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Treatment of N-Nitrosobis(2-oxopropyl)amine-induced Pancreatic Cancer in Syrian Golden Hamsters with D-Trp-6-LH-RH and Somatostatin Analogue RC-160 Microcapsules¹

Endocrine, Polypeptide and Cancer Institute [A. V. S.], Veterans Administration Medical Center and Section of Experimental Medicine, Department of Medicine, Tulane University School of Medicine [A. Z., A. V. S.], New Orleans, Louisiana 70146

Antitumoral effects of the agonist of luteinizing hormone-releasing hormone (D-Trp-6-LH-RH) and the somatostatin analog RC-160 (D-Phe-Cys-Tyr-D-Trp-Lys-Val-Cys-Trp-NH₂) on chemically induced ductal pancreatic adenocarcinomas were studied. The tumors were induced in female Syrian golden hamsters by weekly s.c. injections of N-nitrosobis(2-oxopropyl)amine at a dose of 10 mg/kg b.w. for 6 weeks. 18 weeks after the last injection, the peptides in controlled-release microcapsule formulations were administered s.c. The animals received the following therapies: Group 1 (N = 15), vehicle only; Group 2 (N = 13), D-Trp-6-LH-RH microcapsules releasing 25 µg/day injected s.c. once a month; Group 3 (N = 14), RC-160 microcapsules, liberating 25 µg/day administered s.c. every 15 days; Group 4 (N = 14), the combination of D-Trp-6-LH-RH plus RC-160 microcapsules. The experiment was terminated on the 80th day when all hamsters in the control group were dead, but in the treated Groups 2, 3, and 4, we observed 71, 77, and 86% of survival rate, respectively. In addition to the prolongation of survival, the combination treatment resulted in a significant decrease in the tumorous pancreatic weight, increase in the body weight of the animals, reduction in ascites from 100 to 8.3% and regressive histological changes in 67% of the specimens. Our findings suggest that somatostatin analogues and D-Trp-6-LH-RH could be considered for the development of hormonal therapy for pancreatic cancer.

¹ This work was supported by National Institutes of Health Grant CA-40077 (to A. V. S.) and the Veterans Administration Research Service (to A. V. S.).

² To whom requests for reprints should be addressed at Veterans Administration Medical Center, Quadrant 7 F, 1601 Perdido Street, New Orleans, LA 70146.

Received 8/ 8/88. Revised 11/ 8/88. Accepted 1/ 3/89.