Asbestos Research Today is a free monthly online journal that collates and summarizes the latest research about Asbestos, including details on mesothelioma, lung disease, dangers, effects, risks.

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

Nakagawa K, Yamazaki K, Kunitoh H, Hida T, Gemba K, Shinkai T, Ichinose Y, Adachi S, Nambu Y, Saijo N, Fukuoka M

Kinki University School of Medicine, Medical Oncology, 377-2 Ohnohigashi, Osakasayama 589-8511, Japan. nakagawa@med.kindai.ac.jp

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.

Published 20 May 2008 in Jpn J Clin Oncol, 38(5): 339-46.
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