Gemcitabine combined with carboplatin in patients with malignant pleural mesothelioma

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Abstract
BACKGROUND Malignant pleural mesothelioma (MPM) is increasing rapidly worldwide. Currently, pemetrexed plus cisplatin chemotherapy showed a survival advantage versus cisplatin alone. No impact on patient survival of surgery, radiotherapy, or their combination has been demonstrated. METHODS Eight centers in northeastern Italy participated in a Phase II multicenter study. Chemotherapy was comprised of carboplatin area under the concentration‐time curve 5 on Day 1 and gemcitabine 1000 mg/m2 on Days 1, 8, and 15. This cycle was repeated every 4 weeks. RESULTS Between July 1996 and September 2000, 50 patients were treated. Of the sample, 68% were males, 88% had a Eastern Cooperative Oncology Group performance status score of 0–1, 56% had Stage I–II disease, 68% had epithelioid histology, and 62% had no previous treatments. The delivered dose intensity of gemcitabine was 617 mg/m2 per week, which was 82% of the planned dose (750 mg/m2 per week). For carboplatin, the delivered dose intensity was 80 mg/m2 per week. Overall, 44% of 15th day doses were omitted or reduced. Twenty‐six percent of the patients had partial responses (95% confidence interval: 15–40%) and 24% had disease progression. None of the patients had complete responses. The median response duration was 55 weeks (range, 13–113 weeks). Patients had good clinical benefit. For example, 46% had improved dyspnea, 40% improved in weight, and 26% experienced pain reduction. Patients developed Grade 3–4 leukopenia during 18 cycles (11%) of chemotherapy. Grade 3–4 thrombocytopenia occurred more frequently, i.e., there were 24 episodes (15%) among 17 patients. Grade 3 anemia developed among patients during eight cycles (5%). None of the patients developed Grade 3–4 nonhematologic toxicity. The median survival of this sample of patients was 66 weeks with 53%, 30%, and 20% of patients alive at 1, 2, and 3 years, respectively. The median progression‐free survival period was 40 weeks. CONCLUSIONS The gemcitabine/carboplatin combination is a valid option in the treatment of MPM due to its acceptable toxicity profile, the good response rate, and the clinical benefit to patients. Minor adjustments in schedule (3‐week cycles instead of 4‐week cycles) would permit a more optimal treatment administration. Cancer 2003;97:2791–7. © 2003 American Cancer Society. DOI 10.1002/cncr.11405