Because the two drugs work in very different ways and both have low toxicity profiles, the researchers predicted they would have additive or even synergistic effects when used in combination. Pre-clinical studies in mice showed that, indeed, the two together work better than either alone, Dr. Thompson says.
Sorafenib, a tyrosine kinase inhibitor approved for use in December 2005 under the trademark Nexavar, blocks enzymes in cancer cells that promote tumor growth and also blocks blood vessel growth in tumors, thereby depriving the tumor of nutrients and oxygen. Although sorafenib does not typically cause a large shrinkage of the tumor, it can prevent the tumor from growing further, and has been shown to delay the progression, or growth, of kidney cancer, Dr. Thompson said.
Recombinant IL-21 activates the immune system to kill cancer cells. Immune therapies have been shown to work in kidney cancer in the past, but those previously available were very toxic and poorly tolerated by most patients. Recombinant IL-21 is well tolerated by most patients, Dr. Thompson said. In our clinical trial of recombinant IL-21 by itself, we saw encouraging responses in patients with kidney cancer.
Therefore, treatment with sorafenib may make the cancer more susceptible to a killing response by an activated immune system, he says. We are looking forward to the Phase II portion of the study to better evaluate the overall safety profile and anti-tumor activity, Dr. Thompson said.
Preclinical characterization of OSI-906: A novel IGF-1R kinase inhibitor in clinical trials: Number C192
Preclinical studies suggest that a small molecule inhibitor of the insulin-like growth factor-1 receptor (IGF-1R) may be an effective anti
|Contact: Greg Lester|
American Association for Cancer Research