A phase I trial of the bombesin/gastrin-releasing peptide (BN/GRP) antagonist RC3095 in patients with advanced solid malignancies

Investigational New Drugs
Gilberto SchwartsmannG De Nucci

Abstract

Bombesin/gastrin-releasing peptides (BN/GRP) were shown to bind selectively to cell surface receptors, stimulating the growth of various types of malignancies in murine and human models. The novel BN/GRP synthetic receptor antagonist, RC-3095, was able to produce long-lasting tumor regressions in murine and human tumor models in vitro and in vivo. Animal toxicology studies showed no detectable organ toxicity apart from local irritation at the injection site. The purpose of this study was to determine the safety and feasibility of the administration of RC-3095 by daily subcutaneous injections in patients with advanced and refractory solid malignancies. Twenty-five patients received RC-3095 once or twice-daily at doses ranging from 8 to 96 ug/kg. Dose was escalated in groups of 3-5 patients per dose level. The only toxicity observed was local discomfort in the injection site at the highest doses. A single dose administration of RC-3095 at the highest dose level (96 ug/kg) was tested in a clearly hypergastrinemic individual with the Zollingen-Ellison syndrome and produced a decrease in plasma gastrin down to 50% of basal levels in 6 h. There was no objective tumor responses in patients included in the study. A short-lasting minor ...Continue Reading

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Citations

Nov 28, 2006·Nature Reviews. Cancer·Susan A WatsonArjun Takhar
Jun 26, 2013·Nature Reviews. Urology·Rafael Roesler, Gilberto Schwartsmann
Dec 29, 2011·Proceedings of the National Academy of Sciences of the United States of America·Rafael Sanguinetti CzepielewskiCristina Bonorino
Jan 11, 2008·Current Opinion in Endocrinology, Diabetes, and Obesity·Nieves GonzalezRobert T Jensen
Jan 1, 2014·Archives of Pathology & Laboratory Medicine·Jane MatteiGilberto Schwartsmann
May 31, 2014·World Journal of Gastroenterology : WJG·Florian HohlaAndrew V Schally
Nov 7, 2009·Digestive Diseases and Sciences·Daniel C DaminGilberto Schwartsmann
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Apr 16, 2013·Clinical and Experimental Dermatology·B F MarroneG Schwartsmann
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Sep 5, 2013·Neurobiology of Learning and Memory·Rafael RoeslerZul Merali
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Jan 11, 2008·Current Opinion in Endocrinology, Diabetes, and Obesity

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