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The development of regorafenib as a treatment for patients with colorectal cancer progressed rapidly from phase I to approval. As a result of this rapid development timeline, many of the strategies for treatment with the multikinase inhibitor still need to be perfected, specifically in regard to side effect management, notes lead investigator Axel Grothey, MD.
In the pivotal phase III CORRECT study, 760 patients were randomized in a 2:1 ratio to regorafenib or placebo following progression on standard treatments. The trial found a significant median overall survival of 6.4 months compared with 5.0 months in patients who received placebo (HR = 0.77; P
= .0052). The results were the basis for the FDA approval in September 2012.
The most frequent regorafenib-related side effects include hand–foot skin reaction, fatigue, diarrhea, hypertension, and rash. For regorafenib, toxicity management is very important, since many of the critical side effects occur within the first 2 weeks of treatment, Grothey notes. To counter these early side effects, panelists administered regorafenib at a half dose of 80 mg rather than 160 mg, although this decision is not supported by clinical trial data. To help catch side effects early, Grothey suggests monitoring patients on a weekly basis during the first 2 cycles.
Several approaches could be utilized to obtain further data on the management of side effects with regorafenib, including registries and clinical trials, notes Charles D. Blanke, MD. At this point, the impact of dose reductions on efficacy remains unknown. As a result, some oncologists do not utilize the early dose reduction strategy, states Tanios S. Bekaii-Saab, MD.