Development of Target-Based Antineoplastic Agents

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Abstract
The elucidation of multiple potential targets in cancer cells andthe development of multiple target-based antineoplastic agentsprovide unique challenges in clinical trial design. Many of theseagents are predicted to have cytostatic as opposed to cytotoxiceffects and thus the traditional surrogate endpoint of radiologictumor shrinkage may be inadequate. The ethical and safety issuesof obtaining multiple tumor biopsies further complicate theassessment of appropriate target inhibition in patients. Wediscuss specific issues that need to be addressed duringpreclinical, phase I, II, and III testing of these agents. Wepropose clinical trial designs, including a randomizeddiscontinuation design during phase II evaluation, that may beparticularly useful for cytostatic antineoplastic agents.