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

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

Topical interventions for preventing hand-foot syndrome resulting from antineoplastic therapy: A scoping review

“…Other topical interventions were mapped, such as hydrocolloid dressing containing ceramide ( 3 . 45 ) ; topical neurotropin ( 14 ) ; bis-glyceryl ascorbate ( 27 ) ; topical heparin ( 32 . 50 ) ; 1% topical pyridoxine (vitamin B6) ( 11 ) ; hyaluronic acid ( 49 ) ; topical lanolin ( 49 ) ; isolated topical ( 49 , 57 ) uridine, or uridine associated with 10% thymine ( 49 ) ; hydrocolloid dressing ( 52 ) ; topical DMSO (dimethyl sulfoxide) ( 49 , 55 , 63 ) ; vaseline ( 56 ) ; topical eniluracil ( 57 ) ; as well as the use of UV A and B sunscreen (Blue Lizard ® ) ( 60 ) .…”

“…The publication period of the studies ranged from 2004 to 2023, being more concentrated in 2022 (n = 7) (12,(27)(28)(29)(30)(31)(32) . Ten studies were carried out in the United States of America (n = 10) (3,33,47,50,(58)(59)(60)(61)(62)(63) .…”

“…Ten studies were carried out in the United States of America (n = 10) (3,33,47,50,(58)(59)(60)(61)(62)(63) . Regarding the design, twenty studies were randomized clinical trials (RCT) (n = 20) (27,28,(31)(32)(33)(34)(35)(36)(37)(38)(42)(43)(44)46,48,(52)(53)(54)58) . The scales used by the RCT to classify HFS were the Common Terminology Criteria for Adverse Events (CTCAE) (n = 17) (3,12,13,15,27,(32)(33)(34)36,37,41,43,(52)(53)(54)58) ; World Health Organization Hand-Foot Syndrome Rating Scale (WHO HFS) (n = 6) (28,29,31,35,…”

“…Regarding the design, twenty studies were randomized clinical trials (RCT) (n = 20) (27,28,(31)(32)(33)(34)(35)(36)(37)(38)(42)(43)(44)46,48,(52)(53)(54)58) . The scales used by the RCT to classify HFS were the Common Terminology Criteria for Adverse Events (CTCAE) (n = 17) (3,12,13,15,27,(32)(33)(34)36,37,41,43,(52)(53)(54)58) ; World Health Organization Hand-Foot Syndrome Rating Scale (WHO HFS) (n = 6) (28,29,31,35,41,42) . A study (41) cited the Canadian National Cancer Institute Clinical Trials Group (CTG) scale, as well as the two previous scales (WHO HFS and CTCAE).…”

Intervenções tópicas para prevenção de síndrome mão-pé decorrente de terapia antineoplásica: revisão de escopo

“…O período de publicação dos estudos variou do ano de 2004 ao ano de 2023, concentrando-se no ano 2022 (n = 7) (12,(27)(28)(29)(30)(31)(32) . Dez estudos foram desenvolvidos nos Estados Unidos da América (n = 10) (3,33,47,50,(58)(59)(60)(61)(62)(63) .…”