This study was designed to assess the capacity of etidronate disodium (etidronate) to affect neoplastic involvement of bone by murine tumors. Using sublines of the Walker 256 carcinoma, differing in the pattern of bone involvement, etidronate was found to inhibit hypercalcemia caused by systemically acting humoral factors, to inhibit bone metastasis following inoculation of tumor cells into the abdominal aorta, and to reduce the invasion of bone adjacent to tumors. Etidronate was also found to prevent bone metastasis in syngeneic rat mammary carcinoma. Etidronate was found devoid of direct antineoplastic activity, whether administered intramuscularly, subcutaneously, or intravenously, in a series of murine tumors of different histologic varieties. At the same time, it was shown that etidronate did not modify the antineoplastic activity of any of the major chemotherapeutic agents used in these studies, nor did it demonstrate any degree of immunosuppression. The experimental models used for this study should prove useful in evaluating agents that may affect the various types of bone involvement seen in neoplastic disease. The drug's apparent lack of interference with the antineoplastic activity of standard cytotoxic agents and its lack of immunosuppressive activity suggest that it may be readily adaptable to combination chemotherapy regimens.
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