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Adriamycin and Cyclophosphamide in Combination Chemotherapy of L1210 Leukemia¹

Laboratories of Pharmacology, St. Jude Children's Research Hospital, Memphis, Tennessee 38101

Combinations of cyclophosphamide and adriamycin, encompassing a wide range of dosages, were administered on five different schedules to C57BL/6J x DBA/2J F₁ female mice inoculated i.p. with L1210 ascites tumor cells. Among the resulting 85 treatment groups, the mean postinoculation survival of mice that died with tumor was 11.4 to 51.3 days; this represented increases of 62 to 628% over the survival of untreated controls. In some groups, tumor cells were eradicated in 9 of 10 treated mice. By contrast, neither drug given alone cured leukemic mice or extended their survival beyond controls by more than 96%. Adriamycin and cyclophosphamide were most effective when administered simultaneously on Day 1; additional treatment with adriamycin on Days 4 and 7 produced a significant increase in the survival of mice that died with tumor, but this regimen did not increase the incidence of cures. Combination therapy with these agents reduced the cytotoxic response of the host to subsequently inoculated L1210 cells. The pronounced therapeutic effectiveness of this drug combination is attributed to a true potentiation of the independent oncolytic action of each agent.

¹ Supported by Childhood Cancer Research Center Grant CA-08480 and Research Project Grant CA-12732, both from the National Cancer Institute, NIH, and by ALSAC.

² To whom requests for reprints should be addressed, at St. Jude Children's Research Hospital, P. O. Box 318, Memphis, Tenn. 38101.

Received 8/18/75. Accepted 12/ 3/76.