PROSPECTIVE-STUDY OF COMBINATION CHEMOTHERAPY WITH CYCLOPHOSPHAMIDE, DOXORUBICIN, AND CISPLATIN FOR UNRESECTABLE OR METASTATIC MALIGNANT PLEURAL MESOTHELIOMA

Background. This study was designed to determine the efficacy and side effects of a combination of cyclophosphamide (C), doxorubicin (D), an d cisplatin (P) in patients with inoperable, unresectable, or metastat ic malignant pleural mesothelioma, Methods. Twenty-three patients with unresectable or metastatic malignant pleural mesothelioma were entere d onto the study. The median age was 62 years (range, 42-74 years); th ere were 20 males and 3 females; the median performance status was 1 ( Zubrod's scale). The histologic types included epithelial (14 patients ), sarcomatoid (4 patients), unclassified (4 patients), and mixed type (1 patient). Twenty patients were known to have been exposed to asbes tos and 3 were not. All patients were treated with the following start ing dose of chemotherapy: a cycle comprised of C, 500 mg/m(2) intraven ously, day 1; D, 50 mg/m(2) intravenously, day 1; and P, 80 mg/m(2) in travenously, day 1 every 3 weeks. The cisplatin dose was reduced to 50 mg/m2 for the subsequent courses, For the assessment of tumor respons e, all patients had computed tomography scans of the chest after each three cycles of chemotherapy. Results. Overall, 7 of 23 patients (30%) had partial responses (durations of responses [weeks]: 158+, 91+, 70, 41+, 40, 39, 25), three had minor responses, and 14 had stable or pr ogressive disease, One partial responder later underwent surgical rese ction and no viable tumors cells were found in the pathologic specimen . All patients have stopped treatment, and eight are still alive. The most common side effect was granulocytopenia (grade 4, 52%; grade 3, 1 7%). Other hematologic side effects were modest. Nonhematologic side e ffects included mild to moderate nausea and vomiting, neutropenic feve r (three patients), peripheral neuropathy (one patient), and congestiv e heart failure (one patient). The overall median duration of survival was 60 weeks, Conclusion. Combination chemotherapy with CDP was well tolerated and had significant activity against unresectable or metasta tic malignant pleural mesothelioma. The median duration of responses w as 60 weeks; however, the survival rate was far from satisfactory. Con tinued development of new approaches including the biologic understand ing of tumor development and testing new agents is warranted.