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Antitumor Activity of Macromomycin B (NSC 170105) against Murine Leukemias, Melanoma, and Lung Carcinoma¹

Drug Evaluation Branch, National Cancer Institute, Bethesda, Maryland [M. M. L., B. J. A., J. V., M. B.], and Southern Research Institute, Birmingham, Alabama 35205 [W. R. L.]

Mice bearing either of the two rapidly growing mouse leukemias, L1210 or P388, or the slow-growing B16 melanoma responded to i.p. injections of Macromomycin B (NSC 170105) with significant increases in life-span. The maximal increases in life-span obtained in these experiments were 37% for L1210, 68% for P388, and 120% for B16. In addition, there were 7 of 30 cures for varying doses of Macromomycin in the B16 melanoma. Activity of over 50% increase in life-span in B16 was obtained with a daily i.p. injection on Days 1 to 9 of 16 to 40 mg/kg. Animals that had received s.c. implanted Lewis lung tumors responded to either single or repeated injections (8 to 16 mg/kg) given at the site of tumor implant by a marked reduction in growth of the primary tumor, increased life-span, and some cures. The same doses were without effect when administered i.p. The reported activity of Macromomycin against L1210, P388 leukemias, B16 melanoma, and Lewis lung carcinoma make it a good candidate for development for clinical trial against human solid tumors.

A new method of evaluating activity against solid tumors, "responder analysis," is also presented.

¹ Studies on B16 melanoma were carried out under contracts to Southern Research Institute (1-CN-12098), Hazelton (1-CN-23704), and Arthur D. Little (1-CN-33727) from Division of Cancer Treatment, National Cancer Institute, NIH, Department of Health, Education and Welfare, under the expert supervision of W. R. Laster, L. Dudeck, and I. Wodinsky, respectively.

Received 2/27/74. Accepted 12/26/74.