A PHASE-II STUDY OF VINBLASTINE IN COMBINATION WITH ACRIVASTINE IN PATIENTS WITH ADVANCED RENAL-CELL CARCINOMA

Citation
J. Berlin et al., A PHASE-II STUDY OF VINBLASTINE IN COMBINATION WITH ACRIVASTINE IN PATIENTS WITH ADVANCED RENAL-CELL CARCINOMA, Investigational new drugs, 12(2), 1994, pp. 137-141
Citations number
17
Categorie Soggetti
Pharmacology & Pharmacy",Oncology
Journal title
ISSN journal
01676997
Volume
12
Issue
2
Year of publication
1994
Pages
137 - 141
Database
ISI
SICI code
0167-6997(1994)12:2<137:APSOVI>2.0.ZU;2-1
Abstract
Renal cell carcinoma exhibits chemoresistance attributable in part to the P-glycoprotein drug efflux mechanism. Acrivastine is a hydrophylic antihistamine that has been shown in vitro to reverse this form of re sistance. After five patients were treated on a dose-finding study, se venteen patients with metastatic or unresectable renal cell carcinoma were entered into a phase II study of vinblastine in combination with acrivastine. Patients received oral acrivastine at doses of 400 mg eve ry 4 hours for 6 days and a 96-hour continuous infusion of vinblastine at a dose of 1.6 mg/m(2)/24 h. Of 15 evaluable patients, no tumor res ponses were seen. The regimen was well-tolerated with the majority of toxicities being gastrointestinal and hematologic. Serum levels of acr ivastine, its principal metabolite (270C81) and vinblastine were measu red during the study. Based on in vitro data, the plasma levels of acr ivastine were within a range adequate to block P-glycoprotein activity . High doses of acrivastine were well-tolerated clinically, however, t he combination of acrivastine and vinblastine was not active against r enal cell carcinoma.