DIHYDRO-5-AZACYTIDINE AND CISPLATIN IN THE TREATMENT OF MALIGNANT MESOTHELIOMA - A PHASE-II STUDY BY THE CANCER AND LEUKEMIA GROUP-B

BACKGROUND, In a prior Cancer and Leukemia Group B (CALGB) Phase II tr ial of patients with advanced, previously untreated mesothelioma, dihy dro-5-azacytidine (DHAC) demonstrated a 17% response rate, including 1 complete response, with only mild myelosuppression. This Phase II stu dy (CALGB 9031) was conducted to determine the effectiveness of and to xicities that would result from adding cisplatin to DHAC administered to the same patient population. METHODS, Thirty-six patients were trea ted with concurrent DHAC at 1500 mg/m(2)/day for 5 days by continuous infusion and cisplatin 15 mg/m(2) daily for 5 days. Therapy was repeat ed every 3 weeks. Cisplatin was to be increased to 20 mg/m(2) daily in subsequent cycles if toxicity was minimal. Therapy was continued unti l disease progression or excessive toxicity mandated discontinuation. RESULTS, Overall, 5 objective responses were observed in 29 evaluated patients (objective response rate, 17%). The median duration of respon se was 6.6 months. Median survival was 6.4 months, with a median time to clinical failure of 2.7 months. The major toxicity noted was signif icant chest/pericardial pain, as was observed with DHAC alone. There w ere 2 early deaths of unknown cause on Days 9 and 17 of therapy, respe ctively. Significant leukopenia was observed in 29% of patients, but t here were no neutropenic fevers. CONCLUSIONS. The addition of cisplati n to DHAC did not increase the response rate over that observed with D HAC alone in patients with mesothelioma; however, it did increase toxi city, especially leukopenia. This combination is not recommended for f urther studies involving mesothelioma patients. (C) 1998 American Canc er Society.