EFFECT OF ZOLEDRONIC ACID ON CHONDROSARCOMA: IN VITRO AND IN VIVO STUDY USING A RAT MODEL

Abstract

Purpose of the study: Wide en bloc surgical resection is the treatment of choice for cure of chondrosarcoma. Despite local control of this primary bone tumor in 60–80% of patients, mortality remains high. Recent studies suggest that biphosphonates can provide promising perspectives for the treatment of malignant bone tumors, even for primary tumors such as osteosarcoma. We report here the results obtained when using zoledronate for Swarm chondrosarcoma in an in vivo rat model and the effect of this compound on tumor cells in vitro.

Material and methods: Swarm chondrosarcoma was implanted in three series of 12 male Sprague Dawley rats. In series A, the animals were treated after implantation to death or sacrifice. In series B and C, the animals were treated a few days before curettage-resection then to death or sacrifice. Tumor growth was assessed by tumor size, presence of metastasis and death. Control series with PBS injections were also studied.

Results: Treatment with zoledronate inhibited tumor growth in all series. In series A, tumor size was significantly smaller in the treated animals (p=0.046). Tumor progression from day 19 to day 32 was significantly less for treated animals (p=0.046). Chance of survival was 0.667 for treated animals versus 0.3 for the controls. For series B and C, recurrence developed later in animals given zoledronate. Tumor size was greater in control animals compared with treated animals (p=0.043). Tumor progression from day 39 to day 49 was significantly greater in the control group (p=0.025). Cultures of cells extracted from the Swarm chondrosarcoma tumor also showed significantly inhibited growth in vitro for concentrations of zoledronic acid from 10 to 100 ml/l.

Discussion and conclusion: Zoledronic acid appears to inhibit growth of Swarm chondrosarcoma in all in vivo therapeutic schemas studied, confirming in vitro data. A more precise animal model better fitting clinical situations should provide more detailed information for use of this treatment after recurrence or in the event of intralesional surgery.