Thymoma Treatment Protocols 

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Treatment protocols for thymoma are provided below, including the following ^{[1, 2, 3]} :

Treatment recommendations are as follows:

Stage I: Complete surgical excision is the treatment of choice for nonmetastatic thymoma and thymic carcinoma, even when the tumor is locally advanced

Stages II-III: Complete surgical excision and postoperative radiotherapy is recommended to decrease the incidence of local recurrence

Stages IVA and IVB: Surgical debulking, radiotherapy, and chemotherapy are recommended

A number of studies have demonstrated that certain chemotherapy drugs can induce tumor responses either as single agents or in combination. In general, higher response rates have been reported with combinations; however, no randomized trials have been conducted to date. Because of the rarity of thymomas, the published experience with chemotherapy is mostly limited to case reports, retrospective reviews, and small prospective trials. ^{[4, 5, 6]}

First-line chemotherapy

Regimens are as follows:

Preferred for thymoma ^[7] : Cisplatin + doxorubicin (Adriamycin) + cyclophosphamide (CAP): Cisplatin 50 mg/m² IV plus  doxorubicin 50 mg/m² IV push plus  cyclophosphamide 500 mg/m²; every 3 wk for two to to four cycles ^[8] or

Cisplatin + doxorubicin + cyclophosphamide + prednisone (CAPP): Cisplatin 30 mg/m² IV on days 1-3 plus  doxorubicin 20 mg/m²/day continuous IV infusion on days 1-3 plus  cyclophosphamide 500 mg/m² IV on day 1 plus  prednisone 0.6 mg/kg/day PO (typically ~100 mg/day) on days 1-5; every 3 wk for up to eight cycles ^[9] or

Cyclophosphamide + doxorubicin + vincristine (CAV): Cyclophosphamide 800 mg/m² plus  doxorubicin 50 mg/m² plus  vincristine 1.4 mg/m²; every 3 wk for two to to four cycles or

Doxorubicin + cisplatin + vincristine + cyclophosphamide (ADOC): Doxorubicin 40 mg/m² IVP on day 1 plus  cisplatin 50 mg/m² on day 1 plus  vincristine 0.6 mg/m² IV (not to exceed 2 mg/dose) on day 3 plus  cyclophosphamide 700 mg/m² on day 4; every 3 wk for up to eight cycles ^[5] or

Cisplatin + etoposide (PE): Cisplatin 60 mg/m² IV on day 1 plus  etoposide 120 mg/m² IV on days 1 to 3; every 3 wk for up to eight cycles ^[10] or

Etoposide (VisPesid + ifosfamide + cisplatin (VIP): Cisplatin 20 mg/m² IV on days 1-4 plus  etoposide 75 mg/m² IV on days 1-4 plus  ifosfamide 1.2 g/m² IV on days 1-4; every 3 wk for up to eight cycles (Note: give mesna 240 mg/m² IV over 15 min immediately before ifosfamide) ^[11] or

Preferred for thymic carcinoma –  Carboplatin + paclitaxel: Carboplatin AUC 6 (see the Carboplatin AUC Dose Calculation [Calvert formula]plus  paclitaxel 200 mg/m² IV on day 1; every 3 wk for six cycles ^[12]

Second-line chemotherapy

Second-line chemotherapeutic agents that may be used when first-line treatment fails may include the drugs listed below. Dosing is individualized and should be recommended by a specialist. ^[7] Regimens are as follows:

Sunitinib (thymic carcinomas only) 50 mg PO on days 1-28 of 6-wk cycle ^{[7, 13]}

Everolimus 10 mg PO daily ^[7]

Etoposide 120 mg/m² IV on days 1-3 every 21 d or 50 mg/m² PO daily on days 1-21 every 28-35 d

Ifosfamide 1500 mg/m² IV on days 1-5 every 21 d plus predose mesna

Pemetrexed 500 mg/m² IV on day 1; every 21 d for six cycles

Octreotide 500 mcg SC TID on days 1-28 +/- prednisone 0.6 mg/kg PO daily on days 1-28; 28 d cycle for up to 12 cycles

5-Fluorouracil (5-FU) 400 mg/m² IV on day 1 (preceded by leucovorin 400 mg/m² IV) plus  5-FU 1200 mg/m²/day continuous IV infusion on days 1 and 2

Gemcitabine 1000 mg/m² IV on days 1, 8, and 15; every 28 d

Paclitaxel 80 mg/m² IV on days 1 and 8; every 21 d

Thymomas may  recur after several years; therefore, long-term follow-up and monitoring are recommended. For patients with metastatic disease, chemotherapy is the primary treatment for unresectable or metastatic thymoma or thymic carcinoma. Regimens include agents such as cisplatin and ifosfamide. Studies have demonstrated that combination chemotherapy produces higher response rates.

Combination therapies for metastatic disease include the following:

Cisplatin 50 mg/m² plus  doxorubicin 50 mg/m² plus  cyclophosphamide 500 mg/m² on day 1 ^[8] or

Cisplatin 50 mg/m² on day 1 plus  doxorubicin 40 mg/m² on day 1 plus  cyclophosphamide 700 mg/m² on day 4 plus  vincristine 0.6 mg/m² on day 3 ^[10] or

Etoposide 120 mg/m² on days 1 and 3 plus  cisplatin 60 mg/m² on day 1;  every 21 d ^[14]

Additional regimens that have been studied include carboplatin and paclitaxel, as well as pemetrexed and irinotecan with cisplatin or carboplatin

Features of radiation therapy are as follows:

Adjuvant radiation therapy ^[15] for completely or incompletely resected stage III or IV thymomas is considered a standard of care

Recommended doses include 45-50 Gy for clear/close margins; 54 Gy for microscopically positive margins; 60 Gy or more for gross residual disease

Use of postoperative radiation therapy for stage II thymomas has been more questionable

For palliative treatment, the recommended radiation dose is 60-70 Gy for unresectable disease

In a report from Massachusetts General Hospital, 22% of patients (5 out of 23) with stage II disease developed recurrence, leading to a proposed recommendation that postoperative radiation therapy be instituted in all patients with stage II thymoma ^[16]

To reduce the incidence of local relapse, administer postoperative adjuvant radiation therapy to patients with stage I tumors that are not completely encapsulated ^[1]

Wu et al performed a retrospective review of 241 patients with thymoma who received radiation therapy after total thymectomy, partial resection, debulking, or biopsy; the 10-y survival rate was 87% with stage I thymoma, 78.7% with stage II, 57.4% with stage III, and 24.3% with stage IV; the authors concluded that surgery and postoperative radiation treatment should be standard care measures for patients with stage II or III thymoma ^[17]

Venuta F, Anile M, Diso D, Vitolo D, Rendina EA, De Giacomo T, et al. Thymoma and thymic carcinoma. Eur J Cardiothorac Surg. 2010 Jan. 37(1):13-25. [Medline].

Wright CD. Pleuropneumonectomy for the treatment of Masaoka stage IVA thymoma. Ann Thorac Surg. 2006 Oct. 82(4):1234-9. [Medline].

Giaccone G, Kelly, K. Treatment of thymoma: a comparative study between Thailand and the United States and a review of the literature. Am J Clin Oncol. 2004;27: 236-46.

Sunpaweravong P, Kelly K. Treatment of thymoma: a comparative study between Thailand and the United States and a review of the literature. Am J Clin Oncol. 2004 Jun. 27(3):236-46. [Medline].

Fornasiero A, Daniele O, Ghiotto C, Piazza M, Fiore-Donati L, Calabró F, et al. Chemotherapy for invasive thymoma. A 13-year experience. Cancer. 1991 Jul 1. 68(1):30-3. [Medline].

Barratt S, Puthucheary ZA, Plummeridge M. Complete regression of a thymoma to glucocorticoids, commenced for palliation of symptoms. Eur J Cardiothorac Surg. 2007 Jun. 31(6):1142-3. [Medline].

NCCN Clinical Practice Guidelines in Oncology: Thymoma and Thymic Carcinoma. National Comprehensive Cancer Network. Available at http://www.nccn.org/professionals/physician_gls/pdf/thymic.pdf. Version 2.2018 — February 16, 2018; Accessed: April 4, 2018.

Loehrer PJ Sr, Kim K, Aisner SC, Livingston R, Einhorn LH, Johnson D, et al. 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. [Medline].

Kim ES, Putnam JB, Komaki R, Walsh GL, Ro JY, Shin HJ, et al. 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. [Medline].

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. [Medline].

Loehrer PJ Sr, Jiroutek M, Aisner S, Aisner J, Green M, Thomas CR Jr, et al. 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. [Medline].

Lemma GL, Lee JW, Aisner SC, Langer CJ, Tester WJ, Johnson DH, et al. Phase II study of carboplatin and paclitaxel in advanced thymoma and thymic carcinoma. J Clin Oncol. 2011 May 20. 29(15):2060-5. [Medline]. [Full Text].

Thomas A, Rajan A, Berman A, Tomita Y, Brzezniak C, Lee MJ, et al. Sunitinib in patients with chemotherapy-refractory thymoma and thymic carcinoma: an open-label phase 2 trial. Lancet Oncol. 2015 Feb. 16 (2):177-86. [Medline].

Kanda S, Koizumi T, Komatsu Y, Yoshikawa S, Okada M, Hatayama O, et al. Second-line chemotherapy of platinum compound plus CPT-11 following ADOC chemotherapy in advanced thymic carcinoma: analysis of seven cases. Anticancer Res. 2007 Jul-Aug. 27(4C):3005-8. [Medline].

Fernandes AT, Shinohara ET, Guo M, Mitra N, Wilson LD, Rengan R, et al. The role of radiation therapy in malignant thymoma: a Surveillance, Epidemiology, and End Results database analysis. J Thorac Oncol. 2010 Sep. 5(9):1454-60. [Medline].

Wilkins EW Jr, Grillo HC, Scannell JG, Moncure AC, Mathisen DJ. J. Maxwell Chamberlain Memorial Paper. Role of staging in prognosis and management of thymoma. Ann Thorac Surg. 1991 Jun. 51(6):888-92. [Medline].

Wu KL, Mao JF, Chen GY, Fu XL, Qian H, Jiang GL. Prognostic predictors and long-term outcome of postoperative irradiation in thymoma: a study of 241 patients. Cancer Invest. 2009 Jun 22. 1. [Medline].

Quintessa Miller, MD 

Quintessa Miller, MD is a member of the following medical societies: American College of Surgeons, National Medical Association

Disclosure: Nothing to disclose.

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

Christopher D Braden, DO Hematologist/Oncologist, Chancellor Center for Oncology at Deaconess Hospital; Medical Director, Deaconess Hospital Outpatient Infusion Centers; Chairman, Deaconess Hospital Cancer Committee

Christopher D Braden, DO is a member of the following medical societies: American Society of Clinical Oncology, American Society of Hematology

Disclosure: Nothing to disclose.

Neetu Radhakrishnan, MD Associate Professor (Adjunct) of Medicine, Division of Hematology/Oncology, University of Cincinnati Medical Center; Hematology/Oncology Medical Director, West Chester Outpatient Clinics

Neetu Radhakrishnan, MD is a member of the following medical societies: American College of Physicians, American Society of Clinical Oncology, American Society of Hematology

Disclosure: Nothing to disclose.

Thymoma Treatment Protocols 

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