Osteosarcoma accounts for 5% of cancer related deaths in 12-17 year old humans. Limb sparing surgery is being performed on a limited but increasing basis. Local recurrence rates in humans range from 5 to 20%, often in spite of extensive preoperative local therapy. The biologic behavior of canine osteosarcoma is very similar to that in humans. Most canine osteosarcomas have more advanced local bony and soft tissue disease (Stage IIB) than is seen in humans, making it a challenging system for local control with limb sparing.
The aim of this project is to improve local control of osteosarcoma in dogs after limb sparing surgery with the use of a local release of cisplatin from a biogradable open cell meshwork matrix of polyactic acid (OPLA-Pt). The hypothesis is that dogs receiving local cisplatin (similar to intracavitary treatment) will have improved local control of tumor without an increase in local or systemic toxicity when compared to dogs not receiving local cisplatin. Should this hypothesis be correct, many more human patients would be eligible for limb sparing and the principles applied to osteosarcoma could be expanded to a wide variety to solid tumors. In years 10 through 13, two treatment groups will be evaluated. All dogs will undergo a marginal resection of local tumor, allograft replacement of resected bone, and four postoperative intravenous doses of cisplatin. Dogs will be randomized to receive local cisplatin or no local cisplatin and be evaluated for evidence of local recurrence. Pharmacokinetics of cisplatin release will be evaluated in serum and drain fluid by atomic absorption spectrometry. Healing of soft tissues and the bone allograft will be evaluated for differences between groups. Tumor kinetic parameters including potential doubling time and growth fraction will be determined using flow cytometry. This information will be correlated with the local tumor control and with metastatic disease to determine any predictive value. The last year of this proposal (year 14) will combine local cisplatin, hyperthermia and/or radiation to take advantage of the thermal and radiation sensitizing properties of cisplatin.
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