Phase II Study OF Paclitaxel (TAXOL) and Cisplatin (CDDP) in Advanced Pleural Malignant Mesothelioma (MM)
R. Calinadro, C. Boutin, M. Perol, I. Monnet, G. Dabouis, J.C. Guerin, T. Le Chevalier, P. Ruffie.
Institut Gustave Roussy, Villejuif, Hopital de la Conception, marseille, Hopital de la Criox Rousse, Lyon, Centre Hospitalier Intercommunal de Creteil, Centre Hospitalier Univrsitaire de nantes, France.
MM is a rate chemoresistant tumor and chemotherapy (CT) remains controversial in it management. CDDP and Taxol have shown low antitumor activity in clinical trials, but are synergistic in experimental MM models. A french multicenter phase II study was initiated with the recommended doses from lung cancer studies: paclitaxel 200 mg/m2 I.V. over 3 hours D1, CDDP 100 mg/m2 I.V. D1, q 3 weeks with a maximum of 6 cycles. Responses were evaluated every 6 weeks. Between 11/95 and 05/96, 18 untreated patients (pts) were included.
Patients characteristics were: male/female 15/3, median age : 58 (35-70), WHO PS < 1, I.M.I.G. stages: Ib = 2, II = 5, III = 9, IV = 2, histologic subtype: epithelial: 15, biphasic = 1, desmoplastic = 2.
Results: 17 pts were evaluable for the response and toxicity analysis. Pts received a median of 3 cycles (1-6). Toxicity (WHO grad/pts): grade 3-4 nausea/vomiting: =5, grade 3-4 neutropenia =5, grad 3 anemia =1, grade 1-2 neurotoxicity =4, grade 2 renal toxicity =1. No toxic deaths. 1 objective partial response was observed (6%) with 11 stabilisations and 5 disease progressions. The median survival (MS) was 18 months from diagnostic. Median actuarial survival from the beginning of CT hasn't yet been reached to date.
Conclusion: Taxol - CDDP is an ineffective treatment in MM, and these results don't confirm in vivo promising data. MM persists to be a chemoresistant tumor and other therapeutic approaches will be considered.