Thymoma

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Last updated on 2024-07-23:14 regimens on this page
16 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.
==ESMO==
*2015: Girard et al. Thymic epithelial tumours: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up EuroPMC
==NCCN==
*NCCN Guidelines - Thymomas and Thymic Carcinomas
=Neoadjuvant therapy for borderline resectable disease=
==PAC-P==
PAC: Platinol (Cisplatin), Adriamycin (Doxorubicin), Cyclophosphamide
CAP: Cyclophosphamide, Adriamycin (Doxorubicin), Platinol (Cisplatin)
===Regimen===
Study 	Dates of enrollment	Evidence
Kim et al. 2004	1990-02 to 2000-04 	Phase 2
Note: while this regimen is conventionally referred to as PAC or CAP, it also includes a high-dose prednisone component with likely antineoplastic properties, and has been renamed PAC-P here.
====Chemotherapy====
*Cisplatin (Platinol) 30 mg/m2 IV once per day on days 1 to 3
*Doxorubicin (Adriamycin) 20 mg/m2/day IV continuous infusion over 72 hours, started on day 1 (total dose per cycle: 60 mg/m2)
*Cyclophosphamide (Cytoxan) 500 mg/m2 IV slow push once on day 1
====Glucocorticoid therapy====
*Prednisone (Sterapred) 100 mg PO once per day on days 1 to 5
====Supportive therapy====
*Metoclopramide (Reglan) 1 mg/kg IV once per day on days 1 to 3, prior to chemotherapy
*Diphenhydramine (Benadryl) 25 mg IV once per day on days 1 to 3, prior to chemotherapy
21- to 28-day cycle for 3 cycles
====Subsequent treatment====
*Surgical resection is performed if CT scan 3 to 4 weeks after the third cycle of chemotherapy shows disease amenable to resection, and is followed by adjuvant RT, then PAC consolidation
===References===
# Kim ES, Putnam JB, Komaki R, Walsh GL, Ro JY, Shin HJ, Truong M, Moon H, Swisher SG, Fossella FV, Khuri FR, Hong WK, Shin DM. Phase II study of a multidisciplinary approach with induction chemotherapy, followed by surgical resection, radiation therapy, and consolidation chemotherapy for unresectable malignant thymomas: final report. Lung Cancer. 2004 Jun;44(3):369-79. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
=Adjuvant therapy=
==PAC-P==
PAC: Platinol (Cisplatin), Adriamycin (Doxorubicin), Cyclophosphamide
CAP: Cyclophosphamide, Adriamycin (Doxorubicin), Platinol (Cisplatin)
===Regimen===
Study 	Dates of enrollment	Evidence
Kim et al. 2004	1990-02 to 2000-04 	Phase 2
Note: while this regimen is conventionally referred to as PAC or CAP, it also includes a high-dose prednisone component with likely antineoplastic properties, and has been renamed PAC-P, here. Also note that these doses are 80% of the induction doses, except for the prednisone.
====Preceding treatment====
*Definitive RT
====Chemotherapy====
*Cisplatin (Platinol) 24 mg/m2 IV once per day on days 1 to 3
*Doxorubicin (Adriamycin) 16 mg/m2/day IV continuous infusion over 72 hours, started on day 1 (total dose per cycle: 48 mg/m2)
*Cyclophosphamide (Cytoxan) 400 mg/m2 IV slow push once on day 1
====Glucocorticoid therapy====
*Prednisone (Sterapred) 100 mg PO once per day on days 1 to 5
21- to 28-day cycle for 3 cycles
===References===
# Kim ES, Putnam JB, Komaki R, Walsh GL, Ro JY, Shin HJ, Truong M, Moon H, Swisher SG, Fossella FV, Khuri FR, Hong WK, Shin DM. Phase II study of a multidisciplinary approach with induction chemotherapy, followed by surgical resection, radiation therapy, and consolidation chemotherapy for unresectable malignant thymomas: final report. Lung Cancer. 2004 Jun;44(3):369-79. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
==Radiation therapy==
===Regimen===
Study 	Dates of enrollment	Evidence
Kim et al. 2004	1990-02 to 2000-04 	Phase 2
====Preceding treatment====
*PAC-P induction, then surgery (in some cases)
====Radiotherapy====
*External beam radiotherapy by the following response-based criteria:
*If tumor is completely resected and has at least 80% necrosis: 5000 cGy is administered 3 to 6 weeks after surgery
*If tumor is incompletely resected or has less than 80% necrosis: 6000 cGy is administered
One course
====Subsequent treatment====
*Adjuvant PAC-P x 3
===References===
# Kim ES, Putnam JB, Komaki R, Walsh GL, Ro JY, Shin HJ, Truong M, Moon H, Swisher SG, Fossella FV, Khuri FR, Hong WK, Shin DM. Phase II study of a multidisciplinary approach with induction chemotherapy, followed by surgical resection, radiation therapy, and consolidation chemotherapy for unresectable malignant thymomas: final report. Lung Cancer. 2004 Jun;44(3):369-79. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
=Advanced or metastatic disease, first-line therapy=
==ADOC==
ADOC: Adriamycin (Doxorubicin), cis-Diamminedichloroplatinum (Cisplatin), Oncovin (Vincristine), Cyclophosphamide
===Regimen===
Study 	Dates of enrollment	Evidence
Fornasiero et al. 1991	1977-1990 	Retrospective
Note: The body of Fornasiero et al. 1991 specifies that cycles are given every 3 weeks. However, the abstract says that cycles are given "at monthly intervals," and some guidelines list the regimen as being given every 4 weeks.
