Pulse‐Administered Toceranib Phosphate Plus Lomustine for Treatment of Unresectable Mast Cell Tumors in Dogs

Journal of Veterinary Internal Medicine

J.H. Burton²  R.O. Venable²  D.M. Vail⁴  L.E. Williams⁶  C.A. Clifford³  S.M. Axiak-Bechtel⁵  A.C. Avery¹ 

[1] Flint Animal Cancer Center, Department of Microbiology, Immunology and Pathology, Colorado State University, Fort Collins, CO;Flint Animal Cancer Center, Department of Clinical Sciences, Colorado State University, Fort Collins, CO;Red Bank Veterinary Hospital, Tinton Falls, NJ;School of Veterinary Medicine and the Carbone Cancer Center, University of Wisconsin-Madison, Madison, WI;Department of Veterinary Medicine and Surgery, University of Missouri, Columbia, MO;Department of Clinical Sciences, North Carolina State University, Raleigh, NC

关键词: Cancer;    Chemotherapy;    Dog;    Tyrosine kinase inhibitor;   

DOI  :  10.1111/jvim.13573

来源: Wiley

【 摘 要 】

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.

Hypothesis/Objectives

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.

Animals

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/m². All dogs were concurrently treated with diphenhydramine, omeprazole, and prednisone.

Results

The MTD of lomustine was established at 50 mg/m² 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 and clinical importance

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.

【 授权许可】

CC BY-NC   
Copyright © 2015 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

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