Trimodality therapy for malignant pleural mesothelioma: results from an EORTC phase II multicentre trial

Abstract

The European Organisation for Research and Treatment of Cancer (EORTC; protocol 08031) phase II trial investigated the feasibility of trimodality therapy consisting of induction chemotherapy followed by extrapleural pneumonectomy and post-operative radiotherapy in patients with malignant pleural mesothelioma (with a severity of cT3N1M0 or less).Induction chemotherapy consisted of three courses of cisplatin 75 mg?m -2 and pemetrexed 500 mg?m -2 . Nonprogressing patients underwent extrapleural pneumonectomy followed by postoperative radiotherapy (54 Gy, 30 fractions). Our primary end-point was ''success of treatment'' and our secondary end-points were toxicity, and overall and progression-free survival. 59 patients were registered, one of whom was ineligible. Subjects' median age was 57 yrs. The subjects' TNM scores were as follows: cT1, T2 and T3, 36, 16 and six patients, respectively; cN0 and N1, 57 and one patient, respectively. 55 (93%) patients received three cycles of chemotherapy with only mild toxicity. 46 (79%) patients received surgery and 42 (74%) had extrapleural pneumonectomy with a 90-day mortality of 6.5%. Post-operative radiotherapy was completed in 37 (65%) patients. Grade 3-4 toxicity persisted after 90 days in three (5.3%) patients. Median overall survival time was 18.4 months (95% CI 15.6-32.9) and median progression-free survival was 13.9 months (95% CI 10.9-17.2). Only 24 (42%) patients met the definition of success (one-sided 90% CI 0.36-1.00).Although feasible, trimodality therapy in patients with mesothelioma was not completed within the strictly defined timelines of this protocol and adjustments are necessary.

Multimodal management of malignant pleural mesothelioma: where are we today?

“…The EORTC initiated a phase II trial to evaluate the feasibility of trimodal therapy in a multicentre international setting (EORTC 08031) with clearly defined timelines [43]. Patients with pathologically proven mesothelioma of stage cT3N1M0 or less underwent induction chemotherapy consisting of three cycles of cisplatin and pemetrexed followed by EPP within 21-56 days after the last dose of chemotherapy if there was no progressive disease and no unacceptable toxicity.…”

Randomized controlled trials in malignant pleural mesothelioma surgery—mistakes made and lessons learned

“…Their apparent benefit is based on completed treatments rather than on intention to treat; patients who do poorly do not complete the protocol and are thus not included in the final analysis (2). Nevertheless, their results can be used to shape future surgical trial protocols by excluding poorly tolerated regimes i.e., European Organisation for Research and Treatment of Cancer (EORTC) trial 08031 which showed the difficulty in tri-modality therapy including extrapleural pneumonectomy (EPP) (3).…”

Novel systemic therapy against malignant pleural mesothelioma

“…Younger patients with good performance status, epithelioid histology, and localized resectable disease can generally be offered multimodality therapy with systemic chemotherapy, surgical resection, and sometimes radiation therapy (28,29). Another article in this issue of Translational Lung Cancer Research discusses surgical options for MPM; however, we will briefly mention here that surgical options are generally limited to patients with the epithelioid subtype of MPM and consist of pleurectomy/decortication (P/D) with mediastinal lymph node sampling or extrapleural pneumonectomy (EPP).…”