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Combination Chemotherapy of Sarcoma 180 with Methotrexate and Bleomycin¹

Department of Medicine, Yale University School of Medicine, New Haven, Connecticut 06510

Bleomycin (BLM) and methotrexate are each effective in the treatment of human squamous cell tumors and have different host toxicities. The murine ascites tumor Sarcoma 180, which is also sensitive to each of the drugs alone, was used as a model to see whether a combination of the drugs might be used with therapeutic advantage. Daily treatment with BLM and methotrexate resulted in significant toxicity and little additive therapeutic effect. Sequential treatment with BLM given on Days 1 to 5 and methotrexate given on Days 8 and 9 yielded median survivals no better than those with BLM alone. Treatment with single doses of each drug simultaneously on Day 1 or 2 after inoculation resulted in median survivals that were greater than what would be expected if the effects were additive. Simultaneous treatment was better than when either drug preceded the other by 12 to 24 hr. The results suggest that the clinical trials of the combination would be worthwhile and that simultaneous treatment with each drug would be the preferred schedule for treatment.

¹ Supported in part by USPHS Grant CA 08341.

Received 11/22/72. Accepted 2/ 5/73.