DOI: 10.1200/op-26-00226 ISSN: 2688-1527

Impact of Zinc Supplementation and Topical Clobetasol on the Prevention of Regorafenib-Induced Hand-Foot Skin Reaction: The ZINCLO-HAND Study

Orhun Akdogan, Enes Yesilbas, Mesut Yılmaz, Fatma Keskin Uzundere, Ahmet Oruc, Ender Eren Ozcelik, Gorkem Turhan, Mehmet Kayaalp, Ilknur Deliktas Onur, Haydar Temizyurek, Yasemin Evlendi, Okan Avcı, Mahmut Kara, Galip Can Uyar, Hasibe Bilge Gür, Ugur Coskun, Kadriye Baskurt, Fatma Cetin, Aytug Uner, Ramazan Cosar, Cengiz Karacin, Gungor Utkan, Atila Yıldırım, Ahmet Bilgehan Sahin, Ahmet Ozet, Mehmet Artac, Muhammed Ali Kaplan, Kadriye Bir Yucel, Nuriye Ozdemir, Omer Dizdar, Ozan Yazıcı, Osman Sutcuoglu
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Purpose

Regorafenib-induced hand-foot skin reaction (HFSR) is a common dose-limiting toxicity. We evaluated whether prophylaxis with oral zinc plus topical clobetasol is associated with lower clinically significant HFSR compared with either strategy alone.

Methods

ZINCLO-HAND was a prospective, multicenter, pragmatic, nonrandomized comparative study across 13 oncology centers in Türkiye. Adults initiating regorafenib were managed at physician discretion with oral zinc, topical clobetasol propionate 0.05%, or the combination for 8 weeks. The primary end point was grade ≥2 HFSR within the prophylaxis period. Secondary end points included grade 3 HFSR, treatment modification, relative dose intensity, and patient-reported outcomes.

Results

Of 179 enrolled patients, 156 were evaluable: zinc, n = 49; clobetasol, n = 52; combination, n = 55. Grade ≥2 HFSR occurred in 38.8%, 38.5%, and 16.4% of patients, respectively ( P = .016). In multivariable logistic regression adjusted for age, Eastern Cooperative Oncology Group performance status, tumor type, and initial regorafenib dose intensity, zinc monotherapy (adjusted odds ratio [OR], 3.37 [95% CI, 1.30 to 8.71]; P = .012) and clobetasol monotherapy (adjusted OR, 3.15 [95% CI, 1.26 to 7.88]; P = .014) were associated with higher odds of grade ≥2 HFSR versus combination prophylaxis. Median relative dose intensity was comparable across groups. HFSR-attributable treatment modification occurred in 30.6%, 28.8%, and 12.7% of patients, respectively.

Conclusion

In this nonrandomized prospective cohort, zinc plus topical clobetasol was associated with lower clinically significant regorafenib-induced HFSR and fewer HFSR-attributable treatment modifications. These findings support consideration of combination prophylaxis in routine practice and warrant randomized confirmation.

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