Pyrazomycin (PM) completely inhibited the growth of Walker carcinosarcoma 256. Mammary carcinoma 755, Gardner lymphosarcoma, and X5563 plasma cell myeloma were inhibited more than 50% by PM. Tumors that showed more than a minimum response of 30% were the C3H and 115 mammary carcinomas, Mecca lymphosarcoma, Taper liver tumor, and Ridgeway osteogenic sarcoma. The S91 melanoma, Sarcoma 180 ascites tumors, and Ehrlich ascites solid tumor showed no significant biological responses. PM also caused several well-established dimethyl-benzanthracene-induced mammary carcinomas to regress completely. The majority of the dimethylbenzanthracene-induced tumors in the treated rats regressed to some degree while most of the control tumors increased in size. The murine leukemias L1210, C1498, P1534, AKR, P388, or B82 showed no response to PM. Although PM did not inhibit the Ehrlich or Sarcoma 180 ascites tumors in mice, PM did cause up to 90% prolongation of life in rats with the Walker carcinosarcoma 256 ascites, and 9 of the 30 rats survived more than 45 days.
PM showed comparable activity against either Walker carcinosarcoma 256 or Gardner lymphosarcoma when given p.o., i.p., i.v., or i.m. It also showed comparable activity against Walker carcinosarcoma 256 when given once every 2, 3, 4, or 5 days. Plasma levels of PM-like activity were detected 3 days after a single p.o. dose of PM at 10 mg/kg in rats.
Presented in part at the 63rd Annual Meeting of the American Association of Cancer Research, Boston, Mass., May 1972 (7).