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Safety evaluation of combination CCNU and continuous toceranib phosphate (Palladia ® ) in tumour‐bearing dogs: a phase I dose‐finding study
Author(s) -
Pan X.,
Tsimbas K.,
Kurzman I. D.,
Vail D. M.
Publication year - 2016
Publication title -
veterinary and comparative oncology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.864
H-Index - 34
eISSN - 1476-5829
pISSN - 1476-5810
DOI - 10.1111/vco.12091
Subject(s) - phosphate , phase (matter) , chemistry , bearing (navigation) , pharmacology , medicine , biochemistry , computer science , organic chemistry , artificial intelligence
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.