Carcinoma of unknown primary

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Carcinoma of unknown primary may also be referred to as carcinoma of unknown primary site, cancer/carcinoma of unknown primary (CUP), occult primary, or unknown primary carcinoma.
Last updated on 2024-09-06:16 regimens on this page
21 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==
*2020: Maghami et al. Diagnosis and Management of Squamous Cell Carcinoma of Unknown Primary in the Head and Neck: ASCO Guideline EuroPMC
==ESMO==
*2023: Krämer et al. Cancer of unknown primary: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up EuroPMC
**2015: Fizazi et al. Cancers of unknown primary site: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up EuroPMC
**2011: Fizazi et al. Cancers of unknown primary site: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up EuroPMC
**2010: Pavlidis et al. Cancers of unknown primary site: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up EuroPMC
**2009: Briasoulis et al. Cancers of unknown primary site: ESMO clinical recommendations for diagnosis, treatment and follow-up EuroPMC
**2008: Briasoulis et al. Cancers of unknown primary site: ESMO clinical recommendation for diagnosis, treatment and follow-up EuroPMC
**2007: Cancers of unknown primary site: ESMO clinical recommendations for diagnosis, treatment and follow-up EuroPMC
**2005: Briasoulis et al. ESMO Minimum Clinical Recommendations for diagnosis, treatment and follow-up of cancers of unknown primary site (CUP) EuroPMC
**2001: ESMO Minimum Clinical Recommendations for diagnosis, treatment and follow-up of cancers of unknown primary site (CUP) EuroPMC
==NCCN==
*NCCN Guidelines - Occult Primary
**2014: Ettinger et al. Occult Primary, Version 3.2014 EuroPMC
**2011: Ettinger et al. NCCN Clinical Practice Guidelines Occult primary. EuroPMC
**2005: Ettinger et al. Occult primary cancer clinical practice guidelines. EuroPMC
=All lines of therapy=
==BEP==
BEP: Bleomycin, Etoposide, Platinol (Cisplatin)
PEB: Platinol (Cisplatin), Etoposide, Bleomycin
===Regimen===
Study 	Dates of enrollment	Evidence
Hainsworth et al 1992	1978-02 to 1989-12 	Phase 2
====Chemotherapy====
*Bleomycin (Blenoxane) 30 units IV once per day on days 1, 8, 15
*Etoposide (Vepesid) 100 mg/m2 IV once per day on days 1 to 5
*Cisplatin (Platinol) 20 mg/m2 IV once per day on days 1 to 5
21-day cycles
===References===
# Hainsworth JD, Johnson DH, Greco FA. Cisplatin-based combination chemotherapy in the treatment of poorly differentiated carcinoma and poorly differentiated adenocarcinoma of unknown primary site: results of a 12-year experience. J Clin Oncol. 1992 Jun;10(6):912-22. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
==Carboplatin & Docetaxel (DCb)==
===Regimen variant #1===
Study 	Dates of enrollment 	Evidence
Pentheroudakis et al. 2008	2000-01 to not reported	Phase 2
====Chemotherapy====
*Carboplatin (Paraplatin) AUC 5 IV over 30 minutes once on day 1, given second
*Docetaxel (Taxotere) 75 mg/m2 IV over 30 minutes once on day 1, given first
====Supportive therapy====
*Dexamethasone (Decadron) 8 mg PO twice per day on day -1, then 16 mg IV once on day 1, prior to chemotherapy
*Ondansetron (Zofran) 8 mg IV once on day 1, prior to chemotherapy
*Ranitidine (Zantac) 100 mg IV once on day 1, prior to chemotherapy
*Dimetindene (Fenistil) 0.1 mg/kg (route unclear) prior to chemotherapy
21-day cycle for up to 8 cycles
===Regimen variant #2===
Study 	Dates of enrollment	Evidence
Greco et al. 2000 Study A	1996-11 to 1997-08 	Phase 2
====Chemotherapy====
