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Beneficial Effects of Androgen-primed Chemotherapy in the Dunning R3327 G Model of Prostatic Cancer

Division of Endocrinology [H. F. E., S. L., R. J. S.], Division of Urology [H. F. E.], and Center for Biostatistics and Epidemiology [D. F. H.], The Pennsylvania State University School of Medicine, Hershey, Pennsylvania 17033

The objective of this study was to test the hypothesis that androgen administration prior to chemotherapy (androgen priming) may potentiate tumor cytotoxicity in hormone-responsive prostate cancer. Accordingly, six groups of Copenhagen rats bearing small (i.e., 40-mm³ median volume) Dunning R3327 G tumors were left untreated or received castration, chemotherapy, or a combination of the two, with or without androgen priming. Groups without priming included: intact untreated, castrate alone, intact plus chemotherapy, and castrate plus chemotherapy (cyclophosphamide, 30 mg/kg/day, for 2 days, with repeat cycle in 24 days) (Cx). To specifically evaluate the effect of androgen priming on Cx cytotoxicity, two additional castrate groups were studied. One received testosterone propionate (4 mg/kg/day) for 2 days prior to Cx and the other after Cx. Treatment effect was evaluated by quantitating tumor volume as well as animal survival to an ethically allowable, maximal tumor burden.

As expected, castration and Cx produced a retardation of tumor growth and prolongation of survival when compared to untreated animals. The addition of androgen priming prior to but not after Cx enhanced the degree of tumor suppression. Specifically, 26 days after the second Cx cycle, all androgen-primed tumors had regressed; 70% of tumors had disappeared and those remaining were barely palpable. At this same time point, tumors in all the other groups were actively growing and had volumes greater than initial values (P < 0.01). Although tumor regrowth occurred, median survival for the androgen-primed group was significantly prolonged, to 186 days versus 39 days (P < 0.01) for untreated animals and 153 days for the non-primed castrate plus Cx animals (P < 0.01). These data suggested that androgen priming potentiates the effects of Cx in castrate animals bearing R3327 G tumors.

¹ To whom requests for reprints should be addressed, at the Milton S. Hershey Medical Center, Department of Medicine/Endocrinology Division, P.O. Box 850, Hershey, PA 17033.

Received 8/30/90. Accepted 1/21/91.

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