blind, Placebo-Controlled, Randomized, Phase 3 Clinical Trial. J Thorac Oncol. 2024 Jul;19(7):1073-1085. Epub 2024 Mar 7. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT04005716
#EXTENTORCH: Cheng Y, Zhang W, Wu L, Zhou C, Wang D, Xia B, Bi M, Fu X, Li C, Lv D, Zhao Y, Chen G, Yi T, Huang J, Li M, Yang R, Huang X, Wang Y, Zhang M, Pan Y, Sun Y, Hu S, Zhang X, Zhou M, Fang J, Jin F, Liu Y, Li Y, Zhang Z, Hu J, Liu L, Wang R, Li Y, Gu K, Ding C, Fan Q, Zhang G, Chen Y, Jiang L, Zheng WE, Chen S, Huang C, Han Z, Yang H, Wang J, Wang B, Wu H, Bao Y, Li M, Luo X, Gu S, Yu W, Xu K, Zhang S, Yu J. Toripalimab Plus Chemotherapy as a First-Line Therapy for Extensive-Stage Small Cell Lung Cancer: The Phase 3 EXTENTORCH Randomized Clinical Trial. JAMA Oncol. 2025 Jan 1;11(1):16-25. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article EuroPMC NCT04012606
==Cisplatin & Etoposide (EP) & Bevacizumab==
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Spigel et al. 2011 (SALUTE)	2007-2008 	Randomized Phase 2 (E-esc)	1a. CE1b. EP	Seems to have longer PFS (primary endpoint)Median PFS: 5.5 vs 4.4 mo(HR 0.53, 95% CI 0.32-0.86)
====Chemotherapy====
*Cisplatin (Platinol) 75 mg/m2 IV once on day 1
*Etoposide (Vepesid) 100 mg/m2 IV once per day on days 1 to 3
====Targeted therapy====
*Bevacizumab (Avastin) 15 mg/kg IV once on day 1
21-day cycle for 4 cycles
====Subsequent treatment====
*Bevacizumab maintenance
===References===
# SALUTE: Spigel DR, Townley PM, Waterhouse DM, Fang L, Adiguzel I, Huang JE, Karlin DA, Faoro L, Scappaticci FA, Socinski MA. Randomized phase II study of bevacizumab in combination with chemotherapy in previously untreated extensive-stage small-cell lung cancer: results from the SALUTE trial. J Clin Oncol. 2011 Jun 1;29(16):2215-22. Epub 2011 Apr 18. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT00403403
==Cisplatin & Etoposide (EP) & Durvalumab==
===Regimen===
Study 	Dates of enrollment 	Evidence 	Comparator 	Comparative Efficacy
Paz-Ares et al. 2019 (CASPIAN)	2017-03-27 to 2018-05-29	Phase 3 (E-RT-esc)	1a. CE1b. EP	Longer OS1 (primary endpoint)Median OS: 12.9 vs 10.5 mo(HR 0.75, 95% CI 0.62-0.91)
1Reported efficacy is based on the 2021 update.
====Chemotherapy====
*Cisplatin (Platinol) as follows:
**Cycles 1 to 4: 75 to 80 mg/m2 IV once on day 1
*Etoposide (Vepesid) as follows:
**Cycles 1 to 4: 80 to 100 mg/m2 IV once per day on days 1 to 3
====Immunotherapy====
*Durvalumab (Imfinzi) as follows:
**Cycles 1 to 4: 1500 mg IV once on day 1
**Cycle 5 onwards: 1500 mg IV once on day 1
21-day cycle for 4 cycles, then 28-day cycles
===References===
# CASPIAN: Paz-Ares L, Dvorkin M, Chen Y, Reinmuth N, Hotta K, Trukhin D, Statsenko G, Hochmair MJ, Özgüroğlu M, Ji JH, Voitko O, Poltoratskiy A, Ponce S, Verderame F, Havel L, Bondarenko I, Kazarnowicz A, Losonczy G, Conev NV, Armstrong J, Byrne N, Shire N, Jiang H, Goldman JW; CASPIAN investigators. Durvalumab plus platinum-etoposide versus platinum-etoposide in first-line treatment of extensive-stage small-cell lung cancer (CASPIAN): a randomised, controlled, open-label, phase 3 trial. Lancet. 2019 Nov 23;394(10212):1929-1939. Epub 2019 Oct 4. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT03043872
##PRO analysis: Goldman JW, Garassino MC, Chen Y, Özgüroğlu M, Dvorkin M, Trukhin D, Statsenko G, Hotta K, Ji JH, Hochmair MJ, Voitko O, Havel L, Poltoratskiy A, Losonczy G, Reinmuth N, Patel N, Laud PJ, Shire N, Jiang H, Paz-Ares L. Patient-reported outcomes with first-line durvalumab plus platinum-etoposide versus platinum-etoposide in extensive-stage small-cell lung cancer (CASPIAN): a randomized, controlled, open-label, phase III study. Lung Cancer. 2020 Nov;149:46-52. Epub 2020 Sep 10. link to original article EuroPMC
##Update: Goldman JW, Dvorkin M, Chen Y, Reinmuth N, Hotta K, Trukhin D, Statsenko G, Hochmair MJ, Özgüroğlu M, Ji JH, Garassino MC, Voitko O, Poltoratskiy A, Ponce S, Verderame F, Havel L, Bondarenko I, Każarnowicz A, Losonczy G, Conev NV, Armstrong J, Byrne N, Thiyagarajah P, Jiang H, Paz-Ares L; CASPIAN investigators. Durvalumab, with or without tremelimumab, plus platinum-etoposide versus platinum-etoposide alone in first-line treatment of extensive-stage small-cell lung cancer (CASPIAN): updated results from a randomised, controlled, open-label, phase 3 trial. Lancet Oncol. 2021 Jan;22(1):51-65. Epub 2020 Dec 4. link to original article EuroPMC
==Cisplatin & Etoposide (EP) & Tislelizumab==
===Regimen===
Study 	Dates of enrollment 	Evidence 	Comparator 	Comparative Efficacy
Cheng et al. 2024 (RATIONALE-312)	2019-07-22 to 2021-04-21	Phase 3 (E-esc)	1a. CE1b. EP	Longer OS (primary endpoint)Median OS: 15.5 vs 13.5 mo(HR 0.75, 95% CI 0.61-0.93)
====Chemotherapy====
*Cisplatin (Platinol) as follows:
**Cycles 1 to 4: 75 mg/m2 IV once on day 1
*Etoposide (Vepesid) as follows:
**Cycles 1 to 4: 100 mg/m2 IV once per day on days 1 to 3
====Immunotherapy====
*Tislelizumab (Baizean) 200 mg IV once on day 1
21-day cycles
===References===
#RATIONALE-312: Cheng Y, Fan Y, Zhao Y, Huang D, Li X, Zhang P, Kang M, Yang N, Zhong D, Wang Z, Yu Y, Zhang Y, Zhao J, Qin T, Chen C, Leaw S, Zheng W, Song Y; RATIONALE-312 Study Group. Tislelizumab Plus Platinum and Etoposide Versus Placebo Plus Platinum and Etoposide as First-Line Treatment for Extensive-Stage SCLC (RATIONALE-312): A Multicenter, Double-Blind, Placebo-Controlled, Randomized, Phase 3 Clinical Trial. J Thorac Oncol. 2024 Jul;19(7):1073-1085. Epub 2024 Mar 7. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT04005716
==Cisplatin & Etoposide (EP) & Toripalimab==
===Regimen===
Study 	Dates of enrollment 	Evidence 	Comparator	Comparative Efficacy
Cheng et al. 2024 (EXTENTORCH)	2019-09-26 to 2021-05-20	Phase 3 (E-esc)	EP 	Seems to have longer OS (co-primary endpoint)Median OS: 14.6 vs 13.3 mo(HR 0.80, 95% CI 0.65-0.98)Longer PFS (co-primary endpoint)Median PFS: 5.8 vs 5.6 mo(HR 0.67, 95% CI 0.54-0.82)
====Chemotherapy====
*Cisplatin (Platinol) as follows:
**Cycles 1 to 4 up to 6: 75 mg/m2 IV once on day 1
*Etoposide (Vepesid) as follows:
**Cycles 1 to 4 up to 6: 100 mg/m2 IV once per day on days 1 to 3
====Immunotherapy====
*Toripalimab (Loqtorzi) 240 mg IV once on day 1
21-day cycle for up to 35 cycles (2 years)
===References===
#EXTENTORCH: Cheng Y, Zhang W, Wu L, Zhou C, Wang D, Xia B, Bi M, Fu X, Li C, Lv D, Zhao Y, Chen G, Yi T, Huang J, Li M, Yang R, Huang X, Wang Y, Zhang M, Pan Y, Sun Y, Hu S, Zhang X, Zhou M, Fang J, Jin F, Liu Y, Li Y, Zhang Z, Hu J, Liu L, Wang R, Li Y, Gu K, Ding C, Fan Q, Zhang G, Chen Y, Jiang L, Zheng WE, Chen S, Huang C, Han Z, Yang H, Wang J, Wang B, Wu H, Bao Y, Li M, Luo X, Gu S, Yu W, Xu K, Zhang S, Yu J. Toripalimab Plus Chemotherapy as a First-Line Therapy for Extensive-Stage Small Cell Lung Cancer: The Phase 3 EXTENTORCH Randomized Clinical Trial. JAMA Oncol. 2025 Jan 1;11(1):16-25. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article EuroPMC NCT04012606
==Cisplatin & Irinotecan (IC)==
IP: Irinotecan, Platinol (Cisplatin)
===Regimen variant #1, 30/65===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Hanna et al. 2006	2000-2003 	Phase 3 (E-switch-ic)	Cisplatin & Etoposide	Did not meet primary endpoint of OS
====Chemotherapy====
*Cisplatin (Platinol) 30 mg/m2 IV once per day on days 1 & 8 
*Irinotecan (Camptosar) 65 mg/m2 IV once per day on days 1 & 8
====Supportive therapy====
*G-CSF used according to 1999 American Society of Clinical Oncology guidelines
*"Erythropoietin was allowed at the discretion of the treating physician."
