A phase II study of vinblastine in combination with acrivastine in patients with advanced renal cell carcinoma.
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 resistance. After five patients were treated on a dose-finding study, seventeen 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 every 4 hours for 6 days and a 96-hour continuous infusion of vinblastine at a dose of 1.6 mg/m2/24 h. Of 15 evaluable patients, no tumor responses were seen. The regimen was well-tolerated with the majority of toxicities being gastrointestinal and hematologic. Serum levels of acrivastine, its principal metabolite (270C81) and vinblastine were measured during the study. Based on in vitro data, the plasma levels of acrivastine were within a range adequate to block P-glycoprotein activity. High doses of acrivastine were well-tolerated clinically, however, the combination of acrivastine and vinblastine was not active against renal cell carcinoma.
Berlin
J
J
Department of Human Oncology, University of Wisconsin Comprehensive Cancer, Madison.
King
A C
AC
Tutsch
K
K
Findlay
J W
JW
Kohler
P
P
Collier
M
M
Clendeninn
N J
NJ
Wilding
G
G
D000328:Adult; D000368:Aged; D002292:Carcinoma, Renal Cell / Q000188:drug therapy*; D018432:Drug Resistance, Multiple; D005260:Female; D006634:Histamine H1 Antagonists / Q000627:therapeutic use*; D006801:Humans; D007680:Kidney Neoplasms / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D014311:Triprolidine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D014747:Vinblastine / Q000627:therapeutic use*
D006634:Histamine H1 Antagonists; D014311:Triprolidine; D014747:Vinblastine; C043648:acrivastine