Application of theoretical models to chemotherapy protocol design.

The somatic mutation model of cancer chemotherapy predicts that under certain conditions some sequences of chemotherapy drug administration will be superior to others. Alternation between two non-cross-resistant combinations that are equivalent in effectiveness is one such sequence. This method was utilized in a number of clinical trials based primarily on intuitive perceptions on how treatment failure due to drug resistance can be minimized. A survey of a number of recently published trials employing some form of alternating chemotherapy indicates that a majority of them suggested an advantage to this approach compared to sequential therapy, although in most studies this benefit was small. Most of the studies, whether or not supportive of the concept of alternating therapy, could not be considered a fair test of the theory. Reference to theoretical models of chemotherapeutic action may provide assistance in devising clinical trials that will rigorously test the concept of alternating chemotherapy to see to what extent this technique will improve treatment results in selected neoplasms.