Association of Hand-Foot Skin Reaction with Regorafenib Efficacy in the Treatment of Metastatic Colorectal Cancer

Abstract

Purpose: Hand-foot skin reaction (HFSR) can deteriorate quality of life in patients receiving regorafenib. Cutaneous toxicity is a main adverse effect of multikinase inhibitors and has also been associated with clinical outcome. This study assessed the association between the antitumor efficacy of regorafenib and HFSR in patients with metastatic colorectal cancer (mCRC). Methods: Patients who received regorafenib at 160 mg/day during the first 3 weeks of each 4-week cycle were divided into subgroups based on whether they developed HFSR between May 2013 and October 2015. Estimates of overall survival and progression-free survival were calculated using the Kaplan-Meier method. Results: Ninety-seven patients received at least one dose of regorafenib in this retrospective study. Of these patients, 81.4% (n = 79) experienced HFSR of any grade, and 34.0% (n = 33) had grade 3 HFSR. Among those patients with HFSR at any time during the study, 68.0% (n = 66) underwent the first HFSR event (any grade) during cycle 1. Both overall survival and progression-free survival were improved in patients who had HFSR grade ≥2 at any time compared with those who had HFSR grade ≤1. Multivariate logistic regression analysis revealed a history of HFSR grade ≥2 induced by capecitabine as a significant risk factor for severe HFSR (grade ≥2). Conclusions: Patients with mCRC treated using regorafenib who experienced severe HFSR showed better overall survival than patients without severe HFSR. Severe HFSR may offer an early surrogate marker for the efficacy of regorafenib in patients with mCRC.

<p>The Efficacy and Safety of Apatinib in Refractory/Relapse Advanced Pediatric Solid Tumor: A Retrospective Study</p>

“…The hand-foot syndrome was proposed to be a predictive biomarker for assessing the efficacy of anti-angiogenic drugs. 36,37 In our study, patients who had hand-foot syndrome had a median PFS of 8.0 (95% CI 1.7-14.3) months, compared to 3.0 (95% CI 1.6-4.4) months in those who did not, but the significant difference was not achieved (p=0.163).…”

Sorafenib-Regorafenib Sequential Therapy in Japanese Patients with Unresectable Hepatocellular Carcinoma—Relative Dose Intensity and Post-Regorafenib Therapies in Real World Practice

“…As favorable clinical factors associated with OS in regorafenib therapy, we revealed that 1M-RDI ≥ 50% (HR 0.16, 95% CI 0.05–0.50, p = 0.001) and HFSR during regorafenib therapy (HR 0.06, 95% CI 0.01–0.28, p = 0.0004) were independently associated with OS. Previous studies [23,24,25] reported that patients with metastatic colorectal cancer who were treated with regorafenib—and who experienced HFSR—showed better OS than patients without HFSR. The correlation of HRSR and survival has also been reported in the patients who enrolled the RESORCE trial [26].…”

Relationship between adverse events associated with lenvatinib treatment for thyroid cancer and patient prognosis

“…However, the prognosis of TKIs is favorable despite the appearance of AEs. In particular, the appearance of hand-foot syndrome (HFS) is reportedly correlated with prognosis for several TKIs (11)(12)(13). This retrospective study aimed to verify the AEs of lenvatinib in the real-world setting and clarify whether life-threatening AEs and HFS are markers of good prognosis as previously reported.…”

“…The frequency of HFS is high in Japan, as has been reported for several TKIs (13). Although the precise mechanisms by which multikinase inhibitors cause HFS remain unknown, the antiangiogenic activity of these drugs may inhibit vascular repair mechanisms in high-pressure areas, such as the palms and soles, which are repeatedly exposed to subclinical trauma (23).…”