INHIBITION OF THE GROWTH OF CAKI-I HUMAN RENAL ADENOCARCINOMA IN-VIVOBY LUTEINIZING-HORMONE-RELEASING HORMONE ANTAGONIST CETRORELIX, SOMATOSTATIN ANALOG RC-160, AND BOMBESIN ANTAGONIST RC-3940-II

BACKGROUND. Metastatic or recurrent renal cell carcinoma (RCC) is a th erapeutic challenge because it is resistant to chemotherapy and extern al radiotherapy. No uniformly effective therapeutic agents are availab le for the management of patients with RCC. Hormones and growth factor s may play a role in promoting the transformation and/or proliferation of kidney neoplasms. METHODS. Luteinizing hormone-releasing hormone ( LH-RH) antagonist Cetrorelix (SB-75), somatostatin analog RC-160, and bombesin antagonist RC-3940-II were tested for their effects on the gr owth of the Caki-I renal adenocarcinoma cell line xenografted into nud e mice. RESULTS. After 4 weeks of treatment, tumor volume was signific antly (P < 0.01) decreased in animals receiving RC-160, to 167.5 +/- 3 4.2 mm(3), compared with the control group (485.7 +/- 77.2 mm(3)). LH- RH antagonist SB-75 and bombesin antagonist RC-3940-II also significan tly reduced the volume of Caki-I tumors, to 159.9 +/- 18.1 and 234.7 /- 81.8 mm(3), respectively. Somatostatin analog RC-160 decreased seru m levels for growth hormone (GH) and insulin-like growth factor-I comp ared with controls. Treatment with RC-160, Cetrorelix, and RC-3940-II significantly reduced the number of high-affinity receptors for epider mal growth factor on Caki-I tumors. CONCLUSIONS. LH-RH antagonist Cetr orelix, somatostatin analog RC-160, and bombesin antagonist RC-3940-II effectively inhibit the growth of human Caki-I renal adenocarcinomas in nude mice. These peptide analogs should be considered for the thera py of patients with metastatic or recurrent RCC. (C) 1998 American Can cer Society.