LOS ANGELESA new oral kinase inhibitor that targets the transforming growth factor-beta (TGF-b) receptor reduced radiation-induced lung injury in a preclinical model, Mitchell S. Anscher, MD, reported at the plenary session of this year's ASTRO meeting (abstract 5).
TGF-b has multiple activities that may promote the development of lung injury after radiation therapy, and these activities are initiated by binding of the molecule to its receptors, said Dr. Anscher, a radiation oncologist at Virginia Commonwealth University.
Animal study of SM16
The study tested the effectiveness of SM16, a novel oral kinase inhibitor that interferes with the binding of TGF-b to its type 1 receptor. The agent is under development by Biogen Idec. The researchers divided 112 Sprague-Dawley rats into 8 groups of 14 rats each:
• Three groups did not receive any radiation; according to group, these rats were fed control chow, chow with low-dose SM16, or chow with high-dose SM16 for their lifespan.
• Five groups received a single fraction of 28 Gy to the right hemithorax; according to group, these rats were fed control chow; chow with low-dose or high-dose SM16 for their lifespan; or chow with low-dose or high-dose SM16 for 3 weeks, with a return to control chow thereafter. The drug-containing chow was started 7 days before radiation.
Body weight over time, a measure of drug toxicity, was similar across groups, with the exception of a lower weight in irradiated rats fed control chow, Dr. Anscher said.
Breathing frequency, a measure of impaired lung function, was significantly lower, by about 15%, between weeks 10 and 22 after radiation in the irradiated rats fed high-dose SM16 than in their irradiated counterparts fed control chow; short-term feeding with the high dose was associated with a smaller, nonsignificant reduction.