Surgical adjuvant chemotherapy of metastatic murine tumors

Abstract

Surgery or radiation therapy fails to cure clinically evident cancer, in general, if the disease is systemic when first recognized, because neither modality can effectively remove or kill distant and/or unrecognized metastases. Drug treatment beginning at first clinical recognition fails to cure over 90% of cancers, systemic or not, because the body burden of tumor cells exceeds the tumor cell kill potential of most of our best drug treatments. The indicated approach to improving cure rates under these circumstances is combined-modality treatment. Surgical adjuvant chemotherapy of both osteogenic sarcoma and carcinoma of the breast has already been shown to increase the disease-free interval over that obtained with surgery alone, and the probability of having achieved significantly increased long-term cure rates is high. A number of transplantable metastatic murine tumors (lung, breast, colon, melanoma) which are uniformly fatal following subcutaneous implant have been studied at Southern Research Institute. The incidence of metastatic disease is directly related to tumor mass. Surgical cure rates drop as primary tumor mass at surgery increases. Grossly evident primary tumors are generally not curable by drug treatment. Surgical adjuvant chemotherapy has been shown reproducibly to increase the long-term cure rates of all of these tumors and increase the life span of curative failures significantly. Effective drug therapy in the surgical adjuvant setting is both dose-dependent and related to body burden of metastatic tumor at the time of drug treatment. Some drugs that are apparently ineffective against the presurgical total body burden of tumor cells are curative in some to all mice with metastatic disease if given shortly after surgical removal of the primary tumor. Examples of these several tumor systems and results of combined modality treatments are shown. Cancer 40:558–568, 1977.