Clinical management of regorafenib in the treatment of patients with advanced colorectal cancer

Abstract

Colorectal cancer is one of the most common tumors worldwide and at least 50 % of patients with this disease develop metastases. In this setting, additional treatment options are needed for patients presenting disease progression after exhausting all standard therapies. Regorafenib is an orally administered multikinase inhibitor which has been shown to provide survival benefits to patients with metastatic colorectal cancer (mCRC). Although most adverse events (AEs) associated with regorafenib may resolve within the first 8 weeks of treatment, some of them may require dose reduction or treatment interruption. Overall, while remaining aware of the safety profile of regorafenib and how to manage the most common toxicities related to its use, this drug should be considered a new standard of care for patients with pretreated mCRC. This review addresses practical aspects of its use, such as dosing, patient monitoring, and management of the most common regorafenib-related AEs.

Fig. 1

Dose modification/delay for toxicities related to regorafenib (except hand-foot skin reaction, hypertension and liver function test abnormalities). According to Common Terminology Criteria for Adverse Events (CTCAE) v 4.0. ^aExcludes alopecia, non-refractory nausea/vomiting, non-refractory hypersensitivity and asymptomatic laboratory abnormalities. ^bIf no recovery after a 4 week delay, treatment will be permanently discontinued

Fig. 2

Dose modification/delay of regorafenib in patients with hand-foot skin reaction. According to Common Terminology Criteria for Adverse Events (CTCAE) v 4.0. ^aIn case of grade 3 hand-foot skin reaction, a dose re-escalation is permitted only during first occurrence. ADL activities of daily living, HFSR hand-foot skin reaction

Fig. 3

Management of treatment-emergent hypertension in patients treated with regorafenib. According to Common Terminology Criteria for Adverse Events (CTCAE) v 4.0. DBP diastolic blood pressure, HBP high blood pressure, SBP systolic blood pressure, WNL within normal limits

Fig. 4

Dose modification/delay for ALT and/or AST and/or bilirubin increases related to regorafenib. According to Common Terminology Criteria for Adverse Events (CTCAE) v 4.0. ^aIf all values remain stable for two cycles, dose re-escalation may be considered at the discretion of the investigator. After re-escalation ALT, AST and bilirubin should be checked twice a week for 2 weeks, followed by weekly assessments for at least 4 weeks. ^bIn case of discontinuation ALT, AST and bilirubin should be checked twice a week for 2 weeks, followed by weekly assessments until recovery to baseline. General notes: patients requiring interruption for 4 weeks must stop treatment permanently. If more than 2 dose reductions are required, treatment will be discontinued. ALT alanine aminotransferase, AST aspartate aminotransferase, ULN upper limit of normal