HIGHER DOSES OF ALPHA-INTERFERON DO NOT INCREASE THE ACTIVITY OF THE WEEKLY CISPLATIN-INTERFERON COMBINATION IN ADVANCED MALIGNANT MESOTHELIOMA

Management of advanced malignant mesothelioma (MM) still requires inno vative systemic therapy as its prognosis is poorly affected by current ly available chemotherapy. The combination cisplatin and alpha-interfe ron (alpha-IFN) has synergistic antitumoral activity in preclinical mo dels and interesting activity in phase I-II clinical trials. Weekly CD DP (60 mg/m(2)) and alpha-IFN (3 MUI/d: d1-d4) in combination was test ed in a previous phase I-II study in 23 MM patients, with a 36% object ive response rate (ORR). A trial with higher doses of alpha-IFN in the same combination schedule was conducted to explore an incrementalist hypothesis. Thirty patients with MM received the same CDDP dose (60 mg /m(2)/w) and doubled doses of alpha-IFN (6 MUI/d: d1-d4). The treatmen t protocol consisted of two cycles of 4 weeks on/4 weeks off followed by two shorter cycles of 3 weeks on/3 weeks off, in the absence of lif e-threatening toxicity or progressive disease. All patients were evalu able for toxicity. The main treatment-limiting side-effects were diges tive intolerance (nausea, vomiting) and severe asthenia. Antitumoral e fficacy was not increased (ORR=27%). Haematological and neurological t oxicities were moderate and manageable. The antitumoral activity of th e CDDP-alpha-IFN combination with higher doses of the latter is simila r to our previous experience, but tolerance issues make it a poorer ch oice for eventual comparative trials, or as a standard therapeutic ind ication. (C) 1997 Published by Elsevier Science Ltd.