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

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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Journal
JCO Oncology Practice
Published
2026-11-04
DOI
https://doi.org/10.1200/op-26-00226
Primary Topic
Chemotherapy-related skin toxicity
Type
article
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article

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

Mehmet Kayaalp, Ahmet Bilgehan Şahin, Mesut Yılmaz, Nuriye Özdemir et al.
JCO Oncology Practice
Chemotherapy-related skin toxicity
article

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

Mehmet Kayaalp, Ahmet Bilgehan Şahin, Mesut Yılmaz, Nuriye Özdemir, Güngör Utkan, Kadriye Bır Yucel, Fatma Keskin Uzundere, Aytuğ Üner, Hasibe Bilge Gür, Orhun Akdoğan, Ahmet Özet, Ender Eren Özçelik, Osman Sütçüoğlu, Ozan Yazıcı, Mehmet Artaç, Ramazan Coşar, Ahmet Fatih Oruç, Atila Yıldırım, Yasemin EVLENDİ, Okan Avcı, Cengiz Karaçin, Kadriye Başkurt, Galip Can Uyar, İlknur Deliktaş Onur, Uğur Coşkun, Omer Dizdar, Mahmut Kara, Görkem Turhan, Enes Yeşilbaş, Haydar Temizyurek, Fatma ÇetiN, Muhammed Ali Kaplan
article en

Abstract

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.

JCO Oncology Practice
Sakarya University (TR), Van Yüzüncü Yıl Üniversitesi (TR), Dicle University (TR), Tekirdağ Namık Kemal University (TR), Bursa Uludağ Üni̇versi̇tesi̇ (TR), Ankara University (TR), Karadeniz Technical University (TR), Necmettin Erbakan University (TR), Afyonkarahisar Sağlık Bilimleri Üniversitesi (TR), Ankara Etlik City Hospital (TR), Ankara Dr. Abdurrahman Yurtaslan Oncology Training and Research Hospital (TR), Hacettepe University (TR), Gazi University (TR)
Openalex Percentile: Top 11%
Chemotherapy-related skin toxicity
DOISourceOpenAlex
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