21-day cycle for 4 cycles; additional cycles could be given at physician discretion
===Regimen variant #2, 60/60===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Noda et al. 2002 (JCOG 9511) 	1995-1998 	Phase 3 (E-switch-ic)	EP 	Longer OS (primary endpoint)Median OS: 12.8 vs 9.4 mo(HR 0.60, 95% CI 0.43-0.83)
Lara et al. 2009 (SWOG S0124) 	2002-2007 	Phase 3 (E-switch-ic)	EP 	Did not meet primary endpoint of OS
Satouchi et al. 2014 (JCOG 0509)	2007-2010 	Phase 3 (C) 	Amrubicin & Cisplatin	Longer OS
====Chemotherapy====
*Cisplatin (Platinol) 60 mg/m2 IV once on day 1
*Irinotecan (Camptosar) 60 mg/m2 IV once per day on days 1, 8, 15
====Supportive therapy====
*"Hydration and administration of antiemetic drugs."
28-day cycle for 4 cycles
===Regimen variant #3, 80/65===
Study 	Dates of enrollment	Evidence 	Comparator	Comparative Efficacy
Zatloukal et al. 2010	2003-2007 	Phase 3 (E-switch-ic)	EP 	Non-inferior OS (primary endpoint)Median OS: 10.2 vs 9.7 mo(HR 0.81, 95% CI 0.65-1.01)
Note: this dosing was the result of a mid-protocol amendment.
====Chemotherapy====
*Cisplatin (Platinol) 80 mg/m2 IV once on day 1
*Irinotecan (Camptosar) 65 mg/m2 IV once per day on days 1 & 8
21-day cycle for 6 cycles
===References===
# JCOG 9511: Noda K, Nishiwaki Y, Kawahara M, Negoro S, Sugiura T, Yokoyama A, Fukuoka M, Mori K, Watanabe K, Tamura T, Yamamoto S, Saijo N; JCOG. Irinotecan plus cisplatin compared with etoposide plus cisplatin for extensive small-cell lung cancer. N Engl J Med. 2002 Jan 10;346(2):85-91. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
# Hanna N, Bunn PA Jr, Langer C, Einhorn L, Guthrie T Jr, Beck T, Ansari R, Ellis P, Byrne M, Morrison M, Hariharan S, Wang B, Sandler A. Randomized phase III trial comparing irinotecan/cisplatin with etoposide/cisplatin in patients with previously untreated extensive-stage disease small-cell lung cancer. J Clin Oncol. 2006 May 1;24(13):2038-43. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
# SWOG S0124: Lara PN Jr, Natale R, Crowley J, Lenz HJ, Redman MW, Carleton JE, Jett J, Langer CJ, Kuebler JP, Dakhil SR, Chansky K, Gandara DR. Phase III trial of irinotecan/cisplatin compared with etoposide/cisplatin in extensive-stage small-cell lung cancer: clinical and pharmacogenomic results from SWOG S0124. J Clin Oncol. 2009 May 20;27(15):2530-5. Epub 2009 Apr 6. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors EuroPMC NCT00045162
# Zatloukal P, Cardenal F, Szczesna A, Gorbunova V, Moiseyenko V, Zhang X, Cisar L, Soria JC, Domine M, Thomas M. A multicenter international randomized phase III study comparing cisplatin in combination with irinotecan or etoposide in previously untreated small-cell lung cancer patients with extensive disease. Ann Oncol. 2010 Sep;21(9):1810-6. Epub 2010 Mar 15. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT00143455
# JCOG 0509: Satouchi M, Kotani Y, Shibata T, Ando M, Nakagawa K, Yamamoto N, Ichinose Y, Ohe Y, Nishio M, Hida T, Takeda K, Kimura T, Minato K, Yokoyama A, Atagi S, Fukuda H, Tamura T, Saijo N. Phase III study comparing amrubicin plus cisplatin with irinotecan plus cisplatin in the treatment of extensive-disease small-cell lung cancer: JCOG 0509. J Clin Oncol. 2014 Apr 20;32(12):1262-8. Epub 2014 Mar 17. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC UMIN000000720
==Docetaxel monotherapy==
===Regimen===
Study 	Dates of enrollment 	Evidence
Hesketh et al. 1999	Not reported in abstract	Phase 2
Note: The full manuscript was not available for review.
====Chemotherapy====
*Docetaxel (Taxotere) 100 mg/m2 IV over 60 minutes once on day 1
21-day cycles
===References===
# Hesketh PJ, Crowley JJ, Burris HA 3rd, Williamson SK, Balcerzak SP, Peereboom D, Goodwin JW, Gross HM, Moore DF Jr, Livingston RB, Gandara DR; SWOG. Evaluation of docetaxel in previously untreated extensive-stage small cell lung cancer: a Southwest Oncology Group phase II trial. Cancer J Sci Am. 1999 Jul-Aug;5(4):237-41. dosing details in abstract have been reviewed by our editors EuroPMC
==EP-Topotecan==
EP-Topotecan: Etoposide and Platinol (Cisplatin), followed by Topotecan
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Ignatiadis et al. 2005	2000-2003 	Phase 3 (C)	EP/Topotecan	Did not meet primary endpoint of OS
====Chemotherapy, EP portion (cycles 1 to 4)====
*Cisplatin (Platinol) 75 mg/m2 IV once on day 1
*Etoposide (Vepesid) 100 mg/m2 IV once per day on days 1 to 3
====Chemotherapy, Topotecan portion (cycles 5 to 8)====
*Topotecan (Hycamtin) 1.5 mg/m2 IV once per day on days 1 to 5
21-day cycle for 8 cycles
===References===
# Ignatiadis M, Mavroudis D, Veslemes M, Boukovinas J, Syrigos K, Agelidou M, Agelidou A, Gerogianni A, Pavlakou G, Tselepatiotis E, Nikolakopoulos J, Georgoulias V; Hellenic Oncology Research Group. Sequential versus alternating administration of cisplatin/etoposide and topotecan as first-line treatment in extensive-stage small-cell lung cancer: preliminary results of a Phase III Trial of the Hellenic Oncology Research Group. Clin Lung Cancer. 2005 Nov;7(3):183-9. link to original article dosing details in abstract have been reviewed by our editors EuroPMC
==Ifosfamide monotherapy==
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy 	Comparative Toxicity
Ettinger et al. 2002 (ECOG E1588)	1988-1990 	Phase 3 (E-switch-ic)	1. CAV 	Did not meet primary endpoint of OS	Less toxic
Ettinger et al. 2002 (ECOG E1588)	1988-1990 	Phase 3 (E-switch-ic)	2. Teniposide	Did not meet primary endpoint of OS	Not reported
====Chemotherapy====
*Ifosfamide (Ifex) 1500 mg/m2 IV once per day on days 1 to 5
====Supportive therapy====
*Mesna (Mesnex) 300 mg/m2 IV three times per day on days 1 to 5, given 0, 4, and 8 hours after each dose of ifosfamide (total dose per cycle: 4500 mg/m2)
21-day cycle for 4 to 6 cycles 
====Subsequent treatment====
*ECOG E1588, patients with CR: Ifosfamide continuation x 2 cycles, then prophylactic whole-brain irradiation if still in CR
*ECOG E1588, patients with PR: Ifosfamide continuation until progression of disease, then salvage EP
===References===
# ECOG E1588: Ettinger DS, Finkelstein DM, Ritch PS, Lincoln ST, Blum RH; ECOG. Study of either ifosfamide or teniposide compared to a standard chemotherapy for extensive disease small cell lung cancer: an Eastern Cooperative Oncology Group randomized study (E1588). Lung Cancer. 2002 Sep;37(3):311-8. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
==IVE==
IVE: Ifosfamide, VP-16 (Etoposide), Epirubicin
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator	Comparative Efficacy
Berghmans et al. 2017 (ELCWP 01994)	2000-2013 	Phase 3 (C)	EP 	Did not meet primary endpoint of OS
Note: This combination is based on a commonly used backbone in Europe. To our knowledge, this regimen was not tested as an experimental arm in an RCT prior to becoming a standard comparator arm.
