Combined regimen of cisplatin, doxorubicin, and alpha-2b interferon in thetreatment of advanced malignant pleural mesothelioma - A phase II multicenter trial of the Italian Group on Rare Tumors (GITR) and the Italian Lung Cancer Task Force (FONICAP)

BACKGROUND. The cisplatin-doxorubicin combination has shown moderate activi ty in malignant pleural mesothelioma (MPM; objective response, 25%), and pr eclinical studies suggest that interferons (IFNs) may have an antiprolifera tive effect on mesothelioma cell lines with a marked increase in cisplatin cytotoxicity. Therefore, the combined chemoimmunotherapy regimen is an wort hwhile approach to evaluate in a Phase II trial. METHODS. From December 1995 to June 1999, 37 previously untreated patients with MPM were treated with cisplatin 60 mg/m(2) intravenously on Day 1 plus doxorubicin 60 mg/m(2), recycled every 3-4 weeks and IFN-alpha -2b, 3 x 10 (6) international. units subcutaneously 3 times a week for a total of 6 cou rses or until progression. Inclusion criteria were histologic diagnosis of MPM and measurable disease defined by computed tomography scan or magnetic resonance imaging. RESULTS. Thirty-four patients were assessable for toxicity and 35 for effic acy according to World Health Organization criteria. One hundred thirty-fiv e courses were administered with a median of 4 cycles per patients. Seventy -six percent of patient presented at least 1 episode of severe myelosuppres ion (Grade 3 and 4). Severe anemia and thrombocytopenia occurred in 30% and 24% of patients, respectively. Sixty percent of patients presented constit utional symptoms. In the 35 patients assessable for response, the overall r esponse rate was 29% (95% confidence interval, 15-47%). The median duration of response was 8.4 months. With a median follow-up of 19.6 months, the me dian survival was 9.3 months. One- and 2-year survival was 45% and 34%, res pectively. CONCLUSIONS. This combined regimen has definite activity in MPM. However, t oxicity, particularly myelosuppression and fatigue, is not negligible and m ay limit its application. Cancer 2001;92:650-6. (C) 2001 American Cancer So ciety.