Chemotherapy for Advanced Thymoma

Abstract

Objective: To determine the efficacy of combination therapy with cisplatin, doxorubicin, and cyclophosphamide alone or with radiotherapy for patients with extensive and those with limited unresectable thymoma.

Design: Nonrandomized, prospective phase I-II trial.

Setting: A Cooperative Oncology Group trial involving tertiary medical centers.

Patients: Twenty of twenty-two patients with measurable, extensive or limited, unresectable thymoma were evaluable for response.

Intervention: Patients were given cisplatin, 50 mg/m² body surface area, doxorubicin, 50 mg/m, and cyclophosphamide, 500 mg/m², on day 1, with cycles repeated every 21 days until progression or until the maximally tolerated total doxorubicin dosage (for example, 450 mg/m²) was reached. Intravenous hydration with normal saline was administered during treatment courses. For responding patients with limited disease, 4500 cGy was administered to primary tumors after the second cycle of chemotherapy and before the initiation of the third cycle.

Measurements and Main Results: Three complete and eleven partial remissions were seen in 20 evaluable patients, for a total response rate of 70% (95% CI, 46% to 88%). The median duration of remission was 13 months with three patients remaining continuously disease free for over 2 years. The median survival time of all eligible patients was 59 months (CI, 22 months to infinity). Four patients developed infections, including listerial and aseptic meningitides, mucocutaneous candidiasis, and cryptococcal pneumonia, that were indicative of a defect in cell-mediated immunity.

Conclusions: Combination therapy with cisplatin, doxorubicin, and cyclophosphamide frequently produces objective remissions in patients with advanced thymoma. Further experience with this treatment regimen is warranted to clarify potential prognostic factors in patients with unresectable thymoma.