The employment of combinations of drugs in the chemotherapy of neoplasia: a review.

Studies on the effectiveness of drug combina tions have intrigued pharmacologists for decades. Combinations of drugs have been used in attempts to attain enhanced biological effects. The range of pharmacological interests in which drug combina tions have been studied is diverse, including anal gesics, insecticides, fungicides, antibiotics, plant and animal hormones, cellular poisons, etc. The recent review by Veldstra (76) may be consulted for the detailing of the numerous areas of interest and for references on drug combinations pertain ing to phenomena of synergism and potentiation. The methods currently employed in investigat ing the effectiveness of drug combinations in the chemotherapy of neoplasia represent an outgrowth and development of earlier methods of combina tion drug research. The early medical interest in the employment of drugs in combination was in an attempt to improve therapy. The general con cept was that, by the employment of two drugs, lower doses of each could be used, undesirable toxic side effects would be reduced, and there would be a greater margin of safety. Alternatively, drugs would be used in combination in order to take advantage of the separate effects of each, e.g., the rapidity of onset of one drug and the prolonged duration of the other. The early trials with drug combinations were somewhat empirical, with relatively little attempt at quantification. The emphasis, however, was clearly on attaining "therapeutic synergism," that is, the achieving of