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. KleinDavid M. Ruslander, Doug H. Thamm, Brenda Phillips, Gerald Post

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34 Scopus citations

Abstract

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. Methods and Findings: 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.

Original languageEnglish (US)
Article numbere0124889
JournalPloS one
Volume10
Issue number4
DOIs
StatePublished - Apr 29 2015

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    London, C. A., Gardner, H. L., Mathie, T., Stingle, N., Portela, R., Pennell, M. L., Clifford, C. A., Rosenberg, M. P., Vail, D. M., Williams, L. E., Cronin, K. L., Wilson-Robles, H., Borgatti, A., Henry, C. J., Bailey, D. B., Locke, J., Northrup, N. C., Crawford-Jakubiak, M., Gill, V. L., ... Post, G. (2015). Impact of toceranib/piroxicam/cyclophosphamide maintenance therapy on outcome of dogs with appendicular osteosarcoma following amputation and carboplatin chemotherapy: A multi-institutional study. PloS one, 10(4), [e0124889]. https://doi.org/10.1371/journal.pone.0124889