title: Safety evaluation of combination CCNU and continuous toceranib phosphate (Palladia(®) ) in tumour-bearing dogs: a phase I dose-finding study.
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.
authors.affiliation: School of Veterinary Medicine and the Carbone Cancer Center, University of Wisconsin-Madison, Madison, WI, USA.
authors.forename: X
authors.initials: X
authors.lastname: Pan
authors.affiliation: School of Veterinary Medicine and the Carbone Cancer Center, University of Wisconsin-Madison, Madison, WI, USA.
authors.forename: K
authors.initials: K
authors.lastname: Tsimbas
authors.affiliation: School of Veterinary Medicine and the Carbone Cancer Center, University of Wisconsin-Madison, Madison, WI, USA.
authors.forename: I D
authors.initials: ID
authors.lastname: Kurzman
authors.affiliation: School of Veterinary Medicine and the Carbone Cancer Center, University of Wisconsin-Madison, Madison, WI, USA.
authors.forename: D M
authors.initials: DM
authors.lastname: Vail
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D004283:Dog Diseases / Q000188:drug therapy*; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D007211:Indoles / Q000008:administration & dosage / Q000627:therapeutic use*; D008130:Lomustine / Q000008:administration & dosage / Q000627:therapeutic use*; D009369:Neoplasms / Q000188:drug therapy / Q000662:veterinary*; D011758:Pyrroles / Q000008:administration & dosage / Q000627:therapeutic use*
chemical_list: D000970:Antineoplastic Agents; D004338:Drug Combinations; D007211:Indoles; D011758:Pyrroles; C464577:toceranib phosphate; D008130:Lomustine
keywords: CCNU; canine; chemotherapy; toceranib; tyrosine kinase