*Carboplatin (Paraplatin) AUC 6 IV over 20 minutes once on day 1, given second
*Docetaxel (Taxotere) 65 mg/m2 IV over 60 minutes once on day 1, given first
====Supportive therapy====
*Dexamethasone (Decadron) 8 mg PO twice per day on days -1 to 2
*One of the following serotonin 5-HT3 antagonists:
**Ondansetron (Zofran) 32 mg IV once on day 1; 15 minutes prior to chemotherapy
**Granisetron 10 mcg/kg IV once on day 1; 15 minutes prior to chemotherapy
21-day cycle for 4 to 8 cycles
===References===
# Greco FA, Erland JB, Morrissey LH, Burris HA 3rd, Hermann RC, Steis R, Thompson D, Gray J, Hainsworth JD. Carcinoma of unknown primary site: phase II trials with docetaxel plus cisplatin or carboplatin. Ann Oncol. 2000 Feb;11(2):211-5. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
# Pentheroudakis G, Briasoulis E, Kalofonos HP, Fountzilas G, Economopoulos T, Samelis G, Koutras A, Karina M, Xiros N, Samantas E, Bamias A, Pavlidis N; Hellenic Cooperative Oncology Group. Docetaxel and carboplatin combination chemotherapy as outpatient palliative therapy in carcinoma of unknown primary: a multicentre Hellenic Cooperative Oncology Group phase II study. Acta Oncol. 2008;47(6):1148-55. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
==Carboplatin & Gemcitabine (GCb)==
GCb Gemcitabine & Carboplatin
===Regimen===
Study 	Dates of enrollment 	Evidence
Krämer et al. 2024 (CUPISCO)	2018-07-10 to 2022-12-09	Non-randomized portion of phase 2 RCT
====Chemotherapy====
*Carboplatin (Paraplatin) AUC 5 to 6 IV once on day 1
*Gemcitabine (Gemzar) 1000 mg/m2 IV once per day on days 1 & 8
21-day cycle for 3 cycles
====Subsequent treatment====
*GCb continuation versus molecularly-guided thereapy
===References===
#CUPISCO: Krämer A, Bochtler T, Pauli C, Shiu KK, Cook N, de Menezes JJ, Pazo-Cid RA, Losa F, Robbrecht DG, Tomášek J, Arslan C, Özgüroğlu M, Stahl M, Bigot F, Kim SY, Naito Y, Italiano A, Chalabi N, Durán-Pacheco G, Michaud C, Scarato J, Thomas M, Ross JS, Moch H, Mileshkin L. Molecularly guided therapy versus chemotherapy after disease control in unfavourable cancer of unknown primary (CUPISCO): an open-label, randomised, phase 2 study. Lancet. 2024 Aug 10;404(10452):527-539. Epub 2024 Jul 31. link to original article dosing details in supplement have been reviewed by our editors EuroPMC NCT03498521
==Carboplatin & Gemcitabine (GCb) & Paclitaxel==
GCP: Gemcitabine, Carboplatin, Paclitaxel
===Regimen===
Study 	Dates of enrollment	Evidence
Greco et al. 2002	1998-12 to 2000-08 	Phase 2
====Chemotherapy====
*Gemcitabine (Gemzar) 1000 mg/m2 IV once per day on days 1 & 8
*Carboplatin (Paraplatin) AUC 5 IV over 20 to 30 minutes once on day 1
*Paclitaxel (Taxol) 200 mg/m2 IV over 60 minutes once on day 1
====Supportive therapy====
*Corticosteroids IV once on day 1; 30 minutes prior to paclitaxel
*Diphenhydramine (Benadryl) 50 mg IV once on day 1; 30 minutes prior to paclitaxel
*Cimetidine (Tagamet) 300 mg IV once on day 1; 30 minutes prior to paclitaxel
21-day cycles
===References===
# Greco FA, Burris HA 3rd, Litchy S, Barton JH, Bradof JE, Richards P, Scullin DC Jr, Erland JB, Morrissey LH, Hainsworth JD. Gemcitabine, carboplatin, and paclitaxel for patients with carcinoma of unknown primary site: a Minnie Pearl Cancer Research Network study. J Clin Oncol. 2002 Mar 15;20(6):1651-6. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
==Carboplatin & Paclitaxel (CP)==
===Regimen variant #1, q3wk x 3===
Study 	Dates of enrollment 	Evidence
Krämer et al. 2024 (CUPISCO)	2018-07-10 to 2022-12-09	Non-randomized portion of phase 2 RCT
