Phase II feasibility trial of induction chemotherapy (ICT) followed by extrapleural pneumonectomy (EPP) and postoperative radiotherapy (PORT) for cT3N1M0 or less malignant pleural mesothelioma (MPM) (EORTC 08031)

Abstract

7509 Background: MPM is a highly lethal disease and the role of EPP in the treatment of early stage, potentially resectable MPM remains controversial. EORTC 08031 phase II trial investigated the feasibility of trimodality therapy (TMT) consisting of ICT followed by EPP and PORT. Methods: Eligibility criteria were cT3N1M0 or less, proven MPM, < 70 years, PS 0–1, fit for TMT. ICT consisted of 3 courses of cisplatin 75mg/m2 and pemetrexed 500mg/m2 q3weeks. Non-progressing patients (pts) underwent EPP followed by PORT (54Gy, 30 fractions). Primary endpoint was “success of treatment” defined as a patient receiving the full protocol treatment, still alive 90 days after end of treatment without progression and without grade (G) 3–4 toxicity. Using a one step Fleming design 52 patients and 26 successes were required. Secondary endpoints were toxicity of TMT, overall and progression-free survival. Results: 59 pts were registered between 07/26/05 and 08/24/07, 1 was ineligible. Median age was 57 years (range 26–67), M/F 46/12, all proven MPM (31 epithelial, 18 mixed, 9 other). All pts underwent mediastinoscopy, cT1/T2/T3: 36/16/6, cN0/N1: 57/1. 55 pts received 3 cycles of ICT. G3–4 toxicity related to ICT was rare. 46 pts (79%) were operated, 42 (74%) had EPP. R0/1/2: 30/10/3, 6 were re-operated, pT0/1/2/3/4: 2/5/19/15/4, pN0/1/2/3: 34/2/6/2, 90-day mortality: 3 pts (6.5%); in 38 pts (83%) postoperative complications occurred. PORT was initiated in 38 pts and completed in 37 (65%). After PORT 2 pts (3.5%) died due to infection. Persisting G3/4 toxicity after 90 days: 3 pts (5.3%) due to radiation pneumonitis and bronchopleural fistula. After median follow- up of 19.3 months (mos) median overall survival time was 18.4 mos (95% CI 14.8-NR) and median progression-free survival was 13.9 mos (95% CI 10.9–17.1). Only 24 pts (42%) met the definition of success (one-sided 90% CI 0.36–1.00). Conclusions: EORTC 08031 investigated the feasibility of TMT in pts with proven MPM. Due to the low proportion of “successes” this TMT is not considered to be feasible. Although overall results were similar to other series, adjustments to this TMT are necessary. No significant financial relationships to disclose.