Release of daunorubicin from polymethylmethacrylate for the improvement of the local growth control of bone metastasis animal experiments.

Bone metastases are a sign of advanced tumor disease. Surgical therapy is only occasionally curative. Therefore, the therapeutic goals are a limited surgical excision, immediate mobilization, effective stabilization and the avoidance of local recurrence. We investigated the effect of the anthracycline daunorubicin (DNR) in conjunction with polymethylmethacrylate (PMMA) in vitro and in animal experiments for regional control of bone metastases. Previous experiments of local chemotherapy in bone metastases using methotrexate (MTX) were done by Langendorff and Hernigou. In our own experiments we improved the release of daunorubicin from polymethylmethacrylate in vitro and in vivo up to 90% by adding mannitol. In in vivo experiments we investigated the combination of DNR and PMMA in athymic nude mice and Wistar rats. Cells from human breast cancer, bronchial carcinoma, nephroma, and soft tissue sarcoma were subcutaneously implanted bilaterally under the dorsal skin of nude mice. After reaching a diameter of 0.5 cm, the tumors were marginally excised, leaving microscopic tumor residuum behind. The tumor cavities were either filled with PMMA or alternatively with DNR-PMMA. The goal was to avoid tumor recurrence in the DNR-PMMA filled resection cavities. The number of recurrences was significantly lower in the DNR-PMMA treated animals, except in the breast cancer group. Additionally we implanted a rat sarcoma intrafemorally into Wistar rats. After 17 days the tumor was marginally excised and the resection cavity was filled with either DNR-PMMA or PMMA alone. The therapeutic goal was to prevent local recurrence. Histological and pharmacological tests concerning toxicity and drug distribution within the body completed the study. We concluded that the addition of daunorubicin to PMMA supplements surgical resection. We were able to reduce the number of, or delay recurrences in our animal models. Systemic side effects could be minimized despite the achievement of high local drug concentrations.