====Chemotherapy====
*Carboplatin (Paraplatin) AUC 5 or 6 IV once on day 1
*Paclitaxel (Taxol) 175 mg/m2 IV once on day 1
21-day cycle for 3 cycles
====Subsequent treatment====
*CP continuation versus molecularly-guided thereapy
===Regimen variant #2, weekly x 9===
Study 	Dates of enrollment 	Evidence
Krämer et al. 2024 (CUPISCO)	2018-07-10 to 2022-12-09	Non-randomized portion of phase 2 RCT
====Chemotherapy====
*Carboplatin (Paraplatin) AUC 2 IV once on day 1 
*Paclitaxel (Taxol) 60 mg/m2 IV once on day 1
7-day cycle for 9 cycles
====Subsequent treatment====
*CP continuation versus molecularly-guided thereapy
===Regimen variant #3===
Study 	Dates of enrollment	Evidence
Briasoulis et al. 2000	1996-02 to 1999-02 	Phase 2
Hayashi et al. 2019 	2008-10 to 2015-02 	Phase 2
====Chemotherapy====
*Carboplatin (Paraplatin) AUC 6 IV over 30 minutes once on day 1, given first
*Paclitaxel (Taxol) 200 mg/m2 IV over 3 hours once on day 1, given second
====Supportive therapy====
per Briasoulis 2000 study
*Methylprednisolone (Solumedrol) 32 mg PO for three doses, 24 and 12 hours before paclitaxel, and 10 minutes before carboplatin
*Dexamethasone (Decadron) 16 mg IV once on day 1, at least 10 minutes prior to chemotherapy
*One of the following antihistamines:
**Diphenhydramine (Benadryl) 50 mg IV once on day 1, at least 10 minutes prior to chemotherapy
**Dimetindene (Fenistil) 0.1 mg/kg IV once on day 1, at least 10 minutes prior to chemotherapy
*Ranitidine (Zantac) 100 mg IV once on day 1, at least 10 minutes prior to chemotherapy
*Ondansetron (Zofran) 8 mg IV once on day 1, after the above premedications
*Suggested: Filgrastim (Neupogen) 300 mcg SC once per day on days 5 to 12
21-day cycle for 6 to 8 cycles
===References===
# Briasoulis E, Kalofonos H, Bafaloukos D, Samantas E, Fountzilas G, Xiros N, Skarlos D, Christodoulou C, Kosmidis P, Pavlidis N; Hellenic Cooperative Oncology Group. Carboplatin plus paclitaxel in unknown primary carcinoma: a phase II Hellenic Cooperative Oncology Group Study. J Clin Oncol. 2000 Sep;18(17):3101-7. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
# Hayashi H, Kurata T, Takiguchi Y, Arai M, Takeda K, Akiyoshi K, Matsumoto K, Onoe T, Mukai H, Matsubara N, Minami H, Toyoda M, Onozawa Y, Ono A, Fujita Y, Sakai K, Koh Y, Takeuchi A, Ohashi Y, Nishio K, Nakagawa K. Randomized Phase II Trial Comparing Site-Specific Treatment Based on Gene Expression Profiling With Carboplatin and Paclitaxel for Patients With Cancer of Unknown Primary Site. J Clin Oncol. 2019 Mar 1;37(7):570-579. Epub 2019 Jan 17. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
#CUPISCO: Krämer A, Bochtler T, Pauli C, Shiu KK, Cook N, de Menezes JJ, Pazo-Cid RA, Losa F, Robbrecht DG, Tomášek J, Arslan C, Özgüroğlu M, Stahl M, Bigot F, Kim SY, Naito Y, Italiano A, Chalabi N, Durán-Pacheco G, Michaud C, Scarato J, Thomas M, Ross JS, Moch H, Mileshkin L. Molecularly guided therapy versus chemotherapy after disease control in unfavourable cancer of unknown primary (CUPISCO): an open-label, randomised, phase 2 study. Lancet. 2024 Aug 10;404(10452):527-539. Epub 2024 Jul 31. link to original article dosing details in supplement have been reviewed by our editors EuroPMC NCT03498521
==Cisplatin monotherapy==
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Gross-Goupil et al. 2012 (GEFCAPI 02)	2003-2007 	Randomized Phase 2 (C)	Cisplatin & Gemcitabine	Did not meet primary endpoint of OS
Note: to our knowledge, this regimen was not tested as an experimental arm in an RCT in this context, prior to becoming a standard comparator arm.