====Chemotherapy====
*Ifosfamide (Ifex) 1500 mg/m2 IV once per day on days 1 to 3
*Etoposide (Vepesid) 100 mg/m2 IV once per day on days 1 to 3
*Epirubicin (Ellence) 60 mg/m2 IV once on day 1
====Supportive therapy====
*Mesna (Mesnex) 300 mg/m2 IV once on day 1, given just before ifosfamide, then 300 mg/m2 IV once every 4 hours for 72 hours (total dose per cycle: 5700 mg/m2)
21-day cycles
===References===
#ELCWP 01994: Berghmans T, Scherpereel A, Meert AP, Giner V, Lecomte J, Lafitte JJ, Leclercq N, Paesmans M, Sculier JP; European Lung Cancer Working Party (ELCWP). A Phase III Randomized Study Comparing a Chemotherapy with Cisplatin and Etoposide to a Etoposide Regimen without Cisplatin for Patients with Extensive Small-Cell Lung Cancer. Front Oncol. 2017 Sep 19;7:217. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors EuroPMC NCT00658580
==Teniposide monotherapy==
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy 	Comparative Toxicity
Ettinger et al. 2002 (ECOG E1588)	1988-1990 	Phase 3 (E-switch-ic)	1. CAV 	Did not meet primary endpoint of OS	Less toxic
Ettinger et al. 2002 (ECOG E1588)	1988-1990 	Phase 3 (E-switch-ic)	2. Ifosfamide	Did not meet primary endpoint of OS	Not reported
====Chemotherapy====
*Teniposide (Vumon) 60 mg/m2 IV once per day on days 1 to 5
21-day cycle for 4 to 6 cycles 
====Subsequent treatment====
*ECOG E1588, patients with CR after 4 to 6 cycles: Teniposide continuation x 2 cycles
*ECOG E1588, patients with CR after 6 to 8 cycles: prophylactic whole-brain irradiation
*ECOG E1588, patients with PR: Teniposide continuation until progression of disease, then salvage EP
===References===
# ECOG E1588: Ettinger DS, Finkelstein DM, Ritch PS, Lincoln ST, Blum RH; ECOG. Study of either ifosfamide or teniposide compared to a standard chemotherapy for extensive disease small cell lung cancer: an Eastern Cooperative Oncology Group randomized study (E1588). Lung Cancer. 2002 Sep;37(3):311-8. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
=Extensive stage, consolidation after first-line therapy=
==Whole brain irradiation==
PCI: Prophylactic Cranial Irradiation
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Ettinger et al. 2002 (ECOG E1588)	1988-1990 	Non-randomized part of phase 3 RCT	 	
Slotman et al. 2007 (EORTC 22993)	2001-2006 	Phase 3 (E-esc) 	Observation	Longer OS (secondary endpoint)Median OS: 6.7 vs 5.4 mo(HR 0.68, 95% CI 0.52-0.88)
====Preceding treatment====
*ECOG E1588: CAV versus Ifosfamide versus Teniposide
*EORTC 22993: Chemotherapy x 4 to 6 cycles (regimen not specified)
====Radiotherapy====
*Whole brain irradiation by one of the following: 2000 cGy in 5 or 8 fractions, 2400 cGy in 12 fractions, 2500 cGy in 10 fractions, or 3000 cGy in 10 or 12 fractions
1- to 3-week course
===References===
# Meta-analysis: Aupérin A, Arriagada R, Pignon JP, Le Péchoux C, Gregor A, Stephens RJ, Kristjansen PE, Johnson BE, Ueoka H, Wagner H, Aisner J; Prophylactic Cranial Irradiation Overview Collaborative Group. Prophylactic cranial irradiation for patients with small-cell lung cancer in complete remission. N Engl J Med. 1999 Aug 12;341(7):476-84. link to original article EuroPMC
# ECOG E1588: Ettinger DS, Finkelstein DM, Ritch PS, Lincoln ST, Blum RH; ECOG. Study of either ifosfamide or teniposide compared to a standard chemotherapy for extensive disease small cell lung cancer: an Eastern Cooperative Oncology Group randomized study (E1588). Lung Cancer. 2002 Sep;37(3):311-8. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
# EORTC 22993: Slotman B, Faivre-Finn C, Kramer G, Rankin E, Snee M, Hatton M, Postmus P, Collette L, Musat E, Senan S; EORTC Radiation Oncology Group; EORTC Lung Cancer Group. Prophylactic cranial irradiation in extensive small-cell lung cancer. N Engl J Med. 2007 Aug 16;357(7):664-72. link to original article dosing details in abstract have been reviewed by our editors EuroPMC NCT00016211
=Extensive stage, maintenance after first-line therapy=
==Bevacizumab monotherapy==
===Regimen===
Study 	Dates of enrollment	Evidence
Spigel et al. 2011 (SALUTE)	2007-2008 	Non-randomized part of phase 2 RCT
====Preceding treatment====
*CE & Bevacizumab induction x 4 or EP & Bevacizumab induction x 4
====Targeted therapy====
*Bevacizumab (Avastin) 15 mg/kg IV once on day 1
21-day cycles
===References===
# Spigel DR, Townley PM, Waterhouse DM, Fang L, Adiguzel I, Huang JE, Karlin DA, Faoro L, Scappaticci FA, Socinski MA. Randomized phase II study of bevacizumab in combination with chemotherapy in previously untreated extensive-stage small-cell lung cancer: results from the SALUTE trial. J Clin Oncol. 2011 Jun 1;29(16):2215-22. Epub 2011 Apr 18. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT00403403
==Ipilimumab monotherapy==
===Regimen===
Study 	Dates of enrollment	Evidence
Reck et al. 2012 (CA184-041SCLC)	2008-2009 	Non-randomized part of phase 2 RCT
====Preceding treatment====
*Carboplatin, Paclitaxel, Ipilimumab induction
====Immunotherapy====
*Ipilimumab (Yervoy) 10 mg/kg IV once on day 1
12-week cycles 
===References===
# CA184-041SCLC: Reck M, Bondarenko I, Luft A, Serwatowski P, Barlesi F, Chacko R, Sebastian M, Lu H, Cuillerot JM, Lynch TJ. Ipilimumab in combination with paclitaxel and carboplatin as first-line therapy in extensive-disease-small-cell lung cancer: results from a randomized, double-blind, multicenter phase 2 trial. Ann Oncol. 2013 Jan;24(1):75-83. Epub 2012 Aug 2. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT00527735
==Sunitinib monotherapy==
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Ready et al. 2015 (CALGB 30504)	2007-2011 	Randomized Phase 2 (E-esc)	Observation	Seems to have longer PFS (primary endpoint)Median PFS: 3.7 vs 2.1 mo(HR 0.62, 95% CI 0.38-0.98)
====Preceding treatment====
*Carboplatin & Etoposide or Cisplatin & Etoposide for 4 to 6 cycles
====Targeted therapy====
*Sunitinib (Sutent) as follows:
**Cycle 1: 150 mg PO once on day 1, then 37.5 mg PO once per day on days 2 to 28
**Cycle 2 onwards: 37.5 mg PO once per day on days 1 to 28
28-day cycles
===References===
# CALGB 30504: Ready NE, Pang HH, Gu L, Otterson GA, Thomas SP, Miller AA, Baggstrom M, Masters GA, Graziano SL, Crawford J, Bogart J, Vokes EE. Chemotherapy with or without maintenance sunitinib for untreated extensive-stage small-cell lung cancer: A randomized, double-blind, placebo-controlled phase II study-CALGB 30504 (Alliance). J Clin Oncol. 2015 May 20;33(15):1660-5. Epub 2015 Mar 2. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors EuroPMC NCT00453154
=Relapsed or refractory disease, second-line=
==Amrubicin monotherapy==
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator	Comparative Efficacy
von Pawel et al. 2014 (ACT-1) 	2007-2010 	Phase 3 (E-switch-ic)	Topotecan 	Did not meet primary endpoint of OSMedian OS: 7.5 vs 7.8 mo(HR 0.88, 95% CI 0.73-1.06)
Spigel et al. 2021 (CheckMate 331)	2015-2017 	Phase 3 (C) 	Nivolumab 	Might have shorter OSMedian OS: 8.4 vs 7.5 mo(HR 1.16, 95% CI 0.96-1.39)
====Chemotherapy====
*Amrubicin (Calsed) 40 mg/m2 IV over 5 minutes once per day on days 1 to 3
====Supportive therapy====
*"Prophylactic antibiotics were recommended for patients at high risk of infectious complications."
