Mesothelioma Research Today is a free monthly online journal that collates and summarizes the latest research about Mesothelioma, including details on asbestos, symptoms, treatment, causes.

Phase II trial of pralatrexate (10-propargyl-10-deazaaminopterin, PDX) in patients with unresectable malignant pleural mesothelioma.

Krug LM, Heelan RT, Kris MG, Venkatraman E, Sirotnak FM

Thoracic Oncology Service, Division of Solid Tumor Oncology, Department of Medicine, Memorial Sloan-Kettering Cancer Center, Weill Medical College of Cornell University, New York, New York 10021, USA. krugl@mskcc.org

BACKGROUND: Several previous clinical trials have shown that malignant pleural mesothelioma is responsive to antifolates. The dihydrofolate reductase inhibitor, pralatrexate, has a favorable toxicity profile, primarily limited to stomatitis, and has demonstrated activity in patients with non-small cell lung cancer. In mesothelioma cell lines and xenografts, pralatrexate demonstrated significant antitumor activity. METHODS: We conducted this phase II study to determine the response rate of malignant pleural mesothelioma to pralatrexate at a dose of 135 mg/m2 i.v. every 2 weeks. After a protocol amendment, patients were supplemented with vitamin B12 and folic acid at the time of starting therapy. RESULTS: A total of 16 assessable patients were enrolled. No complete or partial responses were observed. Two patients with epithelioid histology had minor responses. Three other patients remained on study with stable disease for 9, 9, and 48 months. The median time to progression was 3 months. The overall median survival time was 7 months (95% confidence interval: 3.2-16.2 months) and the one-year survival was 31% (95% confidence interval: 15%-65%). Three patients (19%) had grade 2 stomatitis, eight (50%) had grade 3, and one (6%) had grade 4. CONCLUSIONS: With this particular dose and schedule, pralatrexate as a single agent had no activity in malignant pleural mesothelioma.

Published 5 April 2007 in J Thorac Oncol, 2(4): 317-20.
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