Results of a Phase II trial of combined chemotherapy for patients with diffuse malignant mesothelioma of the pleura

BACKGROUND. Malignant pleural mesothelioma is associated with a poor prognosis because of its resistance to treatment. The authors conducted a Phase II trial in which two drugs (etoposide and 5-fluorouracil) were added to the Cancer and Leukemia Group B cisplatin-mitomycin regimen in an effort to define a more effective chemotherapy. METHODS, Forty-live patients with confirmed Stage II malignant pleural mesothelioma were prospectively enrolled in the study. Thirty-one patients received cisplatin 60 mg/m(2) on Day 1, 5-fluorouracil 600 mg on Days 1-4, folinic acid 100 mg/m(2) on Days 1-4, mitomycin C 10 mg/m(2) on Day 3, and etoposide 100 mg/m(2) i.v. on Days 1-3, with prophylactic hematopoietic growth factors. Fourteen patients received cisplatin, 5-fluorouracil, folinic acid, and mitomycin C with the protocol unchanged, and oral etoposide 50 mg on Days 1-21 without growth factors (1 cycle every 28 days). Histology included epithelial (in 33 cases), sarcomatous (in 6), mixed (in 3), and unspecified type (in 3). RESULTS. Two hundred eleven cycles were administered. Treatment was well tolerated and the major toxicity was hematologic: anemia in 30% of cases, neutropenia in 24%, and 2 probable cases of mitomycin-induced pneumonitis. The objective response rate was 38% (17 of 45 were partial responses), and the median response duration tvas 12 months. The median survival time was 16 months. There were no differences in response or survival between the 31 patients treated with growth factors and the 14 patients treated without them. Survival was slightly better for responders than for nonresponders who had stable disease or progression (20 vs. 10 months, P < 0.05). CONCLUSIONS. This four-drug combination was effective, with a notably high response rare, acceptable toxicity, and good adherence to protocol doses. The impact on survival was limited. (C) 1999 American Cancer Society.