====Chemotherapy====
*Cisplatin (Platinol) 100 mg/m2 IV once on day 1
21-day cycles
===References===
# GEFCAPI 02: Gross-Goupil M, Fourcade A, Blot E, Penel N, Négrier S, Culine S, Chaigneau L, Lesimple T, Priou F, Lortholary A, Kaminsky MC, Provencal J, Voog E, Bouzy J, Laplanche A, Fizazi K. Cisplatin alone or combined with gemcitabine in carcinomas of unknown primary: results of the randomised GEFCAPI 02 trial. Eur J Cancer. 2012 Mar;48(5):721-7. Epub 2012 Feb 6. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT00126269
==Cisplatin & Docetaxel (DC)==
===Regimen===
Study 	Dates of enrollment	Evidence
Greco et al. 2000 Study B	1997-09 to 1998-10 	Phase 2
====Chemotherapy====
*Cisplatin (Platinol) 75 mg/m2 IV over 60 minutes once on day 1
*Docetaxel (Taxotere) 75 mg/m2 IV over 60 minutes once on day 1
====Supportive therapy====
*Dexamethasone (Decadron) 8 mg PO twice per day on days -1 to 2
**Suggested: 20 mg IV once on day 1; 15 minutes prior to cisplatin
*2 liters of normal saline with chemotherapy
*One of the following serotonin 5-HT3 antagonists:
**Ondansetron (Zofran) 32 mg IV once on day 1; 15 minutes prior to cisplatin
**Granisetron 10 mcg/kg IV once on day 1; 15 minutes prior to cisplatin
*Ondansetron (Zofran) 8 mg PO three times per day on days 2 to 6
21-day cycle for up to 8 cycles
===References===
# Greco FA, Erland JB, Morrissey LH, Burris HA 3rd, Hermann RC, Steis R, Thompson D, Gray J, Hainsworth JD. Carcinoma of unknown primary site: phase II trials with docetaxel plus cisplatin or carboplatin. Ann Oncol. 2000 Feb;11(2):211-5. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
==Cisplatin & Gemcitabine (GC)==
GC: Gemcitabine & Cisplatin
===Regimen variant #1, cisplatin on day 1===
Study 	Dates of enrollment 	Evidence
Krämer et al. 2024 (CUPISCO)	2018-07-10 to 2022-12-09	Non-randomized portion of phase 2 RCT
====Chemotherapy====
*Cisplatin (Platinol) 60 to 75 mg/m2 IV once on day 1
*Gemcitabine (Gemzar) 1000 mg/m2 IV once per day on days 1 & 8
21-day cycle for 3 cycles
====Subsequent treatment====
*GC continuation versus molecularly-guided thereapy
===Regimen variant #2, split-dose cisplatin===
Study 	Dates of enrollment 	Evidence
Krämer et al. 2024 (CUPISCO)	2018-07-10 to 2022-12-09	Non-randomized portion of phase 2 RCT
====Chemotherapy====
*Cisplatin (Platinol) 25 mg/m2 IV once per day on days 1 & 8
*Gemcitabine (Gemzar) 1000 mg/m2 IV once per day on days 1 & 8
21-day cycle for 3 cycles
====Subsequent treatment====
*GC continuation versus molecularly-guided thereapy
===Regimen variant #3===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Culine et al. 2003 (GEFCAPI 01) 	1999-2000 	Randomized Phase 2 (E-switch-ic)	Cisplatin & Irinotecan	Not reported
Gross-Goupil et al. 2012 (GEFCAPI 02)	2003-2007 	Randomized Phase 2 (E-esc) 	Cisplatin 	Did not meet primary endpoint of OS
====Chemotherapy====
*Cisplatin (Platinol) 100 mg/m2 IV once on day 1
*Gemcitabine (Gemzar) 1250 mg/m2 IV once per day on days 1 & 8
