Impact of Toceranib/Piroxicam/Cyclophosphamide Maintenance Therapy on Outcome of Dogs with Appendicular Osteosarcoma following Amputation and Carboplatin Chemotherapy: A Multi-Institutional Study.
BACKGROUND
We hypothesized that the addition of toceranib to metronomic cyclophosphamide/piroxicam therapy would significantly improve disease-free interval (DFI) and overall survival (OS) in dogs with appendicular osteosarcoma (OSA) following amputation and carboplatin chemotherapy.


RESULTS
This was a randomized, prospective clinical trial in which dogs with OSA free of gross metastatic disease (n = 126) received carboplatin chemotherapy (4 doses) following amputation. On study entry, dogs were randomized to receive piroxicam/cyclophosphamide with or without toceranib (n = 63 each) after completing chemotherapy. Patient demographics were not significantly different between both groups. During or immediately following carboplatin chemotherapy, 32 dogs (n = 13 toceranib; n = 19 control) developed metastatic disease, and 13 dogs left the study due to other medical conditions or owner preference. Following carboplatin chemotherapy, 81 dogs (n = 46 toceranib; n = 35 control) received the metronomic treatment; 35 dogs (n = 20 toceranib; n = 15 control) developed metastatic disease during the maintenance therapy, and 26 dogs left the study due to other medical conditions or owner preference. Nine toceranib-treated and 11 control dogs completed the study without evidence of metastatic disease 1-year following amputation. Toceranib-treated dogs experienced more episodes of diarrhea, neutropenia and weight loss than control dogs, although these toxicities were low-grade and typically resolved with supportive care. More toceranib-treated dogs (n = 8) were removed from the study for therapy-associated adverse events compared to control dogs (n = 1). The median DFI for control and toceranib treated dogs was 215 and 233 days, respectively (p = 0.274); the median OS for control and toceranib treated dogs was 242 and 318 days, respectively (p = 0.08). The one year survival rate for control dogs was 35% compared to 38% for dogs receiving toceranib.


CONCLUSIONS
The addition of toceranib to metronomic piroxicam/cyclophosphamide therapy following amputation and carboplatin chemotherapy did not improve median DFI, OS or the 1-year survival rate in dogs with OSA.
Departments of Veterinary Biosciences and Veterinary Clinical Sciences, College of Veterinary Medicine, The Ohio State University, Columbus, Ohio, United States of America.
Cheryl A
CA
London
Departments of Veterinary Biosciences and Veterinary Clinical Sciences, College of Veterinary Medicine, The Ohio State University, Columbus, Ohio, United States of America.
Heather L
HL
Gardner
Departments of Veterinary Biosciences and Veterinary Clinical Sciences, College of Veterinary Medicine, The Ohio State University, Columbus, Ohio, United States of America.
Tamra
T
Mathie
Departments of Veterinary Biosciences and Veterinary Clinical Sciences, College of Veterinary Medicine, The Ohio State University, Columbus, Ohio, United States of America.
Nicole
N
Stingle
Department of Veterinary Clinical Medicine, University of Illinois at Urbana-Champaign, College of Veterinary Medicine, Champaign, Illinois, United States of America.
Roberta
R
Portela
Division of Biostatistics, College of Public Health, The Ohio State University, Columbus, Ohio, United States of America.
Michael L
ML
Pennell
Hope Veterinary Specialists, Malvern, Pennsylvania, United States of America.
Craig A
CA
Clifford
Veterinary Cancer Group, Tustin, California, United States of America.
Mona P
MP
Rosenberg
Department of Medical Sciences, School of Veterinary Medicine, University of Wisconsin, Madison, Madison, Wisconsin, United States of America.
David M
DM
Vail
Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, North Carolina, United States of America.
Laurel E
LE
Williams
New England Veterinary Oncology Group, Waltham, Massachusetts, United States of America.
Kim L
KL
Cronin
Department of Small Animal Clinical Sciences, College of Veterinary Medicine, Texas A&M University, College Station, Texas, United States of America.
Heather
H
Wilson-Robles
Department of Veterinary Clinical Sciences, University of Minnesota College of Veterinary Medicine, St. Paul, Minnesota, United States of America.
Antonella
A
Borgatti
Department of Veterinary Medicine and Surgery, College of Veterinary Medicine, University of Missouri, Columbia, Missouri, United States of America.
Carolyn J
CJ
Henry
Oradell Animal Hospital, Paramus, New Jersey, United States of America.
Dennis B
DB
Bailey
Southeast Veterinary Oncology and Medicine, Orange Park, Florida, United States of America.
Jennifer
J
Locke
Department of Small Animal Medicine and Surgery, University of Georgia, College of Veterinary Medicine, Athens, Georgia, United States of America.
Nicole C
NC
Northrup
Sage Centers for Veterinary Specialty and Emergency Care, Concord, California, United States of America.
Martin
M
Crawford-Jakubiak
VCA Katonah Bedford Veterinary Center, Bedford Hill, New York, United States of America.
Virginia L
VL
Gill
Southwest Veterinary Oncology, Tucson, Arizona, United States of America.
Mary K
MK
Klein
Veterinary Specialty Hospital of the Carolinas, Cary, North Carolina, United States of America.
David M
DM
Ruslander
Department of Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, Colorado, United States of America.
Doug H
DH
Thamm
Veterinary Specialty Hospital of San Diego, San Diego, California, United States of America.
Brenda
B
Phillips
The Veterinary Cancer Center, Norwalk, Connecticut, United States of America.
Gerald
G
Post
D059250:Administration, Metronomic; D000671:Amputation, Surgical; D000818:Animals; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000662:veterinary; D016190:Carboplatin / Q000627:therapeutic use*; D003520:Cyclophosphamide / Q000008:administration & dosage*; D003967:Diarrhea / Q000209:etiology; D018572:Disease-Free Survival; D004283:Dog Diseases / Q000188:drug therapy; D004285:Dogs; D004359:Drug Therapy, Combination; D005260:Female; D007211:Indoles / Q000008:administration & dosage* / Q000009:adverse effects; D053208:Kaplan-Meier Estimate; D008297:Male; D009503:Neutropenia / Q000209:etiology; D012516:Osteosarcoma / Q000188:drug therapy* / Q000662:veterinary; D010894:Piroxicam / Q000008:administration & dosage*; D011446:Prospective Studies; D011758:Pyrroles / Q000008:administration & dosage* / Q000009:adverse effects; D012044:Regression Analysis; D016896:Treatment Outcome
D007211:Indoles; D011758:Pyrroles; D010894:Piroxicam; C464577:toceranib phosphate; D003520:Cyclophosphamide; D016190:Carboplatin