Drug combinations, } alone or in conjunction with surgery and/or radiationJ

Figure 20.5 Outline of the flow of clinical trials in the early phases of testing of new drugs for potential use in cancer chemotherapy.

Figure 20.6 Scheme outlining the overall pharmacologic-therapeutic process from drug dose to a therapeutic effect, which in cancer chemotherapy is destruction and/or elimination of neoplastic cells. (Adapted from Bjornsson, 1996, with permission of the author and publishers.)

dysfunction, hypersensitivity reactions, and dermatological complications as well as alopecia (loss of hair) occur not uncommonly as toxic manifestations of a number of chemotherapeutic regimens.

The relationship between the probability of some biological or toxic effect of a drug and the dose administered to induce antineoplastic efficacy may be seen in Figure 20.7. As noted, if the drug is to be useful, the "antitumor effect" curve, ideally giving complete clinical remission, should be displaced toward lower doses compared with the curve describing the probability of significant toxicity to normal tissue. The therapeutic index (or therapeutic ratio) may be defined

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