Phase I studies of chemotherapeutic agents in cancer patients: a review of the designs.

I review the designs available for Phase I dose-finding studies of chemotherapeutic agents in cancer patients. The designs are based on the assumption that both efficacy and toxicity increase with dose, and thus attempt to minimize the number of patients treated at low doses, and also to minimize the chance that patients will be treated at excessively toxic or lethal doses. The designs fall into two classes: rule-based and model-guided. Rule-based designs can always determine a reasonable maximum tolerable dose based on observed toxicity, but when model assumptions are not satisfied, many model-guided designs will not.