Phase II trial of neoadjuvant pemetrexed plus cisplatin followed by surgery and radiation in the treatment of malignant pleural mesothelioma (MPM).

Abstract

7090 Background: Combined modality approaches to therapy, including surgery (S) and radiation, have proved feasible and are becoming one of the standards of care in MPM. This study was designed to assess the efficacy of the combination of neoadjuvant pemetrexed+cisplatin, extrapleural pneumonectomy (EPP) and hemithoracic radiation (HTR) (trimodality [TM] therapy) in MPM. Methods: This was a multicenter, phase II, open-label study with event-free survival (EFS) (defined as time from enrollment to first observation of disease progression, death due to any cause or early treatment discontinuation) as the primary endpoint. Between 2005 and 2008, 56 patients (pts) with MPM (T1-3, N0-2) were screened, of whom 54 were enrolled (87% male; median age 63 [range 39-75] years; ECOG PS 0-1; adequate organ function). Pre-operative pemetrexed 500 mg/m2+cisplatin 75 mg/m2 IV was given every 21 days x 3 cycles, plus folic acid, vitamin B12 and dexamethasone, followed by EPP and HTR (total dose 54 Gy). After 2 deaths due to cardiopulmonary failure, occurred after HTR therapy (21 [38.8%] pts out of 54 were already enrolled in the study at this time), the protocol was amended reducing HTR dose to 50.4 Gy. Results: Of the 54 pts enrolled, 52 (96.3%) completed chemotherapy (CT), 45 (83.3%) underwent S, 22 (40.7%) completed the whole treatment including 90 day follow up. The median EFS was 6.9 months (95%CI: 5.0–10.5) and the median progression-free survival was 8.6 months (95%CI: 6.3-14.4). A total of 18 (33.3%) and 13 (24.1%) pts were still event free after 1 and 2 years respectively. Of the 54 pts, 16 (29.6%) showed partial response to CT, 31 (57.4%) showed stable disease, 4 (7.4%) showed progression, responses in 3 (5.6%) pts were unknown (overall response before S). During the whole study 36 (66.7%) pts experienced ≥1 grade 3-4 toxicity (the most frequent were hematological and gastrointestinal) but no statistically significant differences were observed before and after amendment. Conclusions: These results are aligned with the available scientific literature related to the TM approach on MPM, showing that the adopted multidisciplinary treatment is effective with a manageable toxicity profile.