Despite increases in drug development expenditures in the public and private sectors during the 1990s, the number of new agents reaching human clinical trials has been decreasing. Even when compounds proceed to clinical testing, they often fail because of unexpected toxicities or lack of efficacy. The pathway from discovery of promising agents to delivery in the oncology clinic, though multifaceted and complex, may change due to improvements in our understanding of drug targeting at the molecular level. Modern drug development techniques that employ imaging and other advances also make foreseeable the arrival of screening tools that could, early in the pathway, predict therapeutic or toxic activity in humans. Such changes should shorten the amount of time it takes to bring useful new anticancer drugs to the patients who need them.
The Division of Cancer Treatment and Diagnosis (DCTD) is reexamining its discovery and development paradigm. Pharmacokinetic and pharmacodynamically (PK/PD)–guided clinical trials are being emphasized in conjunction with assays of specific molecular targets. Such studies are already used to examine the biological effects of drugs in animals and humans. By studying PK/PD responses, researchers will be better able to administer the appropriate dose to achieve the desired therapeutic response with a minimum risk of toxic effects.