title: Pulse-Administered Toceranib Phosphate Plus Lomustine for Treatment of Unresectable Mast Cell Tumors in Dogs.
abstract: BACKGROUND
  Nonresectable mast cell tumors (MCT) in dogs remain a therapeutic challenge, and investigation of novel combination therapies is warranted. Intermittent administration of tyrosine kinase inhibitors (TKI) combined with cytotoxic chemotherapy may effectively chemosensitize canine MCT while decreasing cost and adverse effects associated with either agent administered as monotherapy.
  
  
  OBJECTIVE
  The primary study objectives were to (1) identify the maximally tolerated dose (MTD), (2) determine the objective response rate (ORR) and (3) describe the adverse event profile of pulse-administered toceranib phosphate (TOC) combined with lomustine.
  
  
  METHODS
  Forty-seven client-owned dogs with measurable MCT.
  
  
  METHODS
  Toceranib phosphate was given PO on days 1, 3 and 5 of a 21-day cycle at a target dosage of 2.75 mg/kg. Lomustine was given PO on day 3 of each cycle at a starting dosage of 50 mg/m(2) . All dogs were concurrently treated with diphenhydramine, omeprazole, and prednisone.
  
  
  RESULTS
  The MTD of lomustine was established at 50 mg/m(2) when combined with pulse-administered TOC; the dose-limiting toxicity was neutropenia. Forty-one dogs treated at the MTD were evaluable for outcome assessment. The ORR was 46% (4 complete response, 15 partial response) and the overall median progression-free survival (PFS) was 53 days (1 to >752 days). On multivariate analysis, variables significantly associated with improved PFS included response to treatment, absence of metastasis, and no previous chemotherapy.
  
  
  CONCLUSIONS
  Combined treatment with pulse-administered TOC and lomustine generally is well tolerated and may be a reasonable treatment option for dogs with unresectable or metastatic MCT.
authors.affiliation: Flint Animal Cancer Center, Department of Clinical Sciences, Colorado State University, Fort Collins, CO.|Department of Surgical and Radiological Sciences, University of California, Davis, Davis, CA.
authors.forename: J H
authors.initials: JH
authors.lastname: Burton
authors.affiliation: Flint Animal Cancer Center, Department of Clinical Sciences, Colorado State University, Fort Collins, CO.|Arizona Veterinary Oncology, Gilbert, AZ.
authors.forename: R O
authors.initials: RO
authors.lastname: Venable
authors.affiliation: School of Veterinary Medicine and the Carbone Cancer Center, University of Wisconsin-Madison, Madison, WI.
authors.forename: D M
authors.initials: DM
authors.lastname: Vail
authors.affiliation: Department of Clinical Sciences, North Carolina State University, Raleigh, NC.|Veterinary Specialty Hospital of the Carolinas, Cary, NC.
authors.forename: L E
authors.initials: LE
authors.lastname: Williams
authors.affiliation: Red Bank Veterinary Hospital, Tinton Falls, NJ.|Hope Veterinary Specialists, Malvern, PA.
authors.forename: C A
authors.initials: CA
authors.lastname: Clifford
authors.affiliation: Department of Veterinary Medicine and Surgery, University of Missouri, Columbia, MO.
authors.forename: S M
authors.initials: SM
authors.lastname: Axiak-Bechtel
authors.affiliation: Flint Animal Cancer Center, Department of Microbiology, Immunology and Pathology, Colorado State University, Fort Collins, CO.
authors.forename: A C
authors.initials: AC
authors.lastname: Avery
authors.affiliation: Flint Animal Cancer Center, Department of Clinical Sciences, Colorado State University, Fort Collins, CO.
authors.forename: D H
authors.initials: DH
authors.lastname: Thamm
mesh_terms: D000818:Animals; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage / Q000627:therapeutic use*; D004283:Dog Diseases / Q000188:drug therapy* / Q000235:genetics; D004285:Dogs; D004334:Drug Administration Schedule / Q000662:veterinary; D004359:Drug Therapy, Combination; D005260:Female; D007211:Indoles / Q000008:administration & dosage / Q000627:therapeutic use*; D008130:Lomustine / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D008415:Mastocytosis / Q000188:drug therapy / Q000235:genetics / Q000662:veterinary*; D016133:Polymerase Chain Reaction / Q000662:veterinary; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics; D011758:Pyrroles / Q000008:administration & dosage / Q000627:therapeutic use*
chemical_list: D018906:Antineoplastic Agents, Alkylating; D007211:Indoles; D011758:Pyrroles; C464577:toceranib phosphate; D008130:Lomustine; D011505:Protein-Tyrosine Kinases; D019009:Proto-Oncogene Proteins c-kit
keywords: Cancer; Chemotherapy; Dog; Tyrosine kinase inhibitor