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Biodegradable Cisplatin Polymer in Limb-Sparing Surgery for Canine Osteosarcoma

From the Departments of Clinical Sciences (SJW, JML, RCS, WSD, VJJ) and Microbiology, Immunology, and Pathology (BEP), College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, Colorado; Comprehensive Cancer Center, Biostatistics and Computing (JLJ), Duke University Medical Center, Durham, North Carolina; Kensey Nash Corporation (JHB), Exton, Pennsylvania; and National Research Council (EBD), Washington, DC.

Correspondence: Address correspondence and reprint requests to: Stephen J. Withrow, DVM, Animal Cancer Center, Colorado State University Veterinary Teaching Hospital, 300 West Drake Road, Fort Collins, CO 80523; Fax: 970-297-1254; E-mail: swithrow{at}colostate.edu

Background: The rate of local recurrence of osteosarcoma after limb-sparing surgery in dogs and humans has been reported up to 28%. The primary purpose of this study was to determine whether a biodegradable cisplatin-containing implant (OPLA-Pt), inserted into the limb-sparing surgery site at the time of surgery, would decrease the rate of local recurrence. Secondary aims included evaluation of systemic toxicity associated with the release of cisplatin from the implant and identification of prognostic factors associated with limb-sparing surgery for osteosarcoma in dogs.

Methods: Eighty dogs with spontaneously occurring osteosarcoma were treated with limb-sparing surgery. They were randomized to receive the biodegradable implant either without cisplatin (control group) or with cisplatin (OPLA-Pt group) and were targeted to receive four doses of an adjuvant cisplatin chemotherapy protocol.

Results: Although this was not statistically significant (P = .071), dogs in the OPLA-Pt group were 53.5% less likely to develop local recurrence than dogs in the control group. There were no significant differences in systemic toxicity between treatment arms. Incomplete surgical resection, absence of infection, and fewer than four doses of adjuvant chemotherapy had a significant correlation with local recurrence and survival according to univariate analyses, although only incomplete surgical resection remained significant for local recurrence after multivariate analysis.

Conclusions: Local tumor recurrence may be decreased after limb-sparing surgery by use of biodegradable implants impregnated with chemotherapeutic agents.

Key Words: Osteosarcoma • Limb-sparing surgery • Local chemotherapy • Local tumor recurrence

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