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Antitumor Efficacy of Interleukin-2 Alone and in Combination with Adriamycin and Dacarbazine in Murine Solid Tumor Systems¹

Department of Internal Medicine, Division of Hematology and Oncology, Wayne State University School of Medicine, Detroit, Michigan 48202-0188 [P. M. L., L. P., B. G. R., M. V., T. H. C.]; Cetus Corporation, 1400 33rd Street, Emeryville, California 94608 [S. L. A.]; and Department of Internal Medicine, Wayne State University School of Medicine, Detroit, Michigan 48202-0188 [L. B.]

Recombinant interleukin-2 (IL-2)/chemotherapy combinations have recently entered clinical trial. The rationale for sequencing has primarily been empiric or based on in vitro data. To establish in vivo models for chemoimmunotherapy trials, we investigated IL-2 alone and in combination with dacarbazine (DTIC) and adriamycin. IL-2 (as a single agent given i.v. at 1–3 x 10⁵ Cetus units once daily for 5 days, repeated 7–10 days later), was highly active against an immunogenic line of colon adenocarcinoma no. 11/A [tumor growth inhibition (T/C) = 0% with cures]. It was modestly active against colon adenocarcinoma no. 38 (T/C = 39%), mammary adenocarcinoma no. 16/C (T/C = 18%), and B₁₆ melanoma (T/C = 21%). IL-2 was inactive against colon adenocarcinoma no. 7/A (T/C = 83%). Combination trials were done using DTIC and IL-2 against colon no. 7/A and upstaged colon no. 11/A. The combination of adriamycin and IL-2 was tested against mammary adenocarcinoma no. 16/C. In the DTIC/IL-2 combination trials, the combination was superior over either agent used alone. In the Il-2/adriamycin trials, the combination was no better than adriamycin alone at optimum dosages.

¹ This work was supported by Cetus Corporation, National Institutes of Health Grant CA-45962, and the Ben Kasle Trust Fund for Cancer Research.

² To whom requests for reprints should be addressed, at Harper Hospital, Division of Hematology and Oncology, P.O. Box 02188, Detroit, MI 48202-0188.

Received 8/21/89. Accepted 6/19/90.

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