Prevention and management of adverse events related to regorafenib

Abstract

Regorafenib is an oral multikinase inhibitor that has shown antitumor activity in a range of solid tumors. Based on data from phase III clinical trials, regorafenib is indicated for the treatment of adult patients with metastatic colorectal cancer who have previously been treated with, or are not considered candidates for, other available therapies, and in patients with advanced gastrointestinal stromal tumors that cannot be surgically removed and no longer respond to other appropriate treatments. A panel of oncology nurses, research coordinators, and other medical oncology experts, experienced in the care of patients treated with regorafenib, met to discuss the best practice for the management of regorafenib-associated adverse events (AEs). The panel agreed that, in clinical trials and daily practice with regorafenib, AEs are common but mostly manageable. The most common and/or important AEs associated with regorafenib were considered to be hand–foot skin reaction, rash or desquamation, stomatitis, diarrhea, hypertension, liver abnormalities, and fatigue. This manuscript describes the experience and recommendations of the panel for managing these AEs in everyday clinical practice. Appropriate education, monitoring, and management are considered essential for reducing the incidence, duration, and severity of regorafenib-associated AEs.

Multikinase Inhibitor-Induced Hand–Foot Skin Reaction: A Review of Clinical Presentation, Pathogenesis, and Management

“…Appropriate preventive measures can decrease the [79]. Despite the relatively high incidence of MKI-induced HFSR, evidence to support most preventive measures is very limited.…”

Improving Patient Outcomes with Regorafenib for Metastatic Colorectal Cancer - Patient Selection, Dosing, Patient Education, Prophylaxis, and Management of Adverse Events

“…Fatigue can be highly distressing to patients due to its substantial impact on quality of life, with grade 2 fatigue affecting instrumental activities of daily living such as telephoning people or doing the housework, and grade 3 fatigue limiting self-care. Furthermore, rest typically does not relieve fatigue symptoms [16,17]. In CORRECT, 9% of patients experienced grade 3 or higher fatigue which is similar to the grade 3 or higher fatigue rates observed in CONCUR as well as GRID, another pivotal trial of regorafenib in patients with gastrointestinal stromal tumors (3 and 2% of patients, respectively) [7,9,18].…”

“…Diarrhea is common during regorafenib treatment but generally tends to be of an NCI CTCAE v3.0 grade 1 or 2 intensity [10,15]. Diarrhea should be rapidly treated, as dehydration due to loss of electrolytes and fluid in patients with persistent or severe diarrhea can be life-threatening [16]. If the diarrhea does not resolve within 24 h or concurrent fever also occurs, patients should immediately consult a doctor or contact a hospital.…”

“…However, 1 case of fatal liver dysfunction possibly associated with regorafenib was reported in CORRECT (0.2% of regorafenib recipients) as well as in GRID (0.8% of regorafenib recipients) [7,18]. Therefore, ALT, AST, and bilirubin should be assessed every 2 weeks for the first 2 cycles of treatment [10,16]. In the case of increasing transaminases and bilirubin levels, dose modifications or treatment discontinuation is mandatory depending on severity and persistence.…”

“…Recent data have suggested that nightly dosing of regorafenib might relieve fatigue symptoms [20]. Additionally, close contact with the healthcare team can be helpful for early diagnosis of developing or worsening fatigue [16]. …”