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Drug Interactions in Cancer Chemotherapy

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Concepts in Biochemical Pharmacology

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Abstract

As a result of clinical research over the last ten years, the simultaneous use of multiple pharmacologic agents in the therapy of malignant disease has become the accepted form of treatment for acute leukemia (Holland, 1968), advanced Hodgkin’s disease (Devita et al., 1970), lymphosarcoma (Bagley et al., 1972), and other tumors (Cooper, 1969; James et al., 1965). These therapeutic advances were largely the outgrowth of earlier experiences with single agents, which despite obvious antitumor activity, elicited incomplete responses or complete remissions of only brief duration. The limitations of single drug therapy were two-fold: (1) the toxicity of the drug limited the amount and duration of drug exposure tolerated by the host, and thus restricted cell kill, and (2) adaptive mechanisms allowed survival and proliferation of a fraction of resistant neoplastic cells despite a metabolic block lethal to the bulk of the tumor. Noting the effectiveness of combined chemotherapy in infectious diseases such as malaria (Blount, 1967), tuberculosis (Barry, 1964), and enterococcal bacterial endocarditis (Lerner and Weinstein, 1966), oncologists reasoned that the use of several active agents in combination might produce greater cell kill, while delaying the appearance of resistance to the individual drugs. The success of such combinations has established a permanent and expanding role for chemotherapy in the treatment of human malignancy.

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  1. B. A. Chabner
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  2. V. T. Oliverio
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  1. Laboratory of Chemical Pharmacology, National Heart and Lung Institute, National Institutes of Health, Bethesda, Maryland, 20014, USA

    James R. Gillette  & Jerry R. Mitchell  & 

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Chabner, B.A., Oliverio, V.T. (1975). Drug Interactions in Cancer Chemotherapy. In: Gillette, J.R., Mitchell, J.R. (eds) Concepts in Biochemical Pharmacology. Handbuch der experimentellen Pharmakologie / Handbook of Experimental Pharmacology, vol 28 / 3. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-46314-3_13

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