Thymoma

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14 regimens on this page 16 variants on this page

Guidelines

ESMO

• Thymic epithelial tumours: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. (2015) PubMed

NCCN

• NCCN Guidelines - Thymomas and Thymic Carcinomas

First-line therapy

ADOC

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ADOC: Adriamycin (Doxorubicin), cis-Diamminedichloroplatinum (Cisplatin), Oncovin (Vincristine), Cyclophosphamide

Regimen

Study	Evidence
Fornasiero et al. 1991	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 the NCCN, Thymomas and Thymic Carcinomas version 2.2012, lists 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--see note above regarding duration of 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 contains verified protocol PubMed

Carboplatin & Paclitaxel

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Regimen

Study	Evidence
Lemma et al. 2011	Phase II

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 medications

• Cimetidine (Tagamet) 300 mg IV 1 hour prior to Paclitaxel (Taxol)
• Diphenhydramine (Benadryl) 25 mg IV 1 hour prior to Paclitaxel (Taxol)
• Dexamethasone (Decadron) 20 mg IV 1 hour prior to Paclitaxel (Taxol)

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 contains verified protocol PubMed

PAC; CAP

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PAC: Platinol (Cisplatin), Adriamycin (Doxorubicin), Cyclophosphamide
CAP: Cyclophosphamide, Adriamycin (Doxorubicin), Platinol (Cisplatin)

Regimen

Study	Evidence
Loehrer et al. 1990	Phase II

Chemotherapy

• Cisplatin (Platinol) 50 mg/m² IV over at least 1 hour once on day 1
• Doxorubicin (Adriamycin) 50 mg/m² IV by slow injection once on day 1
• Cyclophosphamide (Cytoxan) 500 mg/m² IV by slow injection or infusion once on day 1

Supportive medications

• 1 liter normal saline over 2 hours at least 2 hours before and after Cisplatin (Platinol) 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 contains verified protocol PubMed
   1. Update: Loehrer PJ Sr, Kim K, Aisner SC, Livingston R, Einhorn LH, Johnson D, Blum R. Cisplatin plus doxorubicin plus cyclophosphamide in metastatic or recurrent thymoma: final results of an intergroup trial. The Eastern Cooperative Oncology Group, Southwest Oncology Group, and Southeastern Cancer Study Group. J Clin Oncol. 1994 Jun;12(6):1164-8. link to original article contains verified protocol PubMed

PAC & Prednisone -> RT -> PAC & Prednisone

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PAC: Platinol, Adriamycin, Cyclophosphamide

Regimen

Study	Evidence
Kim et al. 2004	Phase II

Note: The NCCN, Thymomas and Thymic Carcinomas version 2.2012, lists only the induction phase of this regimen under its first-line options. No primary reference could be found for treatment with only the induction phase of therapy.

Induction chemotherapy

• Cisplatin (Platinol) 30 mg/m² IV once per day on days 1 to 3
• Doxorubicin (Adriamycin) 20 mg/m²/day IV continuous infusion on days 1 to 3 (total dose: 60 mg/m²)
• Cyclophosphamide (Cytoxan) 500 mg/m² IV by slow injection or infusion once on day 1
• Prednisone (Sterapred) 100 mg PO once per day on days 1 to 5

Supportive medications

• Metoclopramide (Reglan) 1 mg/kg IV prior to chemotherapy
• Diphenhydramine (Benadryl) 25 mg IV prior to chemotherapy

21 to 28-day cycle for 3 cycles

Surgical resection is performed if CT scan 3 to 4 weeks after the third cycle of chemotherapy shows disease amenable resection, and followed by:

Radiotherapy

• If tumor is completely resected and has at least 80% necrosis, 50 Gy radiation therapy is administered 3 to 6 weeks after surgery
• If tumor is incompletely resected or has less than 80% necrosis, 60 Gy radiation therapy is administered

One course, followed by consolidation:

Consolidation chemotherapy

• Cisplatin (Platinol) 24 mg/m² IV once per day on days 1 to 3
• Doxorubicin (Adriamycin) 16 mg/m²/day IV continuous infusion on days 1 to 3 (total dose: 48 mg/m²)
• Cyclophosphamide (Cytoxan) 400 mg/m² IV by slow injection or infusion once on day 1
• 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 contains verified protocol PubMed

PE

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PE: Platinol (Cisplatin), Etoposide

Regimen

Study	Evidence
Giaccone et al. 1996	Phase II

Chemotherapy

• Cisplatin (Platinol) 60 mg/m² IV over 1 hour once on day 1
• Etoposide (Vepesid) 120 mg/m² IV over at least 30 minutes once per day on days 1 to 3

