INTRACAVITARY TREATMENT OF SOFT TISSUE SARCOMAS IN DOGS USING CISPLATIN IN A BIODEGRADABLE POLYMER

DERNELL WS, WITHROW SJ, STRAW RC, LAFFERTY MH. (Colorado State University, College of Veterinary Medicine and Biomedical Science, Fort Collins, CO 80523)

Soft tissue sarcomas (STS) in dogs have similar biologic behavior to the same disease in people with the exception of an overall lower metastatic rate. These tumors are characterized by a locally aggressive nature with a high rate of local tumor recurrence following incomplete resection. The purpose of this study was to evaluate the toxicity and efficacy for local tumor control of cisplatin released from a biodegradable polymer sponge (open cell polylactic acid or OPLA) as an adjunct to resection of STS in dogs.

A histologically incomplete (marginal) resection was performed in cases of histologically confirmed STS and OPLA containing cisplatin (OPLA-Pt) at 8% was implanted within the surgical site (intracavitary). A multifactorial analysis was performed using Cox proportional hazards model for the effect of tumor size, location, grade, previous treatment as well as intracavitary dose and dose based on body surface area (m²) on time to recurrence. Significance was set at p<=0.05.

Thirty dogs (32 tumors) were entered into the study, 12 following previous incomplete resection. Twenty-one of 32 tumors (66%) were on the distal extremities and 10 about the trunk or head. Median tumor diameter was 3 cm with a range of 1-15 cm. Median dose/m² was 34.5 mg with a range of 5.3-133.3 mg. Swelling, with or without drainage occurred in 19/32 implantation sites (60%). The OPLA-Pt was removed from 9/32 sites (28%). Partial wound dehiscence occurred in 6/32 tumors (19%). Median follow-up time was 335 days with a range of 113-1580 days. 11 dogs died, 5 with tumor disease; 3 with local recurrence, two with metastasis and one with local recurrence and metastasis. Nineteen dogs are alive without recurrent disease or metastasis. Local recurrence occurred in 10/32 (31%) of wounds implanted with OPLA-Pt. Median time to recurrence was greater than 640 days (range 30-640 days) and was not defined by life table analysis. Median time to metastasis was 978 days (range 100-978 days). Median Survival was 1021 days (range 44-1021 days). Of the factors analyzed, only tumor grade had an effect on local recurrence. Higher tumor grade had a significant (p=0.031) negative effect on local recurrence with a hazard ratio of 871.2 (95% confidence intervals of 1.854-409400) for grade III tumors compared to grade I.

Rate of recurrence appeared to be better using intracavitary cisplatin compared to previous reports of STS treated by marginal surgery alone, and comparable to marginal resection followed by external beam radiotherapy. A relatively high complication rate indicates the need for further evaluation of other delivery systems. This method of treatment of this spontaneous tumor disease in the dog may serve as a model for treatment of STS in people as well as for intracavitary chemotherapy in general.