EXPERIMENTAL-DESIGN CONSIDERATIONS IN CLINICALLY COMBINING RADIATION AND DRUGS

Recently, combined modality approaches have been used to achieve superior results in either local regional control or disseminated disease control. When radiation therapy and chemotherapy are combined, the situation becomes complicated because drugs can potentially interact with radiation in 2 ways: (1) drugs can kill cells that radiation cannot and function as adjuvant to radiation cell kill, and (2) drugs can sensitize cells to the killing of radiation and increase the therapeutic ratio for radiation. The interaction of radiation therapy and chemotherapy has to be viewed as a balance of 2 general effects: antitumor action and toxicity. When drugs and X-ray are combined, it can be hoped that the drug will potentiate the effects of the irradiation for superior local and regional control, or that the drugs will have an adjuvant effect and kill tumor cells outside the range of the X-ray. The design of a combined modality study depends upon which of the 2 effects is being sought. The potentiation trial is easier to design because results can be judged soon after the completion of irradiation. The adjuvant trial has a more long-term evaluation process which could take several years of follow-up study. Where both potentiation and adjuvant cell kill are possible, the analysis becomes complicated because it is not possible to separate out whether potentiation or adjuvant cell kill was the result. In combined modality adjuvant clinical trials, the need for longterm analysis is an absolute prerequisite. However, this is complicated by the reality of the situation in which new trials need to be designed quickly as case accession to studies reaches estimated required numbers, and the need and pressure for an early analysis is severe. One of the problems in the evaluation and design of adjuvant trials is that some patients receive unneeded therapy as they are cured by their surgery and/or irradiation. © 1979.