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Investigational New Drugs

, Volume 12, Issue 2, pp 137–141 | Cite as

A phase II study of vinblastine in combination with acrivastine in patients with advanced renal cell carcinoma

  • Jordan Berlin
  • A. Christie King
  • Kendra Tutsch
  • John W. Findlay
  • Peter Kohler
  • Mary Collier
  • Neil J. Clendeninn
  • George Wilding
Phase II Studies

Summary

Renal cell carcinoma exhibits chemoresistance attributable in part to the P-glycoprotein drug efflux mechanism. Acrivastine is a hydrophylic antihistamine that has been shownin 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 onin 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.

Key words

renal cell carcinoma acrivastine vinblastine drug resistance P glycoprotein 

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Copyright information

© Kluwer Academic Publishers 1994

Authors and Affiliations

  • Jordan Berlin
    • 1
    • 3
  • A. Christie King
    • 3
    • 4
  • Kendra Tutsch
    • 1
    • 3
  • John W. Findlay
    • 3
    • 4
  • Peter Kohler
    • 1
    • 3
  • Mary Collier
    • 3
    • 4
  • Neil J. Clendeninn
    • 3
    • 4
  • George Wilding
    • 1
    • 2
  1. 1.Department of Human OncologyUniversity of Wisconsin Comprehensive CancerUSA
  2. 2.the William S. Middleton Veterans Administration HospitalMadison
  3. 3.Meriter Hospital/ParkMadison
  4. 4.Cancer Therapy DepartmentBurroughs Wellcome Co.Research Triangle ParkUSA

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