Efficacy and safety of pemetrexed in combination with cisplatin for malignant pleural mesothelioma: a phase I/II study in Japanese patients

Jpn J Clin Oncol. 2008 May;38(5):339-46. doi: 10.1093/jjco/hyn024. Epub 2008 Apr 22.

Abstract

Background: Pemetrexed in combination with cisplatin (Pem/Cis) is used globally for the treatment of malignant pleural mesothelioma (MPM). This Phase I/II study was conducted to determine the recommended dose (RD) (Phase I) of Pem/Cis, and evaluate the efficacy and safety (Phase II) in Japanese MPM patients.

Methods: Key eligibility criteria were histologic diagnosis of MPM incurable by surgery, no prior chemotherapy, and a performance status 0-1. Under full vitamin supplementation, pemetrexed was intravenously administered on Day 1 of a 21-day cycle, followed by cisplatin. A cohort of six patients, starting from pemetrexed 500 mg/m(2) and cisplatin 75 mg/m(2) (Level 1), were studied in the dose-escalation Phase I (Step 1). The RD determined in Step 1 was carried forward into Phase II (Step 2). Planned number of patients treated with Pem/Cis was 18-38.

Results: In Step 1, 13 patients were enrolled: seven in Level 1 and six in Level -1 (pemetrexed 500 mg/m(2), cisplatin 60 mg/m(2)). Two of six evaluable patients had dose-limiting toxicities (pneumonitis and neutropenia) in Level 1, establishing Level 1 as the RD. In Step 2, 12 patients were enrolled, for a total of 19 patients treated at the RD. Seven patients achieved a partial response among these patients, for a response rate of 36.8% (95% confidence interval: 16.3-61.6); overall survival was 7.3 months. One drug-related death occurred due to worsening of a pre-existing pneumonia. Common grade 3/4 toxicities were neutropenia and decreased-hemoglobin.

Conclusion: The Pem/Cis combination provides promising activity and an acceptable safety profile for chemonaive Japanese MPM patients with the same recommend dosage and schedule used in rest of the world.

Publication types

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

MeSH terms

  • Adult
  • Aged
  • Antimetabolites, Antineoplastic / administration & dosage
  • Antimetabolites, Antineoplastic / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage*
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects*
  • Cisplatin / administration & dosage
  • Cisplatin / adverse effects
  • Disease-Free Survival
  • Drug Administration Schedule
  • Female
  • Folic Acid Antagonists / administration & dosage
  • Folic Acid Antagonists / adverse effects
  • Glutamates / administration & dosage
  • Glutamates / adverse effects
  • Guanine / administration & dosage
  • Guanine / adverse effects
  • Guanine / analogs & derivatives
  • Humans
  • Infusions, Intravenous
  • Japan
  • Kaplan-Meier Estimate
  • Male
  • Mesothelioma / drug therapy*
  • Mesothelioma / physiopathology
  • Middle Aged
  • Pemetrexed
  • Pleural Neoplasms / drug therapy*
  • Pleural Neoplasms / physiopathology
  • Quality of Life
  • Respiratory Function Tests
  • Treatment Outcome

Substances

  • Antimetabolites, Antineoplastic
  • Folic Acid Antagonists
  • Glutamates
  • Pemetrexed
  • Guanine
  • Cisplatin