21-day cycle for at least 6 cycles
===References===
# ACT-1: von Pawel J, Jotte R, Spigel DR, O'Brien ME, Socinski MA, Mezger J, Steins M, Bosquée L, Bubis J, Nackaerts K, Trigo JM, Clingan P, Schütte W, Lorigan P, Reck M, Domine M, Shepherd FA, Li S, Renschler MF. Randomized phase III trial of amrubicin versus topotecan as second-line treatment for patients with small-cell lung cancer. J Clin Oncol. 2014 Dec 10;32(35):4012-9. Epub 2014 Nov 10. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT00547651
# CheckMate 331: Spigel DR, Vicente D, Ciuleanu TE, Gettinger S, Peters S, Horn L, Audigier-Valette C, Pardo Aranda N, Juan-Vidal O, Cheng Y, Zhang H, Shi M, Luft A, Wolf J, Antonia S, Nakagawa K, Fairchild J, Baudelet C, Pandya D, Doshi P, Chang H, Reck M. Second-line nivolumab in relapsed small-cell lung cancer: CheckMate 331. Ann Oncol. 2021 May;32(5):631-641. Epub 2021 Feb 1. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT02481830
==Carboplatin & Etoposide (CE)==
EC: Etoposide & Carboplatin
EP: Etoposide & Paraplatin (Carboplatin)
CE: Carboplatin & Etoposide
Ca/E: Carboplatin & Etoposide
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator	Comparative Efficacy
Baize et al. 2020 (GFPC 01-2013)	2013-2018 	Phase 3 (E-switch-ic)	Topotecan 	Longer PFS (primary endpoint)Median PFS: 4.7 vs 2.7 mo(HR 0.57, 90% CI 0.41-0.73)
====Chemotherapy====
*Carboplatin (Paraplatin) AUC 5 IV once on day 1
*Etoposide (Vepesid) 100 mg/m2 IV once per day on days 1 to 3
21-day cycle for 6 cycles
===References===
#GFPC 01-2013: Baize N, Monnet I, Greillier L, Geier M, Lena H, Janicot H, Vergnenegre A, Crequit J, Lamy R, Auliac JB, Letreut J, Le Caer H, Gervais R, Dansin E, Madroszyk A, Renault PA, Le Garff G, Falchero L, Berard H, Schott R, Saulnier P, Chouaid C; Groupe Français de Pneumo-Cancérologie. Carboplatin plus etoposide versus topotecan as second-line treatment for patients with sensitive relapsed small-cell lung cancer: an open-label, multicentre, randomised, phase 3 trial. Lancet Oncol. 2020 Sep;21(9):1224-1233. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT02738346
==Cisplatin, Etoposide, Irinotecan==
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator	Comparative Efficacy
Goto et al. 2016 (JCOG0605)	2007-2012 	Phase 3 (E-esc)	Topotecan 	Longer OS (primary endpoint)Median OS: 18.2 vs 12.5 mo(HR 0.67, 90% CI 0.51-0.88)
====Chemotherapy====
*Cisplatin (Platinol) 25 mg/m2 IV over 60 minutes once per day on days 1 & 8
*Etoposide (Vepesid) 60 mg/m2 IV over 60 minutes once per day on days 1 to 3
*Irinotecan (Camptosar) 90 mg/m2 IV over 90 minutes once on day 8
====Supportive therapy====
*G-CSF, started on cycle 1 day 9: (dose not specified) SC once per day, continued throughout except for days of chemotherapy
14-day cycle for 5 cycles
===References===
# JCOG0605: Goto K, Ohe Y, Shibata T, Seto T, Takahashi T, Nakagawa K, Tanaka H, Takeda K, Nishio M, Mori K, Satouchi M, Hida T, Yoshimura N, Kozuki T, Imamura F, Kiura K, Okamoto H, Sawa T, Tamura T; JCOG. Combined chemotherapy with cisplatin, etoposide, and irinotecan versus topotecan alone as second-line treatment for patients with sensitive relapsed small-cell lung cancer (JCOG0605): a multicentre, open-label, randomised phase 3 trial. Lancet Oncol. 2016 Aug;17(8):1147-57. Epub 2016 Jun 14. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC UMIN000000828
==Lurbinectedin monotherapy==
===Regimen===
Study 	Dates of enrollment	Evidence 	Efficacy
Trigo et al. 2020 (PM1183-B-005-14)	2015-2019 	Phase 2 (RT)	ORR: 35.2% (95% CI, 26.2-45.2%)
====Chemotherapy====
*Lurbinectedin (Zepzelca) 3.2 mg/m2 IV over 60 minutes once on day 1
====Supportive therapy====
*"All patients received antiemetic prophylaxis."
21-day cycles 
===References===
# PM1183-B-005-14: Trigo J, Subbiah V, Besse B, Moreno V, López R, Sala MA, Peters S, Ponce S, Fernández C, Alfaro V, Gómez J, Kahatt C, Zeaiter A, Zaman K, Boni V, Arrondeau J, Martínez M, Delord JP, Awada A, Kristeleit R, Olmedo ME, Wannesson L, Valdivia J, Rubio MJ, Anton A, Sarantopoulos J, Chawla SP, Mosquera-Martinez J, D'Arcangelo M, Santoro A, Villalobos VM, Sands J, Paz-Ares L. Lurbinectedin as second-line treatment for patients with small-cell lung cancer: a single-arm, open-label, phase 2 basket trial. Lancet Oncol. 2020 May;21(5):645-654. Epub 2020 Mar 27. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT02454972
=Relapsed or refractory disease, subsequent lines=
This section includes studies that do not specify an exact line or have yet to be categorized.
==Bendamustine monotherapy==
===Regimen===
Study 	Dates of enrollment	Evidence	Efficacy
Lammers et al. 2014 (VICC THO 0920)	2009-2012 	Phase 2 	ORR: 33% (95% CI, 14-52%)
====Chemotherapy====
*Bendamustine 120 mg/m2 IV once per day on days 1 & 2
21-day cycle for up to 6 cycles
===References===
# VICC THO 0920: Lammers PE, Shyr Y, Li CI, Hutchison AS, Sandler A, Carbone DP, Johnson DH, Keedy VL, Horn L. Phase II study of bendamustine in relapsed chemotherapy sensitive or resistant small-cell lung cancer. J Thorac Oncol. 2014 Apr;9(4):559-62. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors EuroPMC NCT00984542
==CAV==
CAV: Cyclophosphamide, Adriamycin (Doxorubicin), Vincristine
===Regimen variant #1, no capping===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Aix et al. 2022 (ATLANTIS)	2016-2018 	Phase 3 (C)	Doxorubicin & Lurbinectedin	Did not meet primary endpoint of OSMedian OS: 7.6 vs 8.6 mo(HR 1.03, 95% CI 0.87-1.22)
====Chemotherapy====
*Cyclophosphamide (Cytoxan) 1000 mg/m2 IV once on day 1
*Doxorubicin (Adriamycin) 45 mg/m2 IV once on day 1
*Vincristine (Oncovin) 2 mg IV once on day 1
21-day cycle for up to 10 cycles
===Regimen variant #2, capped===
Study 	Dates of enrollment	Evidence 	Comparator	Comparative Efficacy
von Pawel et al. 1999	Not reported 	Phase 3 (C)	Topotecan 	Did not meet co-primary endpoints of ORR/DOR
Note: von Pawel et al. 1999 does not clearly state the duration of each cycle, but 21 days is used in other CAV regimens, and there was no information in the paper that contradicted this.