====Chemotherapy====
*Doxorubicin (Adriamycin) 40 mg/m2 IV once on day 1
*Cisplatin (Platinol) 50 mg/m2 IV once on day 1
*Vincristine (Oncovin) 0.6 mg/m2 IV once on day 3
*Cyclophosphamide (Cytoxan) 700 mg/m2 IV once on day 4
21- to 28-day cycles
===References===
# Retrospective: Fornasiero A, Daniele O, Ghiotto C, Piazza M, Fiore-Donati L, Calabró F, Rea F, Fiorentino MV. Chemotherapy for invasive thymoma: A 13-year experience. Cancer. 1991 Jul 1;68(1):30-3. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
==Carboplatin & Paclitaxel (CP)==
===Regimen===
Study 	Dates of enrollment	Evidence
Lemma et al. 2011	2001-02 to 2008-01 	Phase 2
====Chemotherapy====
*Carboplatin (Paraplatin) AUC 6 IV over 30 minutes once on day 1, given second
*Paclitaxel (Taxol) 225 mg/m2 IV over 3 hours once on day 1, given first
====Supportive therapy====
*Cimetidine (Tagamet) 300 mg IV once on day 1; 60 minutes prior to paclitaxel 
*Diphenhydramine (Benadryl) 25 mg IV once on day 1; 60 minutes prior to paclitaxel 
*Dexamethasone (Decadron) 20 mg IV once on day 1; 60 minutes prior to paclitaxel 
21-day cycle for up to 6 cycles
===References===
# Lemma GL, Lee JW, Aisner SC, Langer CJ, Tester WJ, Johnson DH, Loehrer PJ Sr. Phase II study of carboplatin and paclitaxel in advanced thymoma and thymic carcinoma. J Clin Oncol. 2011 May 20;29(15):2060-5. Epub 2011 Apr 18. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article EuroPMC
==CISCA==
CISCA: CISplatin, Cyclophosphamide, Adriamycin (Doxorubicin)
PAC: Platinol (Cisplatin), Adriamycin (Doxorubicin), Cyclophosphamide
CAP: Cyclophosphamide, Adriamycin (Doxorubicin), Platinol (Cisplatin)
===Regimen===
Study 	Dates of enrollment	Evidence
Loehrer et al. 1990	1983-04 to 1988-03 	Phase 2
====Chemotherapy====
*Cisplatin (Platinol) 50 mg/m2 IV over at least 1 hour once on day 1
*Doxorubicin (Adriamycin) 50 mg/m2 IV slow push once on day 1
*Cyclophosphamide (Cytoxan) 500 mg/m2 IV slow push once on day 1
====Supportive therapy====
*1 liter NS over 2 hours at least 2 hours before and after cisplatin therapy
*Corticosteroids use for antiemesis was specifically discouraged unless the indication was for myasthenia gravis
21-day cycle for up to 8 cycles
===References===
# Loehrer PJ Sr, Perez CA, Roth LM, Greco A, Livingston RB, Einhorn LH. Chemotherapy for advanced thymoma: preliminary results of an intergroup study. Ann Intern Med. 1990 Oct 1;113(7):520-4. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
## Update: Loehrer PJ Sr, Kim K, Aisner SC, Livingston R, Einhorn LH, Johnson D, Blum R; Eastern Cooperative Oncology Group; Southwest Oncology Group; Southeastern Cancer Study Group. Cisplatin plus doxorubicin plus cyclophosphamide in metastatic or recurrent thymoma: final results of an intergroup trial. J Clin Oncol. 1994 Jun;12(6):1164-8. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
==Cisplatin & Etoposide (EP)==
PE: Platinol (Cisplatin), Etoposide
===Regimen===
Study 	Dates of enrollment	Evidence
Giaccone et al. 1996	1985-09 to 1991-08 	Phase 2
====Chemotherapy====
*Cisplatin (Platinol) 60 mg/m2 IV over 60 minutes once on day 1
*Etoposide (Vepesid) 120 mg/m2 IV over at least 30 minutes once per day on days 1 to 3
====Supportive therapy====
*"A program of forced hydration"
21-day cycle for up to 8 cycles
===References===
# Giaccone G, Ardizzoni A, Kirkpatrick A, Clerico M, Sahmoud T, van Zandwijk N; EORTC Lung Cancer Cooperative Group. Cisplatin and etoposide combination chemotherapy for locally advanced or metastatic thymoma: a phase II study of the European Organisation for Research and Treatment of Cancer Lung Cancer Cooperative Group. J Clin Oncol. 1996 Mar;14(3):814-20. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
==VIP==
