With the discovery of a handful of drugs capable of temporarily restraining the relentless progress of cancer, curative chemotherapy was recognized as a scientifically feasible goal. The problems facing research investigators as they entered the decade of the 1960's revolved around the enormous task of choosing from among hundreds of thousands of synthetic and natural chemicals those few compounds with potential for curing human cancer and working out effective and safe methods for administering cancer drugs to patients.

At present, these are still the goals of cancer chemotherapy research. But during the 1960's, the ability of drugs to produce complete, long-term remissions, perhaps cures, in some patients with widespread, rapidly progressive cancer was unequivocally established. These results have been derived more and more frequently from truly quantitative laboratory and clinical investigations. Opportunity is thus afforded to extend the principles learned during these studies to tumor types not yet under drug control.

Study of the life history and biologic behavior of the various diseases comprising cancer continues to be intrinsic to the rational design of curative chemotherapy and to the treatment of patients with specific forms of cancer.

A particular problem in selection of drugs for clinical trial is the need for a preclinical screen which will identify agents that may be active against cancer in man. Such screens, which are usually animal tumors, can be used confidently only when, on the basis of extensive data, it can be shown that there is a good correlation between antitumor effect in the screen and in one or more types of human cancer. Similarly, it is recognized that pharmacological studies comparing drug effects in animal systems and man are needed to permit prediction of safe dosage and possible side effects in patients.

A major problem posed in studies of new drugs is the degree of risk to the patient. A stage ultimately is reached when conventional methods of treatment can no longer be used. At such time clinical trial with a selected new drug according to a well designed experimental plan and utilizing all modern means of auxiliary therapy, such as blood platelet transfusions when necessary, is acceptable both to the physician and patient.

Nevertheless, the philosophy that the individual patient's best interests are paramount is the guiding principle of modern clinical investigation of cancer drugs. No treatment of proved value is denied a patient merely to permit the study of a new method of treatment. In considering new drugs, the physician weighs the risks against the benefits that may attend their use. His decision must maximize the possibility that the life of a patient beyond cure can be qualitatively enhanced even if not prolonged. Also, an individual patient who would be harmed by continuing in a study is shifted to another type of therapy, and the protocol of a study should be amended if during the course of it unanticipated difficulties arise. Experience has shown that adherence to these principles in no way necessitates a departure from sound scientific appraisal of a new drug.

The time will come when problems will arise as a result of successes with drug treatment. Clinical investigators may decide to use drugs much earlier in the course of the disease, before patients are beyond the hope of cure through surgery and radiation therapy; or they may test new drugs before established ones have failed in the diseases such as leukemia which are disseminated at the outset. Drug treatment of choriocarcinoma is sufficiently effective so that it may be used in preference to surgical removal of the uterus in patients with localized disease; the child-bearing capability of young women can thus be preserved. The principles of weighing risks and benefits for the prolongation of useful life will continue to prevail in the coming decades.