# Hand-foot syndrome and hand-foot skin reaction: prevention, skin care and dose changes

Source: https://onco.cc/protocols/hand-foot-syndrome-prevention-and-dose-modification/  
OnCo record `hand-foot-syndrome-prevention-and-dose-modification` (Protocol). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Capecitabine