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

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.

• Authors: Kazuhiko Nakagawa, Koichi Yamazaki, Hideo Kunitoh, Toyoaki Hida, Kenichi Gemba, Tetsu Shinkai, Yukito Ichinose, Susumu Adachi, Yoshihiro Nambu, Nagahiro Saijo, Masahiro Fukuoka
• Journal: Japanese journal of clinical oncology (Jpn J Clin Oncol) Vol. 38 Issue 5 Pg. 339-46 (May 2008) ISSN: 1465-3621 [Electronic] England
• PMID: 18434338 (Publication Type: Clinical Trial, Phase I, Clinical Trial, Phase II, Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)

Chemical References

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

Topics

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