Phase II trial of topical heparin as treatment for patients (pts) with hand-foot syndrome (HFS) induced by capecitabine (CAP).

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e19671 Background: Molecular physiopathology of HFS induced by CAP is unclear. Interruption or dose reduction of CAP is the only effective strategy. Aims: to evaluate efficacy and safety of a topical heparin Menaven gel® and to analyse expression levels of four biomarkers. Methods: This is a Simon 2-stage phase 2 trial: if >3 responses were achieved in the first 12 pts, the study proceeded to its second stage. Key entry criteria: Age >18 years, diagnosis of cancer in treatment with CAP, as single-agent or in combination, and presence of HFS grade (G) 1 or 2 (NCI-CTCAE version 3.0). Topical heparin was administered in palms and soles four times/day for three weeks (w). No other concurrent treatment for HFS was allowed. Physical examination and Visual Analogic Pain Scale (VAS) were assessed at baseline, and weekly. Changes were photographically documented by investigator. Skin biopsies of palms and blood samples were obtained at baseline and after 3w. Expression of thymidine phosphorylase (TP), dihydropyrimidine-dehydrogenase (DPD), Fibroblast Growth Factor (FGF) and Keratinocyte Growth Factor (KGFR) were analyzed by immunohistochemistry (IHC) and immunoperoxydase revelation in skin. TP and DPD mRNA expression was determined by quantitative real-time PCR in blood samples. Results: Between Oct/2010 and Jan/2011, 21 pts were included. So far, 16 pts are evaluable: 6 males, median age 61 y. Breast cancer (n=8), colorectal cancer (n=5) and others (n=3). Baseline HFS was G1 18% and G2 82%. CAP was administered as single-agent (n=4) and combination (n=12). Improvement of HFS was observed in 68% and 75% pts in w3 and 6, respectively. Median VAS decreased from 5,6 at baseline to 1,1 in w3, p<0,001. No changes were observed in the skin biopsies. However, high expression of TP was found in conjunction of decreased DPD in blood samples in 12pts with clear response. Definitive results from 21 subjects will be presented at the meeting. Conclusions: Our preliminary results suggest that topical heparin may be effective to relief CAP-induced HFS. A study evaluating topic heparin as a preventive therapy of HFS is planned.