Thoughts on Cancer Chemotherapy and Combination Modality Therapy (1974)

Localized cancers, even very large, slowly growing, tumor cell masses, often are curable by surgery or irradiation. The major limitation to these modalities is widespread metastasis. Chemotherapy is the most effective means for treatment of widely disseminated cancer cells. The major limitations to chemotherapy are (1) permanently resistant variant tumor cells (eg, one in a million tumor cells resistant to a single drug or class of drugs) and (2) "resting tumor cell resistance" that is not inherent or necessarily permanent. Both of these types of resistance are most frequently encountered in relatively large, slowly growing, tumor cell masses. Combination modality treatment already has proved more effective than surgery alone, irradiation alone, or chemotherapy alone in a number of "disseminated" solid cancers in both animals and man. Data gained at the molecular, cellular, and in vivo levels point to the potential of combination modality therapy against additional metastatic cancers. (JAMA230:1033-1035, 1974)