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The Antileukemic Effectiveness of 5-Fluorouracil and Methotrexate in the Combination Chemotherapy of Advanced Leukemia L1210 in Mice¹

Microbiological Associates, Inc., and Drug Evaluation Branch, Cancer Chemotherapy National Service Center, National Cancer Institute, Bethesda, Maryland

Enchanced therapeutic effectiveness has been demonstrated by combining methotrexate and 5-fluorouracil in the treatment of murine leukemia L1210. Optimal combinations of the 2 drugs consistently showed greater antileukemic activity than optimal treatment with each drug by itself. The treatment schedules resulting in this enhanced activity were characterized by relatively low and therapeutically ineffective doses of 5-fluorouracil, whereas the associated level of methotrexate ranged from slightly less than optimal to optimal. The therapeutic activity of the combination of the drugs was limited by the development of host toxicity similar to that observed when the drugs were used by themselves.

¹ This study was supported by Contract PH-43-64-911 from the Cancer Chemotherapy National Service Center, National Cancer Institute, NIH, USPHS. Presented (18) in part at the 55th Annual Meeting of the American Association for Cancer Research, April, 1964.

Received 8/27/65. Revised 11/ 8/65.

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