Tolerability and efficacy of regorafenib in patients with unresectable metastatic colorectal cancer

BACKGROUND: Regorafenib is an orally administered multikinase inhibitor that was approved for the treatment of unresectable metastatic colorectal cancer in Japan last year, following an international phase 3 trial(CORRECT)that provided evidence of a survival benefit. However, some concerns remain about high odd ratios of specific adverse events. OBJECTIVES AND METHODS: We examined the clinical records of 16 patients(age: 57-78 years)treated with regorafenib for metastatic colorectal cancer that had progressed after all standard therapies were administered. Patients received either 160 mg(standard dose)or 80 mg(reduced at the physician's discretion)of regorafenib orally once a day, for the first 3 weeks of each 4-week cycle. Predefined dose reduction(by 40 mg, once)and dose interruption were permitted to manage treatment-related toxic effects. RESULTS: The median duration of treatment was 6.5 weeks(interquartile ratio[IQR]: 3.8-21.8). Dose modifications were required in 87.5% of patients, resulting in a relative dose intensity of 48.8%. Adverse events of grade 3 or higher related to regorafenib were hand-foot skin reactions(44%), fatigue(13%), thrombocytopenia(13%), anorexia(6%), and hypertension( 6%), in addition to severe drug-induced liver injury in 1 patient. Disease control was achieved in 75.0%(95% confidence interval[CI]: 50.0-93.8)of patients, although no patient had a partial response. Progression-free survival(PFS) and overall survival(OS)were 9.0 weeks(8.5-9.5 weeks)and 26.6 weeks(5.0-48.1 weeks), respectively. CONCLUSION: The efficacy of regorafenib was confirmed in late-stage cases that were refractory to standard chemotherapies. Most adverse events were manageable, although treatment was discontinued permanently in some cases because of hand-foot skin reactions, fatigue, and liver injury. The duration of treatment was short, but disease control, OS, and PFS were similar to those found in the CORRECT trial.