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Treatment of R-3327 Prostate Tumors with a Somatostatin Analogue (Somatuline) as Adjuvant Therapy following Surgical Castration

Biomeasure Incorporated, Hopkinton, Massachusetts 01748 [A. E. B., J. E. T., J-P. M.] and Peptide Research Laboratories, Department of Medicine, Tulane University Medical Center, New Orleans, Louisiana 70112 [D. H. C.]

This study addresses, in an animal tumor model, the clinical problem of "escape from castration inhibition." Somatuline (BIM-23014C), an octapeptide analogue of somatostatin with enhanced potency and longer duration of biological activity was administered as a therapeutic agent, over a period of 90 and 197 days, to male Copenhagen rats bearing syngeneic Dunning R-3327-H prostate tumors. Androgen sensitivity was confirmed by the response of tumors to castration and by the significant inhibition of tumor growth in intact animals by treatment with a luteinizing hormone-releasing hormone antagonist (BIM-21009). Inhibition of tumor growth resulting from castration persisted for 102 days, after which progressive regrowth occurred, indicating an escape from castration inhibition. When Somatuline treatment was initiated as an adjuvant therapy 5 days after castration, the rate of tumor regrowth during escape was significantly retarded. During the period of 197 days postcastration, tumors in the vehicle-treated, intact controls grew to an average diameter of 38.6 ± 7.6 mm and tumors in vehicle-treated castrate controls grew to an average diameter of 23.3 ± 4.1 mm (60% test/control). Treatment with the luteinizing hormone-releasing hormone antagonist induced no significant additional tumor inhibitory effects in castrated animals which developed tumors having an average diameter of 30.2 ± 8.2 mm (78% test/control). Treatment of tumors in castrate animals with Somatuline, on the other hand, induced a significant (P < 0.01) tumor-inhibitory effect that was greater than that produced by castration alone, developing an average tumor diameter of only 14.3 ± 2.6 mm, (37% test/control). A growth inhibitory effect was also inducible in animals having tumors that had already escaped castration inhibition. The relative nontoxicity of a somatostatin analogue such as Somatuline suggests that chronic or maintenance therapy of slow-growing prostate cancers may be both feasible and acceptable in a clinical setting.

¹ To whom requests for reprints should be addressed, at Biomeasure Inc., 9–15 Avenue E, Hopkinton, MA 01748.

Received 6/19/89. Revised 1/16/90.

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