====Chemotherapy====
*Cyclophosphamide (Cytoxan) 1000 mg/m2 (maximum dose of 2000 mg) (route not specified) once on day 1
*Doxorubicin (Adriamycin) 45 mg/m2 (maximum dose of 100 mg) IV once on day 1
*Vincristine (Oncovin) 2 mg IV once on day 1
====Supportive therapy====
*G-CSF use per physician discretion
21-day cycle for up to 6 cycles beyond maximal response
Patients with stable disease after 4 cycles could have treatment discontinued at physician discretion.
===Regimen variant #3===
Study 	Dates of enrollment	Evidence
Ihde et al. 1994	1983-1991 	Non-randomized part of phase 3 RCT
Note: Ihde et al. 1994 did not specifically say that the three medications were all given on day 1, but this is assumed to be the case based on other CAV regimens.
====Preceding treatment====
*EP; standard-dose versus EP; high-dose, with progression
====Chemotherapy====
*Cyclophosphamide (Cytoxan) 1000 mg/m2 IV once on day 1
*Doxorubicin (Adriamycin) 45 mg/m2 IV once on day 1
*Vincristine (Oncovin) 1.4 mg/m2 (maximum dose of 2 mg) IV once on day 1
21-day cycle for 4 cycles
===References===
# Ihde DC, Mulshine JL, Kramer BS, Steinberg SM, Linnoila RI, Gazdar AF, Edison M, Phelps RM, Lesar M, Phares JC, Grayson J, Minna JD, Johnson BE. Prospective randomized comparison of high-dose and standard-dose etoposide and cisplatin chemotherapy in patients with extensive-stage small-cell lung cancer. J Clin Oncol. 1994 Oct;12(10):2022-34. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
# von Pawel J, Schiller JH, Shepherd FA, Fields SZ, Kleisbauer JP, Chrysson NG, Stewart DJ, Clark PI, Palmer MC, Depierre A, Carmichael J, Krebs JB, Ross G, Lane SR, Gralla R. Topotecan versus cyclophosphamide, doxorubicin, and vincristine for the treatment of recurrent small-cell lung cancer. J Clin Oncol. 1999 Feb;17(2):658-67. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
#ATLANTIS: Aix SP, Ciuleanu TE, Navarro A, Cousin S, Bonanno L, Smit EF, Chiappori A, Olmedo ME, Horvath I, Grohé C, Farago AF, López-Vilariño JA, Cullell-Young M, Nieto A, Vasco N, Gómez J, Kahatt C, Zeaiter A, Carcereny E, Roubec J, Syrigos K, Lo G, Barneto I, Pope A, Sánchez A, Kattan J, Zarogoulidis K, Waller CF, Bischoff H, Juan-Vidal O, Reinmuth N, Dómine M, Paz-Ares L. Combination lurbinectedin and doxorubicin versus physician's choice of chemotherapy in patients with relapsed small-cell lung cancer (ATLANTIS): a multicentre, randomised, open-label, phase 3 trial. Lancet Respir Med. 2023 Jan;11(1):74-86. Epub 2022 Oct 14. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT02566993
==Cisplatin & Etoposide (EP)==
EP: Etoposide, Platinol (Cisplatin)
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator	Comparative Efficacy
O'Bryan et al. 1990 (SWOG S8215) 	Not reported 	Phase 3 (E-switch-ic) 	BTOC 	Did not meet efficacy endpoints
Ettinger et al. 2002 (ECOG E1588)	1988-1990 	Non-randomized part of phase 3 RCT	 	
====Preceding treatment====
*ECOG E1588: CAV versus ifosfamide versus teniposide, with progression
====Chemotherapy====
*Cisplatin (Platinol) 60 mg/m2 IV once on day 1 
*Etoposide (Vepesid) 120 mg/m2 IV once per day on days 1 to 3
21-day cycles
===References===
# SWOG S8215: O'Bryan RM, Crowley JJ, Kim PN, Epstein RB, Neilan B, Coltman CA Jr, Stuckey WJ, Pazdur R. Comparison of etoposide and cisplatin with bis-chloro-ethylnitrosourea, thiotepa, vincristine, and cyclophosphamide for salvage treatment in small cell lung cancer: a Southwest Oncology Group Study. Cancer. 1990 Feb 15;65(4):856-60. link to original article EuroPMC
# ECOG E1588: Ettinger DS, Finkelstein DM, Ritch PS, Lincoln ST, Blum RH; ECOG. Study of either ifosfamide or teniposide compared to a standard chemotherapy for extensive disease small cell lung cancer: an Eastern Cooperative Oncology Group randomized study (E1588). Lung Cancer. 2002 Sep;37(3):311-8. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
==Docetaxel monotherapy==
===Regimen===
Study 	Dates of enrollment	Evidence
Smyth et al. 1994	Not reported 	Phase 2
====Chemotherapy====
*Docetaxel (Taxotere) 100 mg/m2 IV over 60 minutes once on day 1
21-day cycles
===References===
# Smyth JF, Smith IE, Sessa C, Schoffski P, Wanders J, Franklin H, Kaye SB; Early Clinical Trials Group of the EORTC. Activity of docetaxel (Taxotere) in small cell lung cancer. Eur J Cancer. 1994;30A(8):1058-60. link to original article dosing details in abstract have been reviewed by our editors EuroPMC
==Epirubicin & Ifosfamide==
EI: Epirubicin, Ifosfamide
===Regimen===
Study 	Dates of enrollment	Evidence
Jacot et al. 2012	1992-2010 	Phase 2
====Chemotherapy====
*Epirubicin (Ellence) 90 mg/m2 IV once on day 1
*Ifosfamide (Ifex) 3000 mg/m2 IV once per day on days 1 & 2
====Supportive therapy====
*Mesna (Mesnex) (dose/route/schedule not specified) on days 1 & 2
*G-CSF use per physician discretion
28-day cycle for up to 6 cycles
===References===
# Jacot W, Pujol JL, Chakra M, Molinier O, Bozonnat MC, Gervais R, Quantin X. Epirubicin and ifosfamide in relapsed or refractory small cell lung cancer patients. Lung Cancer. 2012 Feb;75(2):213-6. Epub 2011 Aug 9. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
==Etoposide monotherapy==
===Regimen===
Study 	Dates of enrollment 	Evidence
Einhorn et al. 1990	Not reported in abstract	Phase 2
Johnson et al. 1990	1988-07 to 1990-01 	Phase 2
Note: The full manuscript for Einhorn et al. 1990 was not available for review.
====Chemotherapy====
*Etoposide (Vepesid) 50 mg/m2 PO once per day on days 1 to 21, taken on an empty stomach
21-day cycles
===References===
# Einhorn LH, Pennington K, McClean J; Hoosier Oncology Group. Phase II trial of daily oral VP-16 in refractory small cell lung cancer: a Hoosier Oncology Group study. Semin Oncol. 1990 Feb;17(1 Suppl 2):32-5. Not available online; abstract contains protocol EuroPMC
# Johnson DH, Greco FA, Strupp J, Hande KR, Hainsworth JD. Prolonged administration of oral etoposide in patients with relapsed or refractory small-cell lung cancer: a phase II trial. J Clin Oncol. 1990 Oct;8(10):1613-7. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
==Gemcitabine monotherapy==
===Regimen variant #1, 5 cycles===
Study 	Dates of enrollment	Evidence
van der Lee et al. 2001	1997-02 to 1998-11 	Phase 2
====Chemotherapy====
*Gemcitabine (Gemzar) 1000 mg/m2 IV over 30 minutes once per day on days 1, 8, 15
28-day cycle for up to 5 cycles
===Regimen variant #2, indefinite===
Study 	Dates of enrollment 	Evidence
Masters et al. 2003 (ECOG E1597)	1997-12-05 to 1998-09-04	Phase 2
Note: dose escalation was carried out if patients had less than grade 2 toxicity with cycle 1.
