Development of target-based antineoplastic agents

The elucidation of multiple potential targets in cancer cells and the devel opment of multiple target-based antineoplastic agents provide unique challe nges in clinical trial design. Many of these agents are predicted to have c ytostatic as opposed to cytotoxic effects and thus the traditional surrogat e endpoint of radiologic tumor shrinkage may be inadequate. The ethical and safety issues of obtaining multiple tumor biopsies further complicate the assessment of appropriate target inhibition in patients. We discuss specifi c issues that need to be addressed during preclinical, phase I, II, and III testing of these agents. We propose clinical trial designs, including a ra ndomized discontinuation design during phase II evaluation, that may be par ticularly useful for cytostatic antineoplastic agents.