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Developmental therapeutics and the design of clinical trials

  • Robert K. Oldham
Chapter

Abstract

New techniques in biotechnology and the use of biologicals in cancer treatment have made it apparent that there are differences in developmental therapeutics for biotherapy, in contrast to drug development. Over the past 25 years more than one million chemicals have been screened as anticancer agents, but less than 60 have reached the clinic as commercial pharmaceuticals. Perhaps 10 of these drugs can be classed as moderately effective; the rest are only marginally useful and all can be highly toxic. With the discovery of monoclonal antibodies and conjugates thereof, the exploitation of bioengineering to produce purified, characterized lymphokines/cytokines and other biologicals, and further information on the mechanism of action of these natural molecules, the rate of development for biological therapeutics has risen dramatically. Because of their selectivity, and with the implicit biological diversity of cancer, new approaches are needed to efficiently bring biotherapy to the clinic. Previously, there have always been fewer promising agents (drugs) to test than patients who needed new approaches. In fact, the drug development paradigm has been a slow and laborious mechanism of developmental therapeutics prior to 2000 with each drug taking some 8–12 years to commercial approval, at a cost of 300–500 million dollars. These extraordinary costs have resulted in only two to 10 anticancer drugs coming into the system annually. Far fewer have been approved for use. Taxol, a recent drug approved for general use, entered clinical trials in the late 1980s and only became generally available in 1998; taking more than a decade to pass through our current system of drug development. On average, fewer than two chemotherapy drugs per year have been approved for general use by oncologists. This expensive and slow paradigm reflects both the toxicity and marginal effectiveness of chemotherapeutic drugs as well as a bureaucratic regulatory system more fearful of criticism over toxicity than a willingness to pursue opportunities for seriously ill patients [57, 58, 70].

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