Multicenter phase II trial of neoadjuvant pemetrexed plus cisplatin followed by extrapleural pneumonectomy and radiation for malignant pleural mesothelioma

J Clin Oncol. 2009 Jun 20;27(18):3007-13. doi: 10.1200/JCO.2008.20.3943. Epub 2009 Apr 13.

Abstract

Purpose: Neoadjuvant pemetrexed plus cisplatin was administered, followed by extrapleural pneumonectomy (EPP) and hemithoracic radiation (RT), to assess the feasibility and efficacy of trimodality therapy in stage I to III malignant pleural mesothelioma.

Patients and methods: Requirements included stage T1-3 N0-2 disease, no prior surgical resection, adequate organ function (including predicted postoperative forced expiratory volume in 1 second > or = 35%), and performance status 0 to 1. Patients received pemetrexed 500 mg/m(2) plus cisplatin 75 mg/m(2) for four cycles. Patients without disease progression underwent EPP followed by RT (54 Gy). The primary end point was pathologic complete response (pCR) rate.

Results: Seventy-seven patients received chemotherapy. All four cycles were administered to 83% of patients. The radiologic response rate was 32.5% (95% CI, 22.2 to 44.1). Fifty-seven patients proceeded to EPP, which was completed in 54 patients. Three pCRs were observed (5% of EPP). Forty of 44 patients completed irradiation. Median survival in the overall population was 16.8 months (95% CI, 13.6 to 23.2 months; censorship, 33.8%). Patients completing all therapy had a median survival of 29.1 months and a 2-year survival rate of 61.2%. Radiologic response of complete or partial response was associated with a median survival of 26.0 months compared with 13.9 months for patients with stable disease or progressive disease (P = .05).

Conclusion: This multicenter trial showed that trimodality therapy with neoadjuvant pemetrexed plus cisplatin is feasible with a reasonable long-term survival rate, particularly for patients who completed all therapy. Radiologic response to chemotherapy, but not sex, histology, disease stage, or nodal status, was associated with improved survival.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Agents / administration & dosage*
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Cisplatin / administration & dosage*
  • Combined Modality Therapy
  • Female
  • Glutamates / administration & dosage*
  • Guanine / administration & dosage
  • Guanine / analogs & derivatives*
  • Humans
  • Male
  • Mesothelioma / mortality
  • Mesothelioma / radiotherapy
  • Mesothelioma / therapy*
  • Middle Aged
  • Neoadjuvant Therapy
  • Pemetrexed
  • Pleural Neoplasms / mortality
  • Pleural Neoplasms / radiotherapy
  • Pleural Neoplasms / therapy*
  • Pneumonectomy*

Substances

  • Antineoplastic Agents
  • Glutamates
  • Pemetrexed
  • Guanine
  • Cisplatin