21-day cycles
===References===
# GEFCAPI 01: Culine S, Lortholary A, Voigt JJ, Bugat R, Théodore C, Priou F, Kaminsky MC, Lesimple T, Pivot X, Coudert B, Douillard JY, Merrouche Y, Allouache J, Goupil A, Négrier S, Viala J, Petrow P, Bouzy J, Laplanche A, Fizazi K; Trial for the French Study Group on Carcinomas of Unknown Primary (GEFCAPI 01). Cisplatin in combination with either gemcitabine or irinotecan in carcinomas of unknown primary site: results of a randomized phase II study--trial for the French Study Group on Carcinomas of Unknown Primary (GEFCAPI 01). J Clin Oncol. 2003 Sep 15;21(18):3479-82. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC content property of HemOnc.org 
# GEFCAPI 02: Gross-Goupil M, Fourcade A, Blot E, Penel N, Négrier S, Culine S, Chaigneau L, Lesimple T, Priou F, Lortholary A, Kaminsky MC, Provencal J, Voog E, Bouzy J, Laplanche A, Fizazi K. Cisplatin alone or combined with gemcitabine in carcinomas of unknown primary: results of the randomised GEFCAPI 02 trial. Eur J Cancer. 2012 Mar;48(5):721-7. Epub 2012 Feb 6. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT00126269
#CUPISCO: Krämer A, Bochtler T, Pauli C, Shiu KK, Cook N, de Menezes JJ, Pazo-Cid RA, Losa F, Robbrecht DG, Tomášek J, Arslan C, Özgüroğlu M, Stahl M, Bigot F, Kim SY, Naito Y, Italiano A, Chalabi N, Durán-Pacheco G, Michaud C, Scarato J, Thomas M, Ross JS, Moch H, Mileshkin L. Molecularly guided therapy versus chemotherapy after disease control in unfavourable cancer of unknown primary (CUPISCO): an open-label, randomised, phase 2 study. Lancet. 2024 Aug 10;404(10452):527-539. Epub 2024 Jul 31. link to original article dosing details in supplement have been reviewed by our editors EuroPMC NCT03498521
==Cisplatin & Irinotecan (IC)==
IC: Irinotecan & Cisplatin
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Culine et al. 2003 (GEFCAPI 01)	1999-2000 	Randomized Phase 2 (E-switch-ic)	Cisplatin & Gemcitabine	Not reported
====Chemotherapy====
*Cisplatin (Platinol) 80 mg/m2 IV once on day 1
*Irinotecan (Camptosar) 150 mg/m2 IV once on day 1
21-day cycles
===References===
# GEFCAPI 01: Culine S, Lortholary A, Voigt JJ, Bugat R, Théodore C, Priou F, Kaminsky MC, Lesimple T, Pivot X, Coudert B, Douillard JY, Merrouche Y, Allouache J, Goupil A, Négrier S, Viala J, Petrow P, Bouzy J, Laplanche A, Fizazi K; Trial for the French Study Group on Carcinomas of Unknown Primary (GEFCAPI 01). Cisplatin in combination with either gemcitabine or irinotecan in carcinomas of unknown primary site: results of a randomized phase II study--trial for the French Study Group on Carcinomas of Unknown Primary (GEFCAPI 01). J Clin Oncol. 2003 Sep 15;21(18):3479-82. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
==DCF==
DCF: Docetaxel, Cisplatin, Fluorouracil
===Regimen===
Note: Various guidelines list this as a suitable regimen in this setting, but we are not aware of any specific protocols for this setting.
