Clin Cancer Res
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This report describes the data and analysis leading to the approval of pemetrexed (LY 231514, MTA, Alimta, Eli Lilly and Co., Indianapolis, IN) by the U.S. Food and Drug Administration (FDA) of a New Drug Application for the treatment of malignant pleural mesothelioma (MPM). ⋯ Pemetrexed in combination with cisplatin was approved by the FDA on February 4, 2004 for the treatment of patients with MPM whose disease is either unresectable or who are otherwise not candidates for curative surgery. The recommended dose of pemetrexed is 500 mg/m(2) intra venous infusion over 10 minutes on day 1 of each 21-day cycle in combination with 75 mg/m(2) cisplatin infused over 2 hours beginning 30 minutes after the pemetrexed infusion. Patients must receive oral folic acid and vitamin B(12) injections before the start and during therapy to reduce severe toxicities. Patients should also receive corticosteroids with the chemotherapy to decrease the incidence of skin rash. Approval was based on a demonstration of survival improvement in a single randomized trial. Response rates and time to tumor progression were not included in product labeling because of inconsistencies in assessments among the investigators, independent radiologic reviewers, and the FDA, reflecting the difficulty of radiographic assessments in malignant mesothelioma. Complete prescribing information is available on the FDA Web site at http://www.fda.gov/cder/approval/index.htm.
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The number of anticancer agents that fail in the clinic far outweighs those considered effective, suggesting that the selection procedure for progression of molecules into the clinic requires improvement. The value of any preclinical model will ultimately depend on its ability to accurately predict clinical response. This review focuses on the major contributions of preclinical screening models to anticancer drug development over the past 50 years. ⋯ Europe has played a key role in the development of new anticancer agents. The two largest academic drug development groups, the European Organisation for Research and Treatment of Cancer and Cancer Research UK, have been collaborating with the NCI in the acquisition and screening of compounds since the 1970s. As with the drug development process internationally, rational pharmacodynamic approaches have more recently been adopted by these two groups.