115 Background: Regorafenib is an effective oral multikinase inhibitor approved for treatment-refractory metastatic colorectal cancer (mCRC). However, one of its most frequent and dose-limiting toxicities is hand–foot skin reaction (HFSR), with grade ≥2 events occurring in 35–40% of patients. Despite its clinical relevance, no standard prophylactic approach has been universally recommended in current guidelines. Phase II studies suggest that oral zinc supplementation and topical high-potency corticosteroids may reduce the severity of HFSR by preserving skin integrity and reducing inflammation. Yet, no comparative prospective study has evaluated their combined or separate prophylactic efficacy in this setting. Methods: The ZINCLO-HAND study (ClinicalTrials.gov ID: NCT06856590) is a multicenter, prospective, non-randomized trial conducted across 12 oncology centers in Türkiye. Patients with mCRC initiating regorafenib and having an ECOG performance status of 0–2 were enrolled. Based on physician preference, participants were assigned to one of three prophylaxis arms: (1) oral zinc tablets (50 mg/day), (2) topical clobetasol propionate 0.05% cream twice daily, or (3) combination of both. Prophylaxis was initiated concurrently with regorafenib and continued for 8 weeks. The primary endpoint was the incidence of grade ≥2 HFSR (CTCAE v5.0). Secondary endpoints included quality of life (FACT-G), HFSR symptom burden (HFS-14), fatigue, and emotional well-being scores. EORTC QLQ-C30 and FACT-Anxiety questionnaires were administered at baseline and at week 8 to evaluate quality of life and anxiety changes during regorafenib treatment across prophylactic groups. Results: Among 104 mCRC patients (median age: 66 range, 23–80; 56% male), prophylactic allocation was as follows: zinc-only (n=29), clobetasol-only (n=35), and combination (n=40). Overall, 28 patients (26.9%) developed grade ≥2 HFSR. The incidence was 38.5% in the zinc group, 34.3% in the clobetasol group, and significantly lower in the combination group at 12.5% (p=0.031). Compared to zinc monotherapy, combination prophylaxis reduced the risk of HFSR with an odds ratio of 0.27 (95% CI: 0.09–0.88). Grade 3 HFSR occurred in 3 patients in the zinc group, 2 in the clobetasol group, and 1 in the combination group. Conclusions: Combination prophylaxis with oral zinc and topical clobetasol significantly reduced the incidence of regorafenib-induced HFSR in patients with metastatic colorectal cancer. This strategy offers a promising, accessible, and low-cost intervention to improve treatment adherence and patient comfort during regorafenib therapy. Clinical trial information: NCT06856590 .
SÜTCÜOĞLU et al. (Sat,) studied this question.