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Vet Comp Oncol. 2012 Sep;10(3):174-83. doi: 10.1111/j.1476-5829.2011.00261.x. Epub 2011 Jan 31.

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

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School of Veterinary Medicine, University of Wisconsin-Madison, Madison, WI, USA.


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.

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