====Chemotherapy====
*Docetaxel (Taxotere) 75 mg/m2 IV once on day 1
*Cisplatin (Platinol) 75 mg/m2 IV once on day 1
*Fluorouracil (5-FU) 750 mg/m2/day IV continuous infusion over 120 hours, started on day 1 (total dose per cycle: 3750 mg/m2)
====Supportive therapy====
*1 liter normal saline before and after cisplatin +/- mannitol, potassium chloride, magnesium sulfate
*Dexamethasone (Decadron) 8 mg PO once per day the day before, the day of, and day after chemotherapy
*Ciprofloxacin (Cipro) 1000 mg PO (reference did not specify, but assume 500 mg twice per day) on days 5 to 15
21-day cycle for 3 cycles
===References===
# None that we are aware of
==Docetaxel & Gemcitabine==
===Regimen===
Study 	Dates of enrollment	Evidence
Pouessel et al. 2004	2000-12 to 2003-04 	Phase 2
====Chemotherapy====
*Docetaxel (Taxotere) 75 mg/m2 IV over 60 minutes once on day 8
*Gemcitabine (Gemzar) 1000 mg/m2 IV over 30 minutes once per day on days 1 & 8
====Supportive therapy====
*Corticosteroids PO the day before, the day of, and day after docetaxel
21-day cycle for up to 6 cycles
===References===
# Pouessel D, Culine S, Becht C, Ychou M, Romieu G, Fabbro M, Cupissol D, Pinguet F. Gemcitabine and docetaxel as front-line chemotherapy in patients with carcinoma of an unknown primary site. Cancer. 2004 Mar 15;100(6):1257-61. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
==Erlotinib & Bevacizumab==
===Regimen===
Study 	Dates of enrollment	Evidence
Hainsworth et al. 2007a	2004-04 to 2005-07 	Phase 2
====Targeted therapy====
*Erlotinib (Tarceva) 150 mg PO once per day on days 1 to 28
*Bevacizumab (Avastin) 10 mg/kg IV once per day on days 1 & 15
**Infusion time is 90 minutes for the first dose, then if tolerated, 60 minutes for the second dose, and 30 minutes for the third dose and later 
28-day cycles
===References===
# Hainsworth JD, Spigel DR, Farley C, Thompson DS, Shipley DL, Greco FA; Minnie Pearl Cancer Research Network. Phase II trial of bevacizumab and erlotinib in carcinomas of unknown primary site: the Minnie Pearl Cancer Research Network. J Clin Oncol. 2007 May 1;25(13):1747-52. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
==Gemcitabine & Irinotecan==
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator	Comparative Efficacy
Hainsworth et al. 2010 (SCRI UNKPRI 12)	2003-2008 	Phase 3 (E-switch-ic)	PCE 	Did not meet primary endpoint of OS24
====Chemotherapy====
*Gemcitabine (Gemzar) 1000 mg/m2 IV once per day on days 1 & 8
*Irinotecan (Camptosar) 100 mg/m2 IV once per day on days 1 & 8
21-day cycle for up to 6 cycles
===References===
# SCRI UNKPRI 12: Hainsworth JD, Spigel DR, Clark BL, Shipley D, Thompson DS, Farley C, West-Osterfield K, Lane CM, Cescon T, Bury MJ, Greco FA. Paclitaxel/carboplatin/etoposide versus gemcitabine/irinotecan in the first-line treatment of patients with carcinoma of unknown primary site: a randomized, phase III Sarah Cannon Oncology Research Consortium Trial. Cancer J. 2010 Jan-Feb;16(1):70-5. link to original article EuroPMC NCT00193596
==Nivolumab monotherapy==
===Regimen===
Study 	Dates of enrollment 	Evidence
Tanizaki et al. 2021	2018-02-19 to 2019-08-09	Phase 2 (RT)
Note: This was the trial supporting PMDA approval for this indication.
