Safety evaluation of combination vinblastine and toceranib phosphate (Palladia®) in dogs: A phase I dose-finding study

C. Robat, C. London, L. Bunting, L. Mccartan, N. Stingle, K. Selting, I. Kurzman, D. M. Vail

Research output: Contribution to journalArticlepeer-review

Abstract

Combining drugs with known single-agent activity that lack overlapping dose-limiting toxicities (DLT) and exert antitumour activity through different mechanisms could improve clinical outcome. As toceranib and vinblastine meet these requisites, a phase I trial was performed in combination in dogs with mast cell tumours. The DLT for the simultaneous combination was neutropenia and the maximally tolerated dose was vinblastine (1.6 mg m-2 every other week) concurrent with toceranib (3.25 mg kg-1 PO, every other day). This represents greater than a 50% reduction in dose intensity for vinblastine (compared with single-agent use) and as such does not support this combination based on current drug combination paradigms. Although a strict adherence to dose paradigms speaks against the combination, evidence of significant activity (71% objective response) and enhanced myelosuppression suggest additive or synergistic activity. A prospective randomized evaluation comparing this combination with standard single-agent treatments would seem prudent to interrogate this potential.

Original languageEnglish (US)
Pages (from-to)174-183
Number of pages10
JournalVeterinary and comparative oncology
Volume10
Issue number3
DOIs
StatePublished - Sep 2012
Externally publishedYes

Keywords

  • Canine
  • Chemotherapy
  • Mast cell tumors
  • Oncology
  • Tyrosine kinase

ASJC Scopus subject areas

  • veterinary(all)

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