Prevention of intravascular metastases of B16 murine melanoma: adjuvant chemotherapy with actinomycin D.

Actinomycin D was tested in an experimental preparation to determine its efficacy in the prevention of intravenous metastases. B16 melanoma cells were injected intravenously in syngeneic C57/BL6 mice. Two cell lines of the tumor, designated F1 and F10, with widely different metastatic potentials, were maintained in tissue culture and utilized for evaluation of pulmonary metastases. When actinomycin D was given intraperitoneally at doses of 0.05 and 0.075 mg/kg for 5 days, the number of pulmonary metastases was significantly decreased (P less than .001) in both the F1 and F10 cell lines. Although reduction did occur with a single dose, maximum reduction of pulmonary metastases was effected with a dose schedule administered over 5 days. Evaluation of a group of mice 2 and 3 wk after injection of tumor cells revealed that the effects of actinomycin D were not secondary to delay in tumor growth but did represent highly significant differences in numbers of metastatic lesions. It is concluded that in this experimental preparation actinomycin D, given in an adjuvant setting, can significantly reduce the number of pulmonary metastases. This study may have bearing on the design of adjuvant intraoperative and perioperative chemotherapy in order to destroy circulating tumor cells.