Thymoma

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First-line therapy

ADOC

ADOC: Adriamycin, cis-Diamminedichloroplatinum, Oncovin, Cyclophosphamide

Regimen

Level of Evidence: 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.

• Doxorubicin (Adriamycin) 40 mg/m2 IV on day 1
• Cisplatin (Platinol) 50 mg/m2 IV on day 1
• Vincristine (Oncovin) 0.6 mg/m2 IV on day 3
• Cyclophosphamide (Cytoxan) 700 mg/m2 IV on day 4

21 to 28-day cycles--see note above regarding duration of cycles

References

1. 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

Regimen

Level of Evidence: Phase II

• Carboplatin (Paraplatin) AUC 6 IV over 30 minutes on day 1, given second
• Paclitaxel (Taxol) 225 mg/m2 IV over 3 hours on day 1, given first

21-day cycles x up to 6 cycles

Supportive medications:

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

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

PAC: Platinol, Adriamycin, Cyclophosphamide
CAP: Cyclophosphamide, Adriamycin, Platinol

Regimen

Level of Evidence: Phase II

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

21-day cycles x up to 8 cycles

Supportive medications:

• 1 liter normal saline 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

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
2. 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 (Sterapred), surgery, RT, chemo

PAC: Platinol, Adriamycin, Cyclophosphamide

Regimen

Level of Evidence: 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 phase:

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

21 to 28-day cycles x 3 cycles

Supportive medications:

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

• Surgical resection is performed if CT scan 3-4 weeks after the third cycle of chemotherapy shows disease amenable resection
• If tumor is completely resected and has at least 80% necrosis, 50 Gy radiation therapy is administered 3-6 weeks after surgery
  • If tumor is incompletely resected or has <80% necrosis, 60 Gy radiation therapy is administered

Consolidation phase (at 80% of the induction doses of cisplatin, doxorubicin, and cyclophosphamide; 100% dose of prednisone):

• Cisplatin (Platinol) 24 mg/m2 IV once per day on days 1 to 3
• Doxorubicin (Adriamycin) 16 mg/m2/day (48 mg/m2 total dose) IV continuous infusion once per day on days 1 to 3
• Cyclophosphamide (Cytoxan) 400 mg/m2 IV by slow injection or infusion on day 1
• Prednisone (Sterapred) 100 mg PO once per day on days 1 to 5

21 to 28-day cycles x 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

PE: Platinol, Etoposide

Regimen

Level of Evidence: Phase II

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

21-day cycles x up to 8 cycles

Supportive medications:

• "A program of forced hydration"

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

VIP: Vepesid, Ifosfamide, Platinol

Regimen

Level of Evidence: Phase II

• 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
• Mesna (Mesnex) 240 mg/m2 IV push before, 4 hours after, and 8 hours after ifosfamide once per day on days 1 to 4
• Cisplatin (Platinol) 20 mg/m2 IV once per day on days 1 to 4

21-day cycles x 4 cycles

Supportive medications:

• 1 liter normal saline prior to cisplatin
• Filgrastim (Neupogen) 5 mcg/kg SC once per day on days 5 to 15, until WBC at least 10,000 postnadir

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

Ifosfamide (Ifex)

Regimen #1, Highley, et al. 1999

Level of Evidence: Pilot, <20 patients reported

• Ifosfamide (Ifex) 1500 mg/m2 IV over 30 minutes once per day on days 1 to 5
• Mesna (Mesnex) 400 mg IV bolus before ifosfamide, then Mesna (Mesnex) 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, Highley, et al. 1999

Level of Evidence: Pilot, <20 patients reported

• Mesna (Mesnex) 2000 mg IV bolus on day 1, given first
• A 3 liter solution of D5NS containing the following is then given IV continuous 24-hour infusion once per day on days 1 to 5
  • Ifosfamide (Ifex) 1500 mg/m2/day IV continuous 24-hour infusion once per day on days 1 to 5
  • Mesna (Mesnex) 1500 mg/m2/day IV continuous 24-hour infusion once per day on days 1 to 5
• Mesna (Mesnex) 1500 mg/m2/day in 3 liters of D5NS IV continuous 24-hour infusion once per day on days 6 to 8

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)

Regimen

Level of Evidence: Randomized Phase II, >20 per arm

• Octreotide (Sandostatin) 0.5 mg SC TID

1-month cycles x 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 (Sandostatin) & Prednisone (Sterapred)

Regimen

Level of Evidence: Randomized Phase II, >20 per arm

• Octreotide (Sandostatin) 0.5 mg SC TID

1-month cycles x 2 cycles

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

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

1-month cycles x 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