Bulletin du cancer
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The purpose of phase II trials is to identify signals in favor of the efficacy of a drug in development. The main pitfall of a phase II study is to conclude by error that a drug has no activity, leading to a stop in the development of a drug which has a real efficacy. ⋯ This bias consists of recruiting by chance a population of patients with high risk or on the contrary low risk of response to the experimental treatment. The present paper describes the various types of randomised phase II trials, their principles, strengths and limits.
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The methodological principles for the planning of interim analyses in a phase III clinical trial are presented in this article. The case for superiority, non-inferiority and futility, and the roles of Data Monitoring Committees are summarized. Several examples are presented to illustrate the methodology and to help investigators by better understanding and planning interim analyses in a phase III clinical trial.
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The main objective of phase I cancer trials is to determine precisely the recommended dose of an anticancer agent as a single agent or in a context of combinations of anticancer agents (including cytotoxic agents, immunotherapy, radiotherapy...), that is administered for the first time in man, to further proceed clinical development with phase II and III trials. The recommended dose must have the greatest efficiency with acceptable toxicity. For the anticancer agents, the ratio risk/benefit is high, since toxicities associated with many cancer therapeutic agents are substantial and because the efficacy is often limited. ⋯ Concerning the targeted anticancer therapies, the therapeutic effect on the target, due to their higher specificity, can be obtained using doses that have few toxicity. Using the toxicity to determine the recommended dose for phase II trials, as it is the case for "classical >> anticancer agents, does not seem to be sufficient. Alternatives to determine the optimal biological dose include measurement of target inhibition, pharmacokinetic analysis and functional imaging.