Summary: OncoLAR® is an agent that blocks the production of insulin-like growth factor (IGF-I), a hormone that is believed to enhance the survival of cancer cells. This study evaluated the effects of OncoLAR® in canine patients being treated with chemotherapy for osteosarcoma. A comparison was made in this group of study patients to osteosarcoma patients receiving chemotherapy but not OncoLAR®. Results showed significant suppression of IGF-I in patients treated with OncoLAR®, but there was no improvement in cancer cell destruction or patient survival time using this agent.

Publication: Khanna C , Prehn J, Yeung C, Caylor J, Bose S, Cassaday RJacob S, Helman L. Randomized trial of OncoLAR® (SMS-201 995pa LAR) and carboplatin versus carbplatin alone in dogs with naturally occurring osteogenic sarcoma. Clinical Cancer Res In Press, 7/1/02.

Background: Osteosarcoma is the most common primary tumor of bone. Several lines of evidence suggest the role of the insulin-like growth factor - growth hormone pathway in the biology of this cancer. Insulin like growth factor has been demonstrated to act as a survival signal for cancer cells, and as such has been hypothesized to be a mechanism of resistance against chemotherapy-induced death. OncoLAR® is a novel long acting analog of somatostatin that results in growth hormone blockade from the pituitary and therein suppression of serum insulin-like growth hormone release from the liver. The use of OncoLAR® pediatric osteosarcoma patients resulted in approximately fifty percent suppression in serum IGF-I levels with limited toxicity.

Methods: To determine if insulin-like growth factor suppression will decrease chemotherapy resistance by eliminating an important survival signal to osteosarcoma cells we conducted a randomized, blinded, placebo-controlled pre-clinical study in pet dogs with naturally occurring osteosarcoma. The trial compared primary tumor necrosis and apoptosis and survival of pet dogs receiving OncoLAR® and carboplatin chemotherapy compared to a placebo and carboplatin.

Results: demonstrated suppression of serum insulin-like growth factor levels by approximately 46% without toxicity in dogs receiving OncoLAR®. No differences in primary tumor necrosis, apoptosis, tumor insulin-like growth factor mRNA expression, or survival were seen between the two treatment groups.

Conclusions: Results suggest that suppression of insulin-like growth factor levels by the extent and/or duration achieved in the trial was not sufficient to improve chemotherapy related anti-tumor effects in pet dogs with osteosarcoma.