Randomized Trial of Cisplatin versus Firocoxib versus Cisplatin/Firocoxib in Dogs with Transitional Cell Carcinoma of the Urinary Bladder

Journal of Veterinary Internal Medicine

D.W. Knapp²  C.J. Henry⁶  W.R. Widmer⁷  K.M. Tan⁵  G.E. Moore³  J.A. Ramos-Vara³  M.D. Lucroy¹  C.B. Greenberg⁷  S.N. Greene⁷  A.H. Abbo⁷  P.D. Hanson⁴  R. Alva⁴ 

[1] Elanco Animal Health, Greenfield, IN;Purdue University Center for Cancer Research, Purdue University, West Lafayette, IN;Department of Comparative Pathobiology, Purdue University, West Lafayette, IN;Merial Limited, Duluth, GA;Department of Statistics;Department of Veterinary Medicine and Surgery, College of Veterinary Medicine;Department of Veterinary Clinical Sciences

关键词: Bladder cancer;    Canine;    Chemotherapy;    Cox inhibitor;    Oncology;   

DOI  :  10.1111/jvim.12013

来源: Wiley

【 摘 要 】

Abstract

Background

Cisplatin combined with a nonselective cyclooxygenase (cox) inhibitor has potent antitumor activity against transitional cell carcinoma (TCC) in dogs, but this treatment is limited by renal toxicosis. Cox-2 is expressed in TCC, but only in limited sites within the kidney. A cox-2 inhibitor could enhance the antitumor activity of cisplatin with potentially fewer adverse effects on the kidney.

Hypothesis

Cisplatin/cox-2 inhibitor treatment will have greater antitumor activity but no more renal toxicosis than cisplatin alone in dogs with TCC.

Animals

Forty-four dogs with naturally occurring urinary bladder TCC.

Methods

Dogs were randomized to receive cisplatin (60 mg/m² IV q21d), firocoxib (5 mg/kg PO q24h), or the combination. Tumor measurements were determined before and at 6-week intervals during treatment. Renal function was monitored by serum creatinine concentration, iohexol clearance, and urine specific gravity. Toxicoses were graded according to Veterinary Co-Operative Oncology Group (VCOG) criteria.

Results

The remission rate with cisplatin/firocoxib (57%) was significantly (P = .021) higher than that with cisplatin alone (13%). Renal and gastrointestinal toxicoses were common in dogs receiving cisplatin, but there were no significant differences between dogs receiving cisplatin or cisplatin/firocoxib. Firocoxib alone induced partial remission or stable disease in 20 and 33% of dogs, respectively.

Conclusions

Firocoxib significantly enhanced the antitumor activity of cisplatin resulting in partial remission in more than half of the cases. The toxicoses inherent to cisplatin, however, were noted in dogs receiving this combination. Firocoxib had antitumor effects as a single agent and can be considered a palliative treatment for dogs with TCC.

【 授权许可】

Unknown   
Copyright © 2012 by the American College of Veterinary Internal Medicine