Facilitated metastatic distribution of the Walker 256 tumor in sprague‐dawley rats with hydrocortisone and/or cyclophosphamide

The strain of Walker 256 tumor studied metastasized readily and preferentially to the lungs. Cyclophosphamide or hydrocortisone significantly increases extrapulmonary metastasis formation when 'cytostatic' therapy is begun when the primary tumor has reached 2.0‐2.5 cm in size. Drug mortality excluded, survival in animals treated with cyclophosphamide decreases despite a temporary retardation of the primary tumor growth rate. This decreased survival correlates with an increase in the number of pulmonary metastases and more widespread organ distribution of metastases. It is hypothesized that suppression of the host immune response by an alkylating agent and/or hydrocortisone was the likely mechanism involved, although localization of tumor cells at sites of chemical inflammation and other mechanisms have not been excluded. These data provide ancillary evidence for the hypothesis that the immune mechanism controls, at least in part, the formation of metastasis from circulating and/ or dormant tumor cells, particularly in organs which are not sites of preferential metastasis.