VIP: Vepesid (Etoposide), Ifosfamide, Platinol (Cisplatin)
===Regimen===
Study 	Dates of enrollment	Evidence
Loehrer et al. 2001	1995-07 to 1997-02 	Phase 2
====Chemotherapy====
*Etoposide (Vepesid) 75 mg/m2 IV once per day on days 1 to 4
*Ifosfamide (Ifex) 1200 mg/m2 IV once per day on days 1 to 4
*Cisplatin (Platinol) 20 mg/m2 IV once per day on days 1 to 4
====Supportive therapy====
*Mesna (Mesnex) 240 mg/m2 IV push two times per day on days 1 to 4, given 4 hours after and 8 hours after ifosfamide (total dose per cycle: 1920 mg/m2)
*1 liter normal saline once per day on days 1 to 4, prior to cisplatin
*Filgrastim (Neupogen) 5 mcg/kg SC once per day on days 5 to 15, until WBC count at least 10 x 109/L above nadir
21-day cycle for 4 cycles
===References===
# Loehrer PJ Sr, Jiroutek M, Aisner S, Aisner J, Green M, Thomas CR Jr, Livingston R, Johnson DH. Combined etoposide, ifosfamide, and cisplatin in the treatment of patients with advanced thymoma and thymic carcinoma: an intergroup trial. Cancer. 2001 Jun 1;91(11):2010-5. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
=Advanced or metastatic disease, subsequent lines of therapy=
==Capecitabine & Gemcitabine==
CAP-GEM: CAPecitabine & GEMcitabine
===Regimen===
Study 	Dates of enrollment	Evidence	Efficacy
Palmieri et al. 2009	2005-11 to 2008-08 	Phase 2 	ORR: 40%
====Chemotherapy====
*Capecitabine (Xeloda) 650 mg/m2 PO twice per day on days 1 to 14
*Gemcitabine (Gemzar) 1000 mg/m2 IV once per day on days 1 & 8
21-day cycles
===References===
# Palmieri G, Merola G, Federico P, Petillo L, Marino M, Lalle M, Milella M, Ceribelli A, Montella L, Merola C, Del Prete S, Bergaglio M, De Placido S, Di Lorenzo G. Preliminary results of phase II study of capecitabine and gemcitabine (CAP-GEM) in patients with metastatic pretreated thymic epithelial tumors (TETs). Ann Oncol. 2010 Jun;21(6):1168-72. Epub 2009 Oct 30. link to original article EuroPMC
## Update: Palmieri G, Buonerba C, Ottaviano M, Federico P, Calabrese F, Von Arx C, De Maio AP, Marino M, Lalle M, Montella L, Merola C, Milella M, Bergaglio M, Di Lorenzo G, Damiano V. Capecitabine plus gemcitabine in thymic epithelial tumors: final analysis of a Phase II trial. Future Oncol. 2014 Nov;10(14):2141-7. link to original article dosing details in abstract have been reviewed by our editors EuroPMC
==Everolimus monotherapy==
===Regimen===
Study 	Dates of enrollment 	Evidence	Efficacy
Zucali et al. 2017 (ONC-2010-001)	2011-02-17 to 2013-10-21	Phase 2 	DCR: 88%
====Targeted therapy====
*Everolimus (Afinitor) 10 mg PO once per day
Continued indefinitely
===References===
# ONC-2010-001: Zucali PA, De Pas T, Palmieri G, Favaretto A, Chella A, Tiseo M, Caruso M, Simonelli M, Perrino M, De Vincenzo F, Toffalorio F, Damiano V, Pasello G, Garbella E, Ali M, Conforti F, Ottaviano M, Cioffi A, De Placido S, Giordano L, Bertossi M, Destro A, Di Tommaso L, Santoro A. Phase II study of everolimus in patients with thymoma and thymic carcinoma previously treated with cisplatin-based chemotherapy. J Clin Oncol. 2018 Feb 1;36(4):342-349. Epub 2017 Dec 14. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
==Ifosfamide monotherapy==
===Regimen variant #1, intermittent dosing===
Study 	Dates of enrollment	Evidence
Highley et al. 1999	1984-07 to 1996-07 	Pilot, fewer than 20 pts
====Chemotherapy====
