Regorafenib is a tyrosine kinase inhibitor indicated for the treatment of patients with metastatic colorectal cancer (mCRC) who have been previously treated with fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy, an anti-vascular endothelial growth factor receptor (VEGF) therapy, and, if KRAS wild-type positive, an anti-epidermal growth factor receptor (EGFR) therapy. The recommended dose is 160 mg orally once daily for the first 21 days of each 28-day cycle.1

Although effective at this dose for mCRC, a pivotal trial comparing regorafenib with placebo showed that at 160 mg daily, regorafenib caused asthenia/fatigue in 64% of patients, hand–foot skin reactions in 45% of patients, hypertension in 30% of patients, and rash in 26% of patients treated with the drug.2

Lower doses of regorafenib are also acceptable in patients who develop toxicities at the 160 mg dose. Reducing the dose of regorafenib to 120 mg is recommended for the first occurrence of grade 2 hand–foot skin reactions of any duration, after recovery of any grade 3 or 4 adverse reaction, and for grade 3 AST/ALT elevation as long as potential benefit outweighs the risk of hepatotoxicity.

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The dose can be further reduced to 80 mg after re-occurrence of grade 2 hand–foot skin reactions at the 120 mg dose and after recovery of grade 3 or 4 adverse reactions except hepatotoxicity at the 120 mg dose.1

“The problem with regorafenib is the lack of standardization of the starting dose among United States practices,” Tanios Bekaii-Saab, MD, FACP, section chief of gastrointestinal oncology at The Ohio State University, James Cancer Hospital and Solove Research Institute in Columbus, OH, said in an interview with Cancer Therapy Advisor. “Less than 50% of the [medical oncologists] in the country use the FDA-approved dose. The majority use a non-standardized dose schema.”