Osteosarcoma is characterized by a high rate of distant relapse following surgical resection of the primary tumor. Data from recent trials showed a 47% rate of distant spread compared to 6% local recurrence (Whelan et al. 2012). There is evidence, (pre-clinical and retrospective), in other cancers that peri-operative interventions may reduce the rate of distance recurrence. Ketorolac, commonly used for post-operative analgesia, is one such intervention. Retrospective data in breast cancer shows a reduced rate of distant relapse when used pre-operatively – prospective trials in breast cancer are on-going. Mechanistic data shows that ketorolac acts on the COX2/PGE2 pathway associated with the wound healing response and known to be over-expressed in osteosarcoma. Additional targets include Cdc42 and Rac1, which are active in the metastatic cascade in murine osteosarcoma models. Data from osteosarcoma patients shows that Rac1 overexpression is associated with an increased risk of metastasis.
Canine osteosarcoma is the ideal model of the disease. It is proposed that a single IV injection is administered prior to resection of the primary in dogs with spontaneous osteosarcoma. Outcomes include comparison of pre- and post-operative biomarkers and a reduction in PFS and OS in treated animals compared to a no-ketorolac group.