*Ifosfamide (Ifex) 1500 mg/m2 IV over 30 minutes once per day on days 1 to 5
====Supportive therapy====
*Mesna (Mesnex) 400 mg IV bolus once per day on days 1 to 5, given before ifosfamide, then 1000 mg/m2 IV over 7.5 hours (total dose per cycle: 7000 mg/m2)
21-day cycles
===Regimen variant #2, continuous dosing===
Study 	Dates of enrollment	Evidence
Highley et al. 1999	1984-07 to 1996-07 	Pilot, fewer than 20 pts
====Chemotherapy====
*Ifosfamide (Ifex) 1500 mg/m2/day IV continuous infusion over 120 hours, started on day 1, given second (total dose per cycle: 6000 mg/m2)
====Supportive therapy====
*Mesna (Mesnex) 2000 mg IV bolus once on day 1, given first, then 1500 mg/m2/day IV continuous infusion over 7 days (total dose per cycle: 12,500 mg/m2)
21-day cycles
===References===
# Highley MS, Underhill CR, Parnis FX, Karapetis C, Rankin E, Dussek J, Bryant B, Rowland C, Hodson N, Hughes J, Harper PG. Treatment of invasive thymoma with single-agent ifosfamide. J Clin Oncol. 1999 Sep;17(9):2737-44. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC content property of HemOnc.org
==Octreotide monotherapy==
===Regimen variant #1, brief course===
Study 	Dates of enrollment	Evidence
Loehrer et al. 2004	1998-04 to 2000-11 	Phase 2
====Endocrine therapy====
*Octreotide (Sandostatin) 0.5 mg SC three times per day
1-month cycle for 2 cycles
====Subsequent treatment====
*Loehrer et al. 2004, stable disease: octreotide & prednisone
===Regimen variant #2, extended course===
Study 	Dates of enrollment	Evidence
Loehrer et al. 2004	1998-04 to 2000-11 	Phase 2
====Endocrine therapy====
*Octreotide (Sandostatin) 0.5 mg SC three times per day
1-month cycle for up to 12 cycles
===References===
# Loehrer PJ Sr, Wang W, Johnson DH, Aisner SC, Ettinger DS; Eastern Cooperative Oncology Group. Octreotide alone or with prednisone in patients with advanced thymoma and thymic carcinoma: an Eastern Cooperative Oncology Group Phase II Trial. J Clin Oncol. 2004 Jan 15;22(2):293-9. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
==Octreotide & Prednisone==
===Regimen===
Study 	Dates of enrollment	Evidence
Loehrer et al. 2004	1998-04 to 2000-11 	Phase 2
====Preceding treatment====
*Octreotide x 2 mo
====Endocrine therapy====
*Octreotide (Sandostatin) 0.5 mg SC three times per day
*Prednisone (Sterapred) 0.6 mg/kg PO once per day
1-month cycle for up to 10 cycles
===References===
# Loehrer PJ Sr, Wang W, Johnson DH, Aisner SC, Ettinger DS; Eastern Cooperative Oncology Group. Octreotide alone or with prednisone in patients with advanced thymoma and thymic carcinoma: an Eastern Cooperative Oncology Group Phase II Trial. J Clin Oncol. 2004 Jan 15;22(2):293-9. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
==Sunitinib monotherapy==
===Regimen===
Study 	Dates of enrollment 	Evidence
Thomas et al. 2015 (NCI 12-C-0118)	2012-05-15 to 2013-10-02	Phase 2
====Targeted therapy====
*Sunitinib (Sutent) 50 mg PO once per day on days 1 to 28
42-day cycles
===References===
# NCI 12-C-0118: Thomas A, Rajan A, Berman A, Tomita Y, Brzezniak C, Lee MJ, Lee S, Ling A, Spittler AJ, Carter CA, Guha U, Wang Y, Szabo E, Meltzer P, Steinberg SM, Trepel JB, Loehrer PJ, Giaccone G. Sunitinib in patients with chemotherapy-refractory thymoma and thymic carcinoma: an open-label phase 2 trial. Lancet Oncol. 2015 Feb;16(2):177-86. Epub 2015 Jan 13. Erratum in: Lancet Oncol. 2015 Mar;16(3):e105. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article EuroPMC NCT01621568
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