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

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          Abstract

          While maintaining a standard toceranib dosage [2.75 mg kg(-1) , PO, every other day (EOD)], three dose-escalating CCNU cohorts up to and including 60 mg m(-2) , PO, q3wk, were completed. The dose-limiting toxicities (DLT) for the combination were neutropenia and the maximum tolerated dose (MTD) for CCNU when given with continuous toceranib was determined to be 50 mg m(-2) , q3wk. While activity is not a primary objective of phase I trials, we observed one complete (lymphoma) and four partial responses (lymphoma, sarcoma, undifferentiated carcinoma and prostatic carcinoma) and two dogs experienced stable disease for >6 weeks [gastric adenocarcinoma and metastatic multilobulated osteochondrosarcoma (MLO)] for an objective response rate of 38.4% and a biological response rate of 53.8%. Concurrent continuous toceranib (2.75 mg kg(-1) , EOD) and pulse dose CCNU (50 mg m(-2) , q3wk) was well tolerated. Phase II effectiveness and phase III prospective randomized trials should further interrogate the potential activity of this combination.

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          Author and article information

          Journal
          Vet Comp Oncol
          Veterinary and comparative oncology
          Wiley-Blackwell
          1476-5829
          1476-5810
          Jun 2016
          : 14
          : 2
          Affiliations
          [1 ] School of Veterinary Medicine and the Carbone Cancer Center, University of Wisconsin-Madison, Madison, WI, USA.
          Article
          10.1111/vco.12091
          24735385
          42363c35-e3b5-4c28-95d2-e2cea5b7e6a1
          History

          chemotherapy,canine,CCNU,tyrosine kinase,toceranib
          chemotherapy, canine, CCNU, tyrosine kinase, toceranib

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