title: A Nonselective Cyclooxygenase Inhibitor Enhances the Activity of Vinblastine in a Naturally-Occurring Canine Model of Invasive Urothelial Carcinoma.
abstract: Background:Chemotherapy is expected to remain an important part of invasive urothelial carcinoma (UC) treatment. Strategies to enhance chemotherapy efficacy are needed.Objective:To determine the chemotherapy-enhancing effects of a nonselective cyclooxygenase (COX) inhibitor on vinblastine in a naturally-occurring canine model of invasive UC.Methods:With IACUC approval, privately-owned dogs with naturally-occurring histologically-diagnosed invasive UC, expected survival ≥6 weeks, and informed owner consent were randomly allocated to receive vinblastine (2.5 mg/m2intravenously every 2 weeks) plus piroxicam (0.3 mg/kg daily per os) or vinblastine alone (same dose) with the option to receive piroxicam alone when vinblastine failed. Scheduled evaluations included physical exam, standard laboratory analyses, thoracic radiography, abdominal ultrasonography, and standardized measurement of urinary tract tumors.Results:Dogs receiving vinblastine alone (n= 27) and vinblastine-piroxicam (n= 24) were similar in age, sex, breed, tumor stage, and grade. Remission occurred more frequently (P<  0.02) with vinblastine-piroxicam (58.3%) than with vinblastine alone (22.2%). The median progression free interval was 143 days with vinblastine alone and 199 days with the combination. Interestingly, the overall median survival time was significantly longer (P<  0.03) in dogs receiving vinblastine alone followed by piroxicam alone (n= 20, 531 days) than in dogs receiving the combination (299 days). Treatment was well tolerated in both arms.Conclusions:Piroxicam significantly enhanced the activity of vinblastine in dogs with UC where the cancer closely mimics the human condition, clearly justifying further study. The study suggest the potential importance of tracking COX inhibitor use in patients in clinical trials as COX inhibitors could affect treatment response.
authors.affiliation: Department of Veterinary Clinical Sciences, Purdue University, West Lafayette, IN, USA; Purdue University Center for Cancer Research, Purdue University, West Lafayette, IN, USA.
authors.forename: Deborah W
authors.initials: DW
authors.lastname: Knapp
authors.affiliation: Department of Comparative Pathobiology, Purdue University , West Lafayette, IN, USA.
authors.forename: Audrey
authors.initials: A
authors.lastname: Ruple-Czerniak
authors.affiliation: Department of Comparative Pathobiology, Purdue University , West Lafayette, IN, USA.
authors.forename: José A
authors.initials: JA
authors.lastname: Ramos-Vara
authors.affiliation: Indiana Veterinary Imaging, Indianapolis, IN, USA.
authors.forename: James F
authors.initials: JF
authors.lastname: Naughton
authors.affiliation: Department of Veterinary Clinical Sciences, Purdue University , West Lafayette, IN, USA.
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Fulkerson
authors.affiliation: Department of Veterinary Clinical Sciences, Purdue University , West Lafayette, IN, USA.
authors.forename: Sonia I
authors.initials: SI
authors.lastname: Honkisz
keywords: Urinary bladder cancer; animal models; cyclooxygenase inhibitor; dog; piroxicam; transitional cell carcinoma; urothelial carcinoma; vinblastine