Neoadjuvant Chemotherapy Followed by Extrapleural Pneumonectomy (EPP) for Malignant Pleural Mesothelioma (MPM): an Italian Experience with Cisplatin-Based Regimens

17022 Background: We have evaluated the feasibility and the impact on survival of two different preoperative chemotherapy regimens in potentially resectable MPM. METHODS Eligibility criteria were: histologically confirmed MPM, stage T1-3 N0-2 M0, adequate organ function, KPS ≥80. A first group of pts (group A) received cisplatin 75 mg/m2 d1 and gemcitabine 1200 mg/m2 d1,8, every 3 weeks for 4 courses, followed by EPP and by 6 courses of adjuvant chemotherapy with mitoxantrone 10 mg/m2 d1, methotrexate 35 mg/m2 d1 and mitomycin 7 mg/m2 d1, every 3 weeks with mitomycin in alternate cycles. A second group of pts (group B) received cisplatin 75 mg/m2 d1 plus pemetrexed 500 mg/m2 d1 with full vitamin supplementation for 4 cycles. In each group, only pts with metastatic lymph nodes and/or positive resection margins underwent radiotherapy after EPP. RESULTS Twenty-five pts were enrolled from February 2000 to August 2005 (8 in group A and 17 in group B). Pt characteristics were: 21 (84%) males and 4 (16%) females, asbestos exposure in 16 (64%) pts, median age 64 years (range, 51-72), median KPS 100 (80-100), histological subtype: 19 (76%) epithelial, 2 (8%) sarcomatous, 3 (12%) mixed, 1 (4%) unknown; IMIG stage: 6 (24%) I, 14 (56%) II, 5 (20%) III. Clinical response to neoadjuvant chemotherapy consisted of 4 (16%) CR, 2 (8%) PR, 11 (44%) SD, 5 (20%) PD; 3 (12%) pts were not evaluable. The overall response rate (CR + PR) was 24% (95% CI: 9.4 - 45.1). Toxicity was mild in each group. Fourteen (56%) pts have undergone EPP, 5 (20%) pleurectomy and 6 (24%) pts were inoperable. Three postoperative complications and two postoperative deaths (one for controlateral pneumonia and one for ARDS) occurred after EPP. The 1-year survival rate was 60%. Long-term survivors (≥18 months) included 5 pts who had undergone EPP (18, 26, 54, 57 and 63 months) and 2 pts who had undergone pleurectomy (22 and 32 months). CONCLUSIONS These preliminary data, albeit in a small series, suggest that preoperative chemotherapy followed by EPP is a feasible approach to be investigated in larger trials in pts with MPM. No significant financial relationships to disclose.