Phase I clinical trial and pharmacokinetics of intravesical mitomycin C in dogs with localized transitional cell carcinoma of the urinary bladder

A. H. Abbo, D. R. Jones, A. R. Masters, J. C. Stewart, L. Fourez, D. W. Knapp

Research output: Contribution to journalArticlepeer-review

21 Scopus citations

Abstract

Background: Transitional cell carcinoma (TCC) is the most common cancer of the urinary tract in dogs. The most frequent cause of death is urinary obstruction from the primary tumor. Standard medical therapy for TCC is only partially effective. Hypothesis/Objectives: Intravesical administration of mitomycin C (MMC) in dogs with invasive TCC will result in antitumor activity against the primary tumor and minimal systemic drug absorption. Animals: Thirteen privately owned dogs with naturally occurring, histopathologically diagnosed TCC of the urinary bladder. Methods: A prospective phase I trial was performed. MMC was given intravesically (600 mg/mL initial concentration) for 1 h/d for 2 consecutive days each month. The MMC concentration was escalated to a maximum of 800 mg/mL in groups of 3 dogs until the maximum tolerated dose (MTD) was determined. Serum assays for MMC were performed to determine the extent of systemic absorption of the MMC. Results: The MTD of MMC based on local toxicoses was 700 mg/mL (1-h dwell time, 2 consecutive days). In addition, 2 dogs had severe myelosuppression and appeared to have systemic absorption of MMC. Five dogs had partial remission, and 7 dogs had stable disease. Conclusions: IntravesicalMMChas antitumor activity in dogs with invasive TCC. Further study is needed to determine the cause of the myelosuppression associated with MMC administration, and to develop strategies to minimize this risk.

Original languageEnglish (US)
Pages (from-to)1124-1130
Number of pages7
JournalJournal of Veterinary Internal Medicine
Volume24
Issue number5
DOIs
StatePublished - Sep 2010

Keywords

  • Bladder cancer
  • Canine species
  • Dog species

ASJC Scopus subject areas

  • veterinary(all)

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