BETHESDA, MD USA (UroToday.com) - In this session, Dr. Bjarnason reviewed institutional data regarding dose alterations as a result of toxicity in mRCC patients. Interestingly, Sunnybrook data seems to suggest that toxicity can be used to predict response to therapy. Based on this observation, a retrospective study was undertaken which showed that when dosing was changed due to side effects -- using one of two reduced dosing schedules -- that maximized time of treatment and overall survival were longer when the duration of drug-free time was shorter. Although this might seem counterintuitive, he was able to show that the groups were evenly matched in terms of Heng risk stratification and a variety of other clinico-pathologic factors.
Based on this retrospective observation, Dr Bjarnason hypothesizes that reduced dose, but with reduced drug-free interval, would both reduce toxicity and increase efficacy. This hypothesis is now being tested in a prospective trial. He also showed that serum AUC levels actually decrease in patients on long-term sunitinib, and showed data suggesting that RCC cells are able to sequester the drug into acidic lysosomes after long-term treatment as a means of therapy resistance. Increasing exposure of cells to drug might increase drug efficacy by reducing induced resistance.
Presented by:
Georg Bjarnason, MD, FRCPS(C)
Sunnybrook Health Sciences Centre
Reported by:
Reza Mehrazin, MD from the 14th Annual Meeting of the Society of Urologic Oncology (SUO) "Extraordinary Opportunities for Discovery" - December 4 - 6, 2013 - Bethesda, MD USA
Fox Chase Cancer Center, 333 Cottman Avenue, Philadelphia, PA USA
