Japanese Journal of Clinical Oncology Advance Access published online on April 22, 2008
Japanese Journal of Clinical Oncology, doi:10.1093/jjco/hyn024
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© The Author (2008). Published by Oxford University Press. All rights reserved
Efficacy and Safety of Pemetrexed in Combination with Cisplatin for Malignant Pleural Mesothelioma: A Phase I/II Study in Japanese Patients
1 Kinki University School of Medicine, Department of Medical Oncology, Osakasayama, Osaka
2 Hokkaido University School of Medicine, First Department of Medicine, Sapporo
3 National Cancer Center Hospital, Department of Internal Medicine and Thoracic Oncology, Tokyo
4 Aichi Cancer Center Hospital, Department of Thoracic Oncology, Nagoya
5 Okayama Rosai Hospital, Department of Respiratory Medicine, Okayama
6 NHO Shikoku Cancer Center, Department of Medicine and Thoracic Oncology, Matsuyama
7 National Kyushu Cancer Center, Department of Thoracic Oncology, Fukuoka, Japan
8 Eli Lilly and company, Lilly Research Laboratories, Indianapolis, IN, USA
9 Eli Lilly Japan K.K., Lilly Research Laboratories Japan, Kobe
10 National Cancer Center Hospital East, Kashiwa, Chiba, Japan
For reprints and all correspondence: Kazuhiko Nakagawa, Kinki University School of Medicine, Medical Oncology, 377-2 Ohnohigashi, Osakasayama 589-8511, Japan. E-mail: nakagawa{at}med.kindai.ac.jp
Received October 3, 2007; accepted March 1, 2008
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/m2 and cisplatin 75 mg/m2 (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/m2, cisplatin 60 mg/m2). 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.
Key Words: cisplatin • mesothelioma • pemetrexed • phase I/II