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Modification of the Effect of a Gonadoliberin Analog on 7,12-Dimethylbenz(a)anthracene-induced Rat Mammary Tumors by Hormone Replacement¹

Division of Clinical Oncology, Wisconsin Clinical Cancer Center, University of Wisconsin, Madison, Wisconsin 53792

A gonadoliberin analog, (D-leucyl⁶, desglycyl-NH₂¹⁰, prolyl ethylamide⁹) gonadoliberin, is known to suppress ovarian function and plasma prolactin levels. Its antitumor activity was evaluated against mammary tumors induced in Sprague-Dawley rats by dimethylbenz(a)anthracene. Observations were made when the analog, referred to as A-43818, was given alone and together with estrogen replacement or perphenazine. A-43818, 10 µg s.c. twice a day for 6 weeks, was highly effective in producing tumor remissions. All of the 11 animals survived throughout the observation period, complete regressions occurred in 8 of 13 tumors, and 2 were classified as static. None of the 16 tumors in 12 control rats regressed, and there were 4 deaths. When estradiol benzoate, 2 µg s.c. each day, was administered with the A-43818, antitumor activity was suppressed; only 2 of 17 tumors regressed, 6 were static, and 5 of the 10 rats in this group died. Perphenazine, 1 mg i.m. daily, a dose known to cause hyperprolactinemia, also impaired the efficacy of A-43818. Three of 14 tumors regressed, 6 were static, and the rest continued to grow; 3 of the 12 rats died within 6 weeks of starting treatment.

¹ Supported in part by USPHS Grant CA 14520 awarded to the Wisconsin Clinical Cancer Center by the National Cancer Institute.

² To whom requests for reprints should be addressed.

Received 4/16/79. Accepted 7/10/79.