====Chemotherapy====
*Gemcitabine (Gemzar) as follows:
**Cycle 1: 1000 mg/m2 IV over 30 minutes once per day on days 1, 8, 15
**Cycle 2 onwards: 1250 mg/m2 IV over 30 minutes once per day on days 1, 8, 15
28-day cycles
===References===
# van der Lee I, Smit EF, van Putten JW, Groen HJ, Schlösser NJ, Postmus PE, Schramel FM. Single-agent gemcitabine in patients with resistant small-cell lung cancer. Ann Oncol. 2001 Apr;12(4):557-61. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
# ECOG E1597: Masters GA, Declerck L, Blanke C, Sandler A, DeVore R, Miller K, Johnson D; ECOG. Phase II trial of gemcitabine in refractory or relapsed small-cell lung cancer: Eastern Cooperative Oncology Group Trial 1597. J Clin Oncol. 2003 Apr 15;21(8):1550-5. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
==Ifosfamide monotherapy==
===Regimen===
Study 	Dates of enrollment	Evidence
Cantwell et al. 1988	Not reported 	Phase 2
====Chemotherapy====
*Ifosfamide (Ifex) 5000 mg/m2 IV once on day 1
====Supportive therapy====
*Mesna (Mesnex) 5000 mg/m2 IV once on day 1
21-day cycles
===References===
# Cantwell BM, Bozzino JM, Corris P, Harris AL. The multidrug resistant phenotype in clinical practice; evaluation of cross resistance to ifosfamide and mesna after VP16-213, doxorubicin and vincristine (VPAV) for small cell lung cancer. Eur J Cancer Clin Oncol. 1988 Feb;24(2):123-9. link to original article dosing details in abstract have been reviewed by our editors EuroPMC
# Review: Marangolo M, Giovanis P. Ifosfamide in small cell lung cancer. Oncology. 2003;65 Suppl 2:46-9. Review. link to original article EuroPMC
==Ifosfamide & Paclitaxel==
PI: Paclitaxel, Ifosfamide
===Regimen===
Study 	Dates of enrollment	Evidence
Park et al. 2007a	2002-10 to 2006-03 	Phase 2
====Chemotherapy====
*Ifosfamide (Ifex) 2500 mg/m2 IV over 2 hours once per day on days 1 & 2
*Paclitaxel (Taxol) 175 mg/m2 IV over 3 hours once on day 1
====Supportive therapy====
*Mesna (Mesnex) 500 mg/m2 IV three times per day on days 1 & 2, given 15 minutes before, 4 hours after, and 8 hours after ifosfamide (total dose per cycle: 3000 mg/m2) 
21-day cycles
===References===
# Park S, Ahn MJ, Ahn JS, Lee J, Hong YS, Park BB, Lee SC, Hwang IG, Park JO, Lim H, Kang WK, Park K. Combination chemotherapy with paclitaxel and ifosfamide as the third-line regimen in patients with heavily pretreated small cell lung cancer. Lung Cancer. 2007 Oct;58(1):116-22. Epub 2007 Jul 12. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
==Irinotecan monotherapy==
===Regimen variant #1, weekly===
Study 	Dates of enrollment	Evidence
Masuda et al. 1992	Not reported 	Phase 2, fewer than 20 pts
====Chemotherapy====
*Irinotecan (Camptosar) 100 mg/m2 IV over 90 minutes once per day on days 1, 8, 15
====Supportive therapy====
*No routine prophylaxis against diarrhea, nausea, or vomiting used.
21-day cycles
===Regimen variant #2, q3wk===
Study 	Dates of enrollment 	Evidence 	Comparator 	Comparative Efficacy
Edelman et al. 2022 (DISTINCT)	2017 to not reported	Phase 3 (C)	1. Irinotecan & Dinutuximab	Did not meet primary endpoint of OSMedian OS: 7 vs 6.9 mo
Edelman et al. 2022 (DISTINCT)	2017 to not reported	Phase 3 (C)	2. Topotecan 	Not reported
====Chemotherapy====
*Irinotecan (Camptosar) 350 mg/m2 IV once on day 1
21-day cycles
===References===
# Masuda N, Fukuoka M, Kusunoki Y, Matsui K, Takifuji N, Kudoh S, Negoro S, Nishioka M, Nakagawa K, Takada M. CPT-11: a new derivative of camptothecin for the treatment of refractory or relapsed small-cell lung cancer. J Clin Oncol. 1992 Aug;10(8):1225-9. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
#DISTINCT: Edelman MJ, Dvorkin M, Laktionov K, Navarro A, Juan-Vidal O, Kozlov V, Golden G, Jordan O, Deng CQ, Bentsion D, Chouaid C, Dechev H, Dowlati A, Fernández Núñez N, Ivashchuk O, Kiladze I, Kortua T, Leighl N, Luft A, Makharadze T, Min Y, Quantin X; DISTINCT study investigators. Randomized phase 3 study of the anti-disialoganglioside antibody dinutuximab and irinotecan vs irinotecan or topotecan for second-line treatment of small cell lung cancer. Lung Cancer. 2022 Apr;166:135-142. Epub 2022 Mar 4. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT03098030
==Paclitaxel monotherapy==
===Regimen variant #1, every 3 weeks===
Study 	Dates of enrollment	Evidence
Smit et al. 1998	1994-12 to 1996-06 	Phase 2
====Chemotherapy====
*Paclitaxel (Taxol) 175 mg/m2 IV over 3 hours once on day 1
====Supportive therapy====
*Dexamethasone (Decadron) 8 mg PO given twice on day 1; 12 and 6 hours prior to paclitaxel
*Clemastine (Tavist) 2 mg IV push once on day 1; 30 minutes prior to paclitaxel
*One of the following H2 blockers:
**Cimetidine (Tagamet) 300 mg IV push once on day 1; 30 minutes prior to paclitaxel
**Ranitidine (Zantac) 50 mg IV push once on day 1; 30 minutes prior to paclitaxel
21-day cycle for up to 5 cycles
===Regimen variant #2, weekly paclitaxel===
Study 	Dates of enrollment	Evidence
Yamamoto et al. 2006	1999-12 to 2002-02 	Phase 2
====Chemotherapy====
*Paclitaxel (Taxol) 80 mg/m2 IV over 60 minutes once per day on days 1, 8, 15, 22, 29, 36
====Supportive therapy====
*Dexamethasone (Decadron) 20 mg IV once per day on days 1, 8, 15, 22, 29, 36; 30 minutes prior to paclitaxel
*Ranitidine (Zantac) 50 mg IV once per day on days 1, 8, 15, 22, 29, 36; 30 minutes prior to paclitaxel
*Diphenhydramine (Benadryl) 50 mg IV once per day on days 1, 8, 15, 22, 29, 36; 30 minutes prior to paclitaxel
*If ANC less than 1000/μL or WBC count less than 2 x 109/L, G-CSF (type not specified) 2 mcg/kg SC once per day, continued until WBC count more than or equal to 10 x 109/L, except on days that paclitaxel is given
8-week cycles
===References===
# Smit EF, Fokkema E, Biesma B, Groen HJ, Snoek W, Postmus PE. A phase II study of paclitaxel in heavily pretreated patients with small-cell lung cancer. Br J Cancer. 1998;77(2):347-51. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article EuroPMC
# Yamamoto N, Tsurutani J, Yoshimura N, Asai G, Moriyama A, Nakagawa K, Kudoh S, Takada M, Minato Y, Fukuoka M. Phase II study of weekly paclitaxel for relapsed and refractory small cell lung cancer. Anticancer Res. 2006 Jan-Feb;26(1B):777-81. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
==Tarlatamab monotherapy==
===Regimen===
Study 	Dates of enrollment	Evidence
Ahn et al. 2023 (DeLLphi-301)	2021-12 to 2023-05 	Phase 2 (RT)
====Immunotherapy====
*Tarlatamab (Imdelltra) as follows:
