PLoS ONE (Jan 2015)

Impact of Toceranib/Piroxicam/Cyclophosphamide Maintenance Therapy on Outcome of Dogs with Appendicular Osteosarcoma following Amputation and Carboplatin Chemotherapy: A Multi-Institutional Study.

  • Cheryl A London,
  • Heather L Gardner,
  • Tamra Mathie,
  • Nicole Stingle,
  • Roberta Portela,
  • Michael L Pennell,
  • Craig A Clifford,
  • Mona P Rosenberg,
  • David M Vail,
  • Laurel E Williams,
  • Kim L Cronin,
  • Heather Wilson-Robles,
  • Antonella Borgatti,
  • Carolyn J Henry,
  • Dennis B Bailey,
  • Jennifer Locke,
  • Nicole C Northrup,
  • Martin Crawford-Jakubiak,
  • Virginia L Gill,
  • Mary K Klein,
  • David M Ruslander,
  • Doug H Thamm,
  • Brenda Phillips,
  • Gerald Post

DOI
https://doi.org/10.1371/journal.pone.0124889
Journal volume & issue
Vol. 10, no. 4
p. e0124889

Abstract

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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.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.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.