Supportive medications

• "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. Cisplatin and etoposide combination chemotherapy for locally advanced or metastatic thymoma. A phase II study of the European Organization for Research and Treatment of Cancer Lung Cancer Cooperative Group. J Clin Oncol. 1996 Mar;14(3):814-20. link to original article contains verified protocol PubMed

VIP

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VIP: Vepesid (Etoposide), Ifosfamide, Platinol (Cisplatin)

Regimen

Study	Evidence
Loehrer et al. 2001	Phase II

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 medications

• Mesna (Mesnex) 240 mg/m² IV push before, 4 hours after, and 8 hours after Ifosfamide (Ifex) once per day on days 1 to 4
• 1 liter normal saline prior to Cisplatin (Platinol)
• Filgrastim (Neupogen) 5 mcg/kg SC once per day on days 5 to 15, until WBC at least 10,000 postnadir

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 contains verified protocol PubMed

Second-line therapy

Capecitabine & Gemcitabine

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CAP-GEM: CAPecitabine & GEMcitabine

Regimen

Study	Evidence
Palmieri et al. 2009	Phase II

Chemotherapy

• Capecitabine (Xeloda) 650 mg/m² PO BID 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 contains protocol PubMed

Everolimus (Afinitor)

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Regimen

Study	Evidence
Zucali et al. 2014	Phase II

Chemotherapy

• Everolimus (Afinitor) 10 mg PO once per day

Continued until progression or intolerance

References

1. Abstract: Paolo A. Zucali, Tommaso Martino De Pas, Giovannella Palmieri, Adolfo G. Favaretto, Antonio Chella, Marcello Tiseo, Michele Caruso, Matteo Perrino... Fabio De Vincenzo, Matteo Simonelli, Francesca Toffalorio, Piera Federico, Giulia Pasello, Marco Ali, Laura Giordano, Monica Bertossi, Armando Santoro. Phase II study of everolimus in patients with thymoma and thymic carcinoma previously treated with cisplatin-based chemotherapy. Journal of Clinical Oncology 32, no. 15_suppl (May 2014) 7527-7527. link to abstract

Ifosfamide (Ifex)

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Regimen #1

Study	Evidence
Highley et al. 1999	Pilot, <20 pts

Chemotherapy

• Ifosfamide (Ifex) 1500 mg/m² IV over 30 minutes once per day on days 1 to 5

Supportive medications

• Mesna (Mesnex) 400 mg IV bolus before ifosfamide, then 1000 mg/m² in 1 liter NS IV over 7.5 hours after ifosfamide once per day on days 1 to 5

21-day cycles

Regimen #2

Study	Evidence
Highley et al. 1999	Pilot, <20 pts

Chemotherapy

• • Ifosfamide (Ifex) 1500 mg/m²/day IV continuous infusion on days 1 to 5

Supportive medications

• Mesna (Mesnex) as follows:
  • Day 1: 2000 mg IV bolus on day 1, given first
  • Days 1 to 5: 1500 mg/m²/day in 3 liters of D5NS IV continuous infusion
  • Days 6 to 8: 1500 mg/m²/day in 3 liters of D5NS IV continuous infusion

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 contains verified protocol PubMed content property of HemOnc.org

Octreotide (Sandostatin)

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Regimen

Study	Evidence
Loehrer et al. 2004	Phase II

Endocrine therapy

• Octreotide (Sandostatin) 0.5 mg SC TID

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 Phase II Trial. 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 contains verified protocol PubMed

Octreotide & Prednisone

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Regimen

Study	Evidence
Loehrer et al. 2004	Phase II

Endocrine therapy, part 1

• Octreotide (Sandostatin) 0.5 mg SC TID

1-month cycle for 2 cycles

If stable disease after 2 cycles, patients would then receive:

Endocrine therapy, part 2

• Octreotide (Sandostatin) 0.5 mg SC TID
• Prednisone (Sterapred) 0.6 mg/kg PO once per day

1-month cycle for up to 10 additional cycles

References

1. Loehrer PJ Sr, Wang W, Johnson DH, Aisner SC, Ettinger DS; Eastern Cooperative Oncology Group Phase II Trial. 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 contains verified protocol PubMed

Sunitinib (Sutent)

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Regimen

Study	Evidence
Thomas et al. 2015	Phase II

Chemotherapy

• Sunitinib (Sutent) 50 mg PO once per day on days 1 to 28

42-day cycles, given until progression of disease or unacceptable toxicity

References

1. 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 PMC article contains verified protocol PubMed