**Cycle 1: 1 mg IV over 60 minutes once on day 1, then 10 mg IV once on day 8
**Cycle 2 onwards: 10 mg IV once on day 1
14-day cycles
===References===
#DeLLphi-301: Ahn MJ, Cho BC, Felip E, Korantzis I, Ohashi K, Majem M, Juan-Vidal O, Handzhiev S, Izumi H, Lee JS, Dziadziuszko R, Wolf J, Blackhall F, Reck M, Bustamante Alvarez J, Hummel HD, Dingemans AC, Sands J, Akamatsu H, Owonikoko TK, Ramalingam SS, Borghaei H, Johnson ML, Huang S, Mukherjee S, Minocha M, Jiang T, Martinez P, Anderson ES, Paz-Ares L; DeLLphi-301 Investigators. Tarlatamab for Patients with Previously Treated Small-Cell Lung Cancer. N Engl J Med. 2023 Nov 30;389(22):2063-2075. Epub 2023 Oct 20. link to original article EuroPMC NCT05060016
==Temozolomide monotherapy==
===Regimen variant #1, 75 mg/m2/d, 21 out of 28 days===
Study 	Dates of enrollment	Evidence
Pietanza et al. 2012	2008-2010 	Phase 2
====Chemotherapy====
*Temozolomide (Temodar) 75 mg/m2 PO once per day on days 1 to 21 (no food within 2 hours before or 1 hour after temozolomide)
====Supportive therapy====
*Ondansetron (Zofran) 8 mg PO once per day on days 1 to 21, taken prior to temozolomide prn nausea
*Patients with at least grade 3 lymphopenia received prophylaxis for Pneumocystis carinii pneumonia (no specific medication/dose/schedule listed)
28-day cycles
===Regimen variant #2, 200 mg/m2/d, 5 out of 28 days===
Study 	Dates of enrollment	Evidence
Zauderer et al. 2014 (MSKCC 08-065)	Not reported 	Phase 2
====Chemotherapy====
*Temozolomide (Temodar) 200 mg/m2 PO once per day on days 1 to 5
====Supportive therapy====
*Ondansetron (Zofran) 8 mg PO once per day on days 1 to 5; 30 minutes prior to temozolomide
28-day cycles
===References===
# Pietanza MC, Kadota K, Huberman K, Sima CS, Fiore JJ, Sumner DK, Travis WD, Heguy A, Ginsberg MS, Holodny AI, Chan TA, Rizvi NA, Azzoli CG, Riely GJ, Kris MG, Krug LM. Phase II trial of temozolomide in patients with relapsed sensitive or refractory small cell lung cancer, with assessment of methylguanine-DNA methyltransferase as a potential biomarker. Clin Cancer Res. 2012 Feb 15;18(4):1138-45. Epub 2012 Jan 6. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
# MSKCC 08-065: Zauderer MG, Drilon A, Kadota K, Huberman K, Sima CS, Bergagnini I, Sumner DK, Travis WD, Heguy A, Ginsberg MS, Holodny AI, Riely GJ, Kris MG, Krug LM, Pietanza MC. Trial of a 5-day dosing regimen of temozolomide in patients with relapsed small cell lung cancers with assessment of methylguanine-DNA methyltransferase. Lung Cancer. 2014 Nov;86(2):237-40. Epub 2014 Aug 17. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article EuroPMC NCT00740636
==Topotecan monotherapy==
===Regimen variant #1, 1 mg/m2===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Goto et al. 2016 (JCOG0605)	2007-2012 	Phase 3 (C)	Cisplatin, Etoposide, Irinotecan	Shorter OSMedian OS: 12.5 vs 18.2 mo(HR 1.49, 90% CI 1.14-1.96)
====Chemotherapy====
*Topotecan (Hycamtin) 1 mg/m2 IV over 30 minutes once per day on days 1 to 5
21-day cycle for 4 cycles
===Regimen variant #2, 1.5 mg/m2===
Study 	Dates of enrollment 	Evidence 	Comparator 	Comparative Efficacy
von Pawel et al. 1999 	Not reported 	Phase 3 (E-RT-de-esc)	CAV 	Did not meet co-primary endpoints of ORR/DOR
Eckardt et al. 2007 	1999-2001 	Phase 3 (C) 	Topotecan; oral 	Did not meet primary endpoint of ORR
von Pawel et al. 2014 (ACT-1) 	2007-2010 	Phase 3 (C) 	Amrubicin 	Did not meet primary endpoint of OSMedian OS: 7.8 vs 7.5 mo(HR 1.14, 95% CI 0.94-1.37)
Spigel et al. 2021 (CheckMate 331) 	2015-2017 	Phase 3 (C) 	Nivolumab 	Might have shorter OSMedian OS: 8.4 vs 7.5 mo(HR 1.16, 95% CI 0.96-1.39)
Aix et al. 2022 (ATLANTIS) 	2016-2018 	Phase 3 (C) 	Doxorubicin & Lurbinectedin	Did not meet primary endpoint of OSMedian OS: 7.6 vs 8.6 mo(HR 1.03, 95% CI 0.87-1.22)
Blackhall et al. 2021 (TAHOE) 	2017-04-11 to 2018-12-07	Phase 3 (C) 	Rovalpituzumab tesirine 	Longer OS (primary endpoint)Median OS: 8.6 vs 6.3 mo(HR 0.68, 95% CI 0.55-0.85)
Edelman et al. 2022 (DISTINCT) 	2017 to not reported 	Phase 3 (C) 	1. Irinotecan & Dinutuximab	Did not meet primary endpoint of OSMedian OS: 7.4 vs 6.9 mo
Edelman et al. 2022 (DISTINCT) 	2017 to not reported 	Phase 3 (C) 	2. Irinotecan 	Not reported
Spigel et al. 2024 (RESILIENT Part 2)	2019-08 to 2021-02 	Phase 3 (C) 	Liposomal irinotecan 	Did not meet primary endpoint of OSMedian OS: 8.3 vs 7.9 mo(HR 0.90, 95% CI 0.73-1.11)
Note: In von Pawel et al. 1999 treatment was given until progression of disease, unacceptable toxicity, or 6 cycles beyond maximal response. Patients with stable disease after 4 cycles could have treatment discontinued at physician discretion. In Eckardt et al. 2007, patients with complete or partial response continued treatment until progression of disease or 2 cycles beyond best response. Patients with stable disease received at least 4 cycles therapy. In ACT-1, patients who had at least stable disease by cycle 6 could receive another 6 cycles of treatment.
====Chemotherapy====
*Topotecan (Hycamtin) 1.5 mg/m2 IV over 30 minutes once per day on days 1 to 5
====Supportive therapy====
*(varies depending on reference):
*G-CSF use per physician discretion
*In von Pawel et al. 2014 (ACT-1), "Prophylactic antibiotics were recommended for patients at high risk of infectious complications."
21-day cycle for varying durations: 4 or more cycles (Eckardt et al. 2007); 6 to 12 cycles (ACT-1); indefinitely (ATLANTIS, CheckMate 331, DISTINCT, RESILIENT Part 2, TAHOE); see note (von Pawel et al. 1999) 
===Regimen variant #3, oral route===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Eckardt et al. 2007 	1999-2001 	Phase 3 (E-switch-ic)	Topotecan; IV (1.5 mg/m2)	Did not meet primary endpoint of ORR
O'Brien et al. 2006 (GSK 104864/478)	2000-2004 	Phase 3 (E-esc) 	Best supportive care 	Seems to have longer OS (primary endpoint)
Baize et al. 2020 (GFPC 01-2013) 	2013-2018 	Phase 3 (C) 	Carboplatin & Etoposide 	Shorter PFSMedian PFS: 2.7 vs 4.7 mo(HR 1.75, 90% CI 1.37-2.44)
Spigel et al. 2021 (CheckMate 331) 	2015-2017 	Phase 3 (C) 	Nivolumab 	Might have shorter OSMedian OS: 8.4 vs 7.5 mo(HR 1.16, 95% CI 0.96-1.39)
Note: Duration of treatment details vary depending on reference. In GSK 104864/478, treatment was given for at least 4 cycles, though this depended on tolerability and response. In Eckardt et al. 2007, patients with complete or partial response continued treatment progression of disease or 2 cycles beyond best response. Patients with stable disease received at least 4 cycles of therapy.