====Immunotherapy====
*Nivolumab (Opdivo) 240 mg IV once on day 1
14-day cycle for up to 52 cycles (2 years)
===References===
#Tanizaki J, Yonemori K, Akiyoshi K, Minami H, Ueda H, Takiguchi Y, Miura Y, Segawa Y, Takahashi S, Iwamoto Y, Kidera Y, Fukuoka K, Ito A, Chiba Y, Sakai K, Nishio K, Nakagawa K, Hayashi H. Open-label phase II study of the efficacy of nivolumab for cancer of unknown primary. Ann Oncol. 2022 Feb;33(2):216-226. Epub 2021 Nov 26. link to original article EuroPMC UMIN000030649
==PCE==
PCE: Paclitaxel, Carboplatin, Etoposide
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Greco et al. 2000a 	1995-1996 	Phase 2 	 	
Hainsworth et al. 2010 (SCRI UNKPRI 12)	2003-2008 	Phase 3 (E-switch-ic)	Gemcitabine & Irinotecan	Did not meet primary endpoint of OS24
====Chemotherapy====
*Paclitaxel (Taxol) 200 mg/m2 IV over 60 minutes once on day 1
*Carboplatin (Paraplatin) AUC 6 IV over 20 to 30 minutes once on day 1
*Etoposide (Vepesid) as follows:
**Days 1, 3, 5, 7, 9: 50 mg PO once per day
**Days 2, 4, 6, 8, 10: 100 mg PO once per day
====Supportive therapy====
*Dexamethasone (Decadron) 20 mg PO for two doses, 12 hours and 4 hours prior to paclitaxel
*Dexamethasone (Decadron) 20 mg IV once on day 1; 30 minutes prior to paclitaxel
*Diphenhydramine (Benadryl) 50 mg IV once on day 1; 30 minutes prior to paclitaxel
*Cimetidine (Tagamet) 300 mg IV once on day 1; 30 minutes prior to paclitaxel
21-day cycle for 4 to 8 cycles
===References===
# Greco FA, Burris HA 3rd, Erland JB, Gray JR, Kalman LA, Schreeder MT, Hainsworth JD. Carcinoma of unknown primary site. Cancer. 2000 Dec 15;89(12):2655-60. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
# SCRI UNKPRI 12: Hainsworth JD, Spigel DR, Clark BL, Shipley D, Thompson DS, Farley C, West-Osterfield K, Lane CM, Cescon T, Bury MJ, Greco FA. Paclitaxel/carboplatin/etoposide versus gemcitabine/irinotecan in the first-line treatment of patients with carcinoma of unknown primary site: a randomized, phase III Sarah Cannon Oncology Research Consortium Trial. Cancer J. 2010 Jan-Feb;16(1):70-5. link to original article EuroPMC NCT00193596
==PCF==
PCF: Paclitaxel, Cisplatin, Fluorouracil
===Regimen===
Note: Various guidelines list this as a suitable regimen in this setting, but we are not aware of any specific protocols for this setting.
====Chemotherapy====
*Paclitaxel (Taxol) 175 mg/m2 IV over 3 hours once on day 1
*Cisplatin (Platinol) 100 mg/m2 IV once on day 2
*Fluorouracil (5-FU) 500 mg/m2/day IV continuous infusion over 120 hours, started on day 2 (total dose per cycle: 2500 mg/m2)
21-day cycle for 3 cycles
===References===
# None that we are aware of
Category:Carcinoma of unknown primary regimens
Category:Site-agnostic regimens
Category:Malignant solid neoplasm