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Combination of N-Methylformamide with cis-Diamminedichloroplatinum(II) in Murine Mammary Carcinoma: Importance of Timing¹

Department of Experimental Radiotherapy, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030

The maturational agent N-methylformamide (NMF) is an antitumor agent that also enhances the response of tumor cells in vitro to chemotherapeutic agents. Here, we tested whether NMF can improve therapy of the murine MCA-K mammary carcinoma with cis-diamminedichloroplatinum(II) (cis-DDP). Although the in vitro cell cultures of MCA-K tumor cells exhibited increased sensitivity to cis-DDP cytotoxicity when they were first treated with NMF, administration of NMF to mice bearing MCA-K tumors did not enhance cis-DDP-induced tumor growth delay. However, when NMF treatment was begun after cis-DDP administration, the growth delays were significantly greater than those induced by the individual treatment, with an increase in temporary tumor regression and a small proportion of cures. These results indicate that therapeutic benefit can be achieved in this experimental tumor system when NMF is administered after cis-DDP. In addition, they demonstrate the significance of the timing of administration in combined protocols involving NMF.

¹ This investigation was supported in part by Research Grant CA-06294, awarded by the National Cancer Institute. Animals used in this study were maintained in facilities approved by the American Association for Accreditation of Laboratory Animal Care and in accordance with current regulations and standards of the United States Department of Agriculture and Department of Health and Human Services.

² Present address: Department of Pediatric Surgery, Chiba University, 8-1, Inohana-1-chome, Chiba-shi, Japan.

³ To whom requests for reprints should be addressed, at The University of Texas M. D. Anderson Cancer Center, Experimental Radiotherapy, 1515 Holcombe Blvd., Houston, TX 77030.

Received 4/22/88. Revised 12/12/88. Accepted 1/ 5/89.