====Chemotherapy====
*Topotecan (Hycamtin) 2.3 mg/m2 PO once per day on days 1 to 5
21-day cycle for varying durations: 4 or more cycles (CheckMate 331, Eckardt et al. 2007, GSK 104864/478); 6 cycles (GFPC 01-2013) 
===References===
# von Pawel J, Schiller JH, Shepherd FA, Fields SZ, Kleisbauer JP, Chrysson NG, Stewart DJ, Clark PI, Palmer MC, Depierre A, Carmichael J, Krebs JB, Ross G, Lane SR, Gralla R. Topotecan versus cyclophosphamide, doxorubicin, and vincristine for the treatment of recurrent small-cell lung cancer. J Clin Oncol. 1999 Feb;17(2):658-67. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
# GSK 104864/478: O'Brien ME, Ciuleanu TE, Tsekov H, Shparyk Y, Cuceviá B, Juhasz G, Thatcher N, Ross GA, Dane GC, Crofts T. Phase III trial comparing supportive care alone with supportive care with oral topotecan in patients with relapsed small-cell lung cancer. J Clin Oncol. 2006 Dec 1;24(34):5441-7. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT00276276
# Eckardt JR, von Pawel J, Pujol JL, Papai Z, Quoix E, Ardizzoni A, Poulin R, Preston AJ, Dane G, Ross G. Phase III study of oral compared with intravenous topotecan as second-line therapy in small-cell lung cancer. J Clin Oncol. 2007 May 20;25(15):2086-92. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
# ACT-1: von Pawel J, Jotte R, Spigel DR, O'Brien ME, Socinski MA, Mezger J, Steins M, Bosquée L, Bubis J, Nackaerts K, Trigo JM, Clingan P, Schütte W, Lorigan P, Reck M, Domine M, Shepherd FA, Li S, Renschler MF. Randomized phase III trial of amrubicin versus topotecan as second-line treatment for patients with small-cell lung cancer. J Clin Oncol. 2014 Dec 10;32(35):4012-9. Epub 2014 Nov 10. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT00547651
# JCOG0605: Goto K, Ohe Y, Shibata T, Seto T, Takahashi T, Nakagawa K, Tanaka H, Takeda K, Nishio M, Mori K, Satouchi M, Hida T, Yoshimura N, Kozuki T, Imamura F, Kiura K, Okamoto H, Sawa T, Tamura T; JCOG. Combined chemotherapy with cisplatin, etoposide, and irinotecan versus topotecan alone as second-line treatment for patients with sensitive relapsed small-cell lung cancer (JCOG0605): a multicentre, open-label, randomised phase 3 trial. Lancet Oncol. 2016 Aug;17(8):1147-57. Epub 2016 Jun 14. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC UMIN000000828
#GFPC 01-2013: Baize N, Monnet I, Greillier L, Geier M, Lena H, Janicot H, Vergnenegre A, Crequit J, Lamy R, Auliac JB, Letreut J, Le Caer H, Gervais R, Dansin E, Madroszyk A, Renault PA, Le Garff G, Falchero L, Berard H, Schott R, Saulnier P, Chouaid C; Groupe Français de Pneumo-Cancérologie. Carboplatin plus etoposide versus topotecan as second-line treatment for patients with sensitive relapsed small-cell lung cancer: an open-label, multicentre, randomised, phase 3 trial. Lancet Oncol. 2020 Sep;21(9):1224-1233. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT02738346
# CheckMate 331: Spigel DR, Vicente D, Ciuleanu TE, Gettinger S, Peters S, Horn L, Audigier-Valette C, Pardo Aranda N, Juan-Vidal O, Cheng Y, Zhang H, Shi M, Luft A, Wolf J, Antonia S, Nakagawa K, Fairchild J, Baudelet C, Pandya D, Doshi P, Chang H, Reck M. Second-line nivolumab in relapsed small-cell lung cancer: CheckMate 331. Ann Oncol. 2021 May;32(5):631-641. Epub 2021 Feb 1. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT02481830
#TAHOE: Blackhall F, Jao K, Greillier L, Cho BC, Penkov K, Reguart N, Majem M, Nackaerts K, Syrigos K, Hansen K, Schuette W, Cetnar J, Cappuzzo F, Okamoto I, Erman M, Langer SW, Kato T, Groen H, Sun Z, Luo Y, Tanwani P, Caffrey L, Komarnitsky P, Reinmuth N. Efficacy and Safety of Rovalpituzumab Tesirine Compared With Topotecan as Second-Line Therapy in DLL3-High SCLC: Results From the Phase 3 TAHOE Study. J Thorac Oncol. 2021 Sep;16(9):1547-1558. Epub 2021 Feb 16. link to original article dosing details in abstract have been reviewed by our editors EuroPMC NCT03061812
#DISTINCT: Edelman MJ, Dvorkin M, Laktionov K, Navarro A, Juan-Vidal O, Kozlov V, Golden G, Jordan O, Deng CQ, Bentsion D, Chouaid C, Dechev H, Dowlati A, Fernández Núñez N, Ivashchuk O, Kiladze I, Kortua T, Leighl N, Luft A, Makharadze T, Min Y, Quantin X; DISTINCT study investigators. Randomized phase 3 study of the anti-disialoganglioside antibody dinutuximab and irinotecan vs irinotecan or topotecan for second-line treatment of small cell lung cancer. Lung Cancer. 2022 Apr;166:135-142. Epub 2022 Mar 4. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT03098030
#ATLANTIS: Aix SP, Ciuleanu TE, Navarro A, Cousin S, Bonanno L, Smit EF, Chiappori A, Olmedo ME, Horvath I, Grohé C, Farago AF, López-Vilariño JA, Cullell-Young M, Nieto A, Vasco N, Gómez J, Kahatt C, Zeaiter A, Carcereny E, Roubec J, Syrigos K, Lo G, Barneto I, Pope A, Sánchez A, Kattan J, Zarogoulidis K, Waller CF, Bischoff H, Juan-Vidal O, Reinmuth N, Dómine M, Paz-Ares L. Combination lurbinectedin and doxorubicin versus physician's choice of chemotherapy in patients with relapsed small-cell lung cancer (ATLANTIS): a multicentre, randomised, open-label, phase 3 trial. Lancet Respir Med. 2023 Jan;11(1):74-86. Epub 2022 Oct 14. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT02566993
#RESILIENT Part 2: Spigel DR, Dowlati A, Chen Y, Navarro A, Yang JC, Stojanovic G, Jove M, Rich P, Andric ZG, Wu YL, Rudin CM, Chen H, Zhang L, Yeung S, Benzaghou F, Paz-Ares L, Bunn PA; RESILIENT Trial Investigators. RESILIENT Part 2: A Randomized, Open-Label Phase III Study of Liposomal Irinotecan Versus Topotecan in Adults With Relapsed Small Cell Lung Cancer. J Clin Oncol. 2024 Jul 1;42(19):2317-2326. Epub 2024 Apr 22. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT03088813
==Vinorelbine monotherapy==
===Regimen variant #1, 25 mg/m2===
Study 	Dates of enrollment 	Evidence
Furuse et al. 1996a	Not reported in abstract	Phase 2
Note: The full manuscript was not available for review.
====Chemotherapy====
*Vinorelbine (Navelbine) 25 mg/m2 IV once on day 1
7-day cycles
===Regimen variant #2, 30 mg/m2===
Study 	Dates of enrollment	Evidence
Jassem et al. 1993	1990-06 to 1991-05 	Phase 2
====Chemotherapy====
*Vinorelbine (Navelbine) 30 mg/m2 IV over 20 minutes once on day 1
7-day cycles
===References===
# Jassem J, Karnicka-Mlodkowska H, van Pottelsberghe C, van Glabbeke M, Noseda MA, Ardizzoni A, Gozzelino F, Planting A, van Zandwijk N; EORTC Lung Cancer Cooperative Group. Phase II study of vinorelbine (Navelbine) in previously treated small cell lung cancer patients. Eur J Cancer. 1993;29A(12):1720-2. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
# Furuse K, Kubota K, Kawahara M, Takada M, Kimura I, Fujii M, Ohta M, Hasegawa K, Yoshida K, Nakajima S, Ogura T, Niitani H; Japan Lung Cancer Vinorelbine Study Group. Phase II study of vinorelbine in heavily previously treated small cell lung cancer. Oncology. 1996 Mar-Apr;53(2):169-72. link to original article dosing details in abstract have been reviewed by our editors EuroPMC
Category:Small cell lung cancer regimens
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Category:Lung cancers