Topical heparin as an effective and safe treatment for patients with capecitabine-induced hand-foot syndrome: results of a phase IIA trial supported by proteomic profiling of skin biopsies

Analia Rodríguez-Garzotto; Lara Iglesias-Docampo; C Vanesa Díaz-García; Isabel Ruppen; Pilar Ximénez-Embún; Carlos Gómez; J Luis Rodríguez-Peralto; Javier Ortiz de Frutos; Jose A Lopez-Martin; Cristina Grávalos; Hernán Cortés-Funes; M Teresa Agulló-Ortuño

doi:10.1177/17588359221086911

Topical heparin as an effective and safe treatment for patients with capecitabine-induced hand-foot syndrome: results of a phase IIA trial supported by proteomic profiling of skin biopsies

Ther Adv Med Oncol. 2022 Mar 26:14:17588359221086911. doi: 10.1177/17588359221086911. eCollection 2022.

Affiliations

¹ Medical Oncology Department, Hospital Universitario 12 de Octubre, Madrid, Spain.
² Laboratory of Thoracic and Clinical-Translational Oncology, Instituto de Investigación Sanitaria Hospital 12 de Octubre (i + 12), Madrid, Spain.
³ Proteomics Unit, Spanish National Cancer Research Centre (CNIO), Madrid, Spain.
⁴ Pathology Department, Hospital Universitario 12 de Octubre, Madrid, Spain.
⁵ Dermatology Department, Hospital Universitario 12 de Octubre, Madrid, Spain.
⁶ Laboratory of Thoracic and Clinical-Translational Oncology, Instituto de Investigación Sanitaria Hospital 12 de Octubre (i + 12), Avda de Córdoba, s/n, 28041 Madrid, Spain.

Abstract

Background: Hand-foot syndrome (HFS) is a common adverse reaction associated with capecitabine chemotherapy that significantly affects the quality of life of patients. This study evaluates the safety and effectiveness of a topical heparin (TH) treatment on the clinical manifestations and anatomopathological alterations of capecitabine-induced HFS. In addition, we performed proteome profiling of skin biopsies obtained from patients with HFS at baseline and after heparin treatment.

Methods: Patients with grade ⩽ 2 HFS associated with capecitabine were included in this study. The primary end point was the effectiveness of TH in reducing HFS of any grade. Clinical improvement was evaluated by clinicians, and an improvement was perceived by patients who performed a weekly visual analog scale questionnaire. Secondary end points included a comparative histological analysis and protein expression in skin biopsies at baseline and after 3 weeks of HT treatment. Proteomic profiling was carried out using quantitative isobaric labelling and subsequently validated by a T-array.

Results: Twenty-one patients were included in the study. The median TH treatment time was 7.6 weeks (range = 3.6-41.6 weeks), and the median response time was 3.01 weeks (95% CI = 2.15-3.97). At the end of treatment, 19 of 21 patients (90.48%) responded to treatment with a decrease in one or more grades of HFS. None of the patients experienced adverse effects related to TH usage, nor did they suspend chemotherapy treatment. The main findings observed in skin biopsies after treatment were a decrease in hyperkeratosis and lymphocytic infiltrates. The proteomic analysis showed altered expression of 34 proteins that were mainly related to wound healing, cell growth, and the immune response.

Conclusion: Based on our results, topical heparin is an effective and safe treatment for clinical manifestations of HFS, probably due to the restauration of skin homeostasis after heparin treatment, as supported by our proteomics-derived data.

Trial registration: EudraCT 2009-018171-13.

Keywords: capecitabine; hand-foot syndrome; heparin; palmar-plantar erythrodysesthesia.