Thymoma

Section editor
	Amit Kulkarni, MBBS University of Minnesota Minneapolis, MN, USA LinkedIn

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 PubMed

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

1. 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 PubMed

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

1. 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 PubMed

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

1. 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 PubMed

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

1. 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 PubMed

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

1. 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 PubMed

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	Not reported in abstract	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

1. 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 PubMed
   1. 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 PubMed

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

1. 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 PubMed

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

1. 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 PubMed

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

1. 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 PubMed
   1. 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 PubMed

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

1. 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 PubMed

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

1. 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 PubMed 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

1. 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 PubMed

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

1. 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 PubMed

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

1. 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 PubMed NCT01621568