Thymoma Treatment Protocols 

Updated: Jul 07, 2015
  • Author: Quintessa Miller, MD; Chief Editor: Jules E Harris, MD, FACP, FRCPC  more...
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Treatment Protocols

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

  • Treatment by Masaoka clinical stage
  • Chemotherapy regimens
  • Recommendations for recurrent or metastatic disease
  • Radiotherapy regimens

Treatment recommendations based on Masaoka clinical stage

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

Chemotherapeutic regimens

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/m 2 IV plus  doxorubicin 50 mg/m 2 IV push plus  cyclophosphamide 500 mg/m 2; every 3 wk for two to to four cycles [8] or
  • Cisplatin + doxorubicin + cyclophosphamide + prednisone (CAPP): Cisplatin 30 mg/m 2 IV on days 1-3 plus  doxorubicin 20 mg/m 2/day continuous IV infusion on days 1-3 plus  cyclophosphamide 500 mg/m 2 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/m 2 plus  doxorubicin 50 mg/m 2 plus  vincristine 1.4 mg/m 2; every 3 wk for two to to four cycles or
  • Doxorubicin + cisplatin + vincristine + cyclophosphamide (ADOC): Doxorubicin 40 mg/m 2 IVP on day 1 plus  cisplatin 50 mg/m 2 on day 1 plus  vincristine 0.6 mg/m 2 IV (not to exceed 2 mg/dose) on day 3 plus  cyclophosphamide 700 mg/m 2 on day 4; every 3 wk for up to eight cycles [5] or
  • Cyclophosphamide + doxorubicin + vincristine + prednisone (CHOP): Cyclophosphamide 500 mg/m 2 plus  doxorubicin 50 mg/m 2 plus  vincristine 1.4 mg/m 2 plus  prednisone 0.6 mg/kg/day; every 3 wk for two to to four cycles or
  • Cisplatin + doxorubicin + cyclophosphamide + etoposide (PACE): Cisplatin 80 mg/m 2 IV plus  doxorubicin 45 mg/m 2 plus  cyclophosphamide 800 mg/m 2 IV on day 1 plus  etoposide 80 mg/m 2 IV on days 1-3 or
  • Cisplatin + etoposide (PE): Cisplatin 60 mg/m 2 IV on day 1 plus  etoposide 120 mg/m 2 IV on days 1 to 3; every 3 wk for up to eight cycles [10] or
  • Etoposide (VisPesid + ifosfamide + cisplatin (VIP): Cisplatin 20 mg/m 2 IV on days 1-4 plus  etoposide 75 mg/m 2 IV on days 1-4 plus  ifosfamide 1.2 g/m 2 IV on days 1-4; every 3 wk for up to eight cycles (Note: give mesna 240 mg/m 2 IV over 15 min immediately before ifosfamide) [11] or
  • Preferred for thymic carcinoma -  Carboplatin + paclitaxel: Carboplatin AUC 6 plus  paclitaxel 225 mg/m 2 IV on day 1; every 3 wk for six cycles (see the Carboplatin AUC Dose Calculation [Calvert formula] calculator) [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/m 2 IV on days 1-3 every 21 d or 50 mg/m 2 PO daily on days 1-21 every 28-35 d
  • Ifosfamide 1500 mg/m 2 IV on days 1-5 every 21 d plus predose mesna
  • Pemetrexed 500 mg/m 2 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/m 2 IV on day 1 (preceded by leucovorin 400 mg/m 2 IV) plus  5-FU 1200 mg/m 2/day continuous IV infusion on days 1 and 2
  • Gemcitabine 1000 mg/m 2 IV on days 1, 8, and 15; every 28 d
  • Paclitaxel 80 mg/m 2 IV on days 1 and 8; every 21 d

Recurrent or metastatic disease

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/m 2 plus  doxorubicin 50 mg/m 2 plus  cyclophosphamide 500 mg/m 2 on day 1 [8] or
  • Cisplatin 50 mg/m 2 on day 1 plus  doxorubicin 40 mg/m 2 on day 1 plus  cyclophosphamide 700 mg/m 2 on day 4 plus  vincristine 0.6 mg/m 2 on day 3 [10] or
  • Etoposide 120 mg/m 2 on days 1 and 3 plus  cisplatin 60 mg/m 2 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

Radiation therapy

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]