Higher doses of alpha-interferon do not increase the activity of the weekly cisplatin-interferon combination in advanced malignant mesothelioma.

Journal Article (Clinical Trial;Journal Article)

Management of advanced malignant mesothelioma (MM) still requires innovative systemic therapy as its prognosis is poorly affected by currently available chemotherapy. The combination cisplatin and alpha-interferon (alpha-INF) has synergistic antitumoral activity in preclinical models and interesting activity in phase I-II clinical trials. Weekly CDDP (60 mg/m2) and alpha-IFN (3 MUI/d: d1-d4) in combination was tested in a previous phase I-II study in 23 MM patients, with a 36% objective 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/m2/w) and doubled doses of alpha-IFN (6 MUI/d: d1-d4). The treatment 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 life-threatening toxicity or progressive disease. All patients were evaluable for toxicity. The main treatment-limiting side-effects were digestive intolerance (nausea, vomiting) and severe asthenia. Antitumoral efficacy was not increased (ORR = 27%). Haematological and neurological toxicities were moderate and manageable. The antitumoral activity of the CDDP-alpha-IFN combination with higher doses of the latter is similar to our previous experience, but tolerance issues make it a poorer choice for eventual comparative trials, or as a standard therapeutic indication.

Full Text

Duke Authors

Cited Authors

  • Trandafir, L; Ruffié, P; Borel, C; Monnet, I; Soulié, P; Adams, D; Cvitkovic, E; Armand, JP

Published Date

  • October 1997

Published In

Volume / Issue

  • 33 / 11

Start / End Page

  • 1900 - 1902

PubMed ID

  • 9470855

International Standard Serial Number (ISSN)

  • 0959-8049

Digital Object Identifier (DOI)

  • 10.1016/s0959-8049(97)00263-3


  • eng

Conference Location

  • England