Pleurectomy, intrapleural cisplatin and interferon followed by systemic carboplatin plus interferon in malignant pleural mesothelioma

Malignant pleural mesothelioma has a dismal prognosis and median survival rarely exceeds 12 months. Since multimodality therapy initially showed promising results, we tested the feasibility of a new approach consisting of pleurectomy, immediately followed by intrapleural chemotherapy with cisplatin (100 mg/m(2) day 1) and alpha-interferon (12x10(6) U/m(2) days 1 and 2), followed by 4 cycles of carboplatin, 350 mg/m(2), repeated every 3 weeks and associated to alpha-interferon (3x10(6) U/x3/week). Fourteen patients have been submitted to the protocol and are evaluable for side effects. All patients had surgery and intrapleural chemotherapy, and 4 patients also had systemic chemotherapy. No treatment-related deaths have been observed. Major postoperative complications included chest tube air leak >7 days (1 pt). Intracavitary chemo-immunotherapy-related toxicity was responsible for 7 cases of grade I nephro-toxicity and 2 cases of grade I fever. Grade I-II toxicity from systemic chemotherapy included asthenia (2 cases), fever (3 cases), anemia (2 cases) and neutropenia (2 cases). Grade III-IV toxicity included asthenia (1 case), anemia (2 cases), neutropenia (2 cases) and fever (1 case). Two cases required interruption of systemic chemotherapy for intolerance. Based on these data, systemic chemotherapy has been stopped. In conclusion, our results indicate that pleurectomy plus intra-cavitary cisplatin and interferon is feasible. Since systemic chemotherapy is correlated with severe side effects, a phase II trial with surgery plus intrapleural treatment alone is ongoing.