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With the use of multikinase inhibitors (MKIs) having emerged in recent years, skin toxicities such as hand-foot skin reaction (HFSR) are primary side effects, and they lack effective prediction methods. Here, we updated a previous systematic review by establishing a meta-analysis of the risk of developing HFSR among patients receiving MKIs and antivascular endothelial growth factor antibody. Publications from PubMed and abstracts presented at the American Society of Clinical Oncology Annual Meeting up to February 5, 2015, were searched to identify relevant studies, and a total of 236 patients with metastatic tumours in nine trials were included for analysis. In the meta-analysis, the pooled incidence rates of all-grade and high-grade HFSR among patients who received the combination therapy were 56.9% [95% confidence interval (CI), 45%-71.1%] and 14.3% (95% CI, 9%-24.2%), respectively, with significant differences observed with MKI monotherapy (P < .05). Further subgroup analysis demonstrated that increasing the dosages of bevacizumab (77.8% vs 51.1%, P = .04) and MKIs (64.3% vs 52.6%, P = .02) significantly increased HFSR incidence. Moreover, combination with chemotherapy exerted a minimal effect on HFSR risk (61% vs 55.3%, P = .5). This updated review and meta-analysis confirm the increased risk of HFSR incidence due to the use of MKIs and antivascular endothelial growth factor antibody. Thus, using these therapies requires safety standards., (© 2018 The Authors. Clinical and Experimental Pharmacology and Physiology Published by John Wiley & Sons Australia, Ltd.)

Regorafenib is a multikinase inhibitor for the treatment of metastatic colorectal cancer. Regorafenib-induced hand-foot skin reaction (HFSR) is a common side effect during treatment. The reported frequency of HFSR was 80% (grade 3: 28%) in the Japanese subpopulation in the CORRECT trial; however, more detailed data regarding HFSR in terms of onset and sites of susceptibility are unclear. Additionally, the risk factors for regorafenib-induced severe HFSR are unknown. The aim of this study was to compare HFSR between the hands and feet and identify preexisting risk factors for severe HFSR in Japanese patients receiving regorafenib. We retrospectively examined the onset and severity of HFSR on the hands and feet of patients with metastatic colorectal cancer treated with regorafenib from May 2013 to October 2015 in the Cancer Institute Hospital of the Japanese Foundation for Cancer Research. In addition, we examined the possible association between preexisting clinical factors and severe HFSR. Our results showed that no significant difference in the incidence of HFSR of any grade was observed between the hands (71%) and feet (74%) (p=0.63). The incidence of grade 3 HFSR was more frequent on the feet (33%) than on the hands (8%) (p<0.01). The onset of grade 3 HFSR was earlier on the feet than on the hands (p<0.001). No preexisting risk factor was identified. Our findings indicate that severe HFSR was more prevalent on the feet than on the hands, suggesting the need for appropriate screening for early detection and treatment of regorafenib-induced HSFR. [ABSTRACT FROM AUTHOR]