COMBINED SYSTEMIC CHEMOIMMUNOTHERAPY IN ADVANCED DIFFUSE MALIGNANT MESOTHELIOMA - REPORT OF A PHASE I-II STUDY OF WEEKLY CISPLATIN INTERFERON ALFA-2A

Purpose: To assess the tolerance, toxicity, and antitumoral activity o f the weekly combination of cisplatin (CDDP) and interferon alfa-2a (I FN alpha 2a) in advanced diffuse malignant mesothelioma (DMM). Patient s and Methods: Twenty-six patients with DMM (23 pleural and three peri toneal), previously untreated, were enrolled onto this study between A ugust 1991 and December 1992. All patients had measurable disease defi ned by computed tomographic (CT) scan and diagnostic confirmation by h istopathology review panel. lFN alpha 2a (3 x 10(6) IU subcutaneously On days 1 to 4) and CDDP (60 mg/m(2)/wk on day 2) were given weekly. i nitially planned as a 5-weeks-on/3-weeks-off treatment cycle, poor pat ient tolerance observed in the first 12 patients treated (group A) led to schedule adaptation with a shorter treatment sequence and prolonga tion of the rest period (4 weeks on/4 weeks off) in the following 14 p atients (group 8). At least two cycles were administered to each patie nt in the absence of tumor progression. Results: Twenty-six patients w ere assessable for toxicity and 25 for efficacy (World Health Organiza tion [WHO] criteria). Sixty-eight cycles of IFN/CDDP were given, with a median of three cycles per patient (range, one to five). Toxicity wa s mainly clinical, with progressive anorexia, asthenia, and prolonged nausea/emesis; these side effects have limited treatment acceptance in many patients. Thrombocytopenia and leukopenia were rarely noted as t reatment-limiting toxicities. Objective responses (all partial) were o btained in 10 patients (95% confidence interval [CI], 20% to 60%). The median response duration was 11 months (range, 6 to 18). The median t ime to progression (TTP) for the whole cohort was 6 months and the med ian survival time was 12 months (range, 5 to 32). Objective responders had a significantly longer median TTP (21 months) and survival time ( 25 months) than nonresponders (3 and 8 months, respectively). Conclusi on: The results of this pilot phase I-II study show encouraging antitu mor activity in this traditionally resistant tumor, even if the specif ic contribution of IFN remains speculative and needs further clinical research. Our ongoing program is exploring the dose-intensity impact o f IFN dose within the same combination. (C) 1996 by American Society o f Clinical Oncology.