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The DLT for the simultaneous combination was neutropenia and the maximally tolerated dose was vinblastine (1.6 mg m<jats:sup>\u22122<\/jats:sup>every other week) concurrent with toceranib (3.25 mg kg<jats:sup>\u22121<\/jats:sup>PO, every other day). This represents greater than a 50% reduction in dose intensity for vinblastine (compared with single\u2010agent 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\u2010agent treatments would seem prudent to interrogate this potential.<\/jats:p>","DOI":"10.1111\/j.1476-5829.2011.00261.x","type":"journal-article","created":{"date-parts":[[2011,1,31]],"date-time":"2011-01-31T09:33:34Z","timestamp":1296466414000},"page":"174-183","source":"Crossref","is-referenced-by-count":42,"title":["Safety evaluation of combination vinblastine and toceranib phosphate (Palladia\u00ae) in dogs: a phase I dose\u2010finding study"],"prefix":"10.1111","volume":"10","author":[{"given":"C.","family":"Robat","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C.","family":"London","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L.","family":"Bunting","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L.","family":"McCartan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"N.","family":"Stingle","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K.","family":"Selting","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"I.","family":"Kurzman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D. 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