A Multicenter U.S. Trial Of Neoadjuvant Pemetrexed Plus Cisplatin (PC) Followed By Extrapleural Pneumonectomy (EPP) And Hemithoracic Radiation (RT) For Stage I-III Malignant Pleural Mesothelioma (MPM)
Background: The optimal management for fit patients with early stage MPM remains controversial. One approach involves neoadjuvant chemotherapy followed by EPP and hemithoracic RT and prior trials using gemcitabine and cisplatin have been reported (Weder JCO 2004, Flores JTO 2006). We administered PC, followed by EPP and RT to further assess feasibility and survival of trimodality therapy in a larger, multicenter study. Methods: Eligibility criteria: Stage T1–3 N0–2, no prior surgical resection, adequate organ function (including predicted post-op FEV1 >35%) and PS 0–1. Pts received pemetrexed 500 mg/m2 plus cisplatin 75 mg/m2 with vitamin supplementation for 4 cycles. Pts without disease progression underwent EPP followed by RT (54 Gy). The primary endpoint was pathologic complete response (pCR) rate. Enrollment was completed in March, 2006. Results: 77 patients were enrolled and 72 are evaluable. Median age 63.5 (range 34–78), M:F = 51:21, Clinical stage I:II:III:IV = 5:31:33:1, epithelial:nonepithelial = 58:15, ECOG PS 0:1:2 = 28:42:2. 83% of patients completed all four cycles of PC. Grade 3/4 events related to chemotherapy included: neutropenia (4%), febrile neutropenia (3%), nausea (1%), vomiting (3%), pneumonia (6%), pulmonary embolism (1%), and chest pain (3%). Of 73 pts assessed for radiologic response, 3 CRs, 21 PRs, 36 SDs, 3 PDs, and 10 were unevaluable; (RR= 33% [95% CI, 0.22, 0.45]). Of 54 pts who underwent surgery, EPP completion rate was 87% (47/54); that is 47/77 (61%) by ITT. Pathologic stage I:II:III:IV:NE = 4:12:24:3:11. One pCR was confirmed. 35/39 completed RT. Preliminary TTP =13.1 mo (95% CI=9.6, 15.9; 48% censored) and median survival=16.6 mo (95% CI=13.9, 19.3; 55% censored;1-yr survival = 68%). Conclusions: This multicenter trial testing trimodality therapy in MPM showed that it is feasible with a high rate of chemotherapy delivery. One pCR was observed. Preliminary survival is below that reported by single institutions for patients undergoing EPP but with a high censorship rate at this early time point. Further analyses are necessary to identify a cohort of patients most likely to benefit. This study was sponsored by Eli Lilly & Company.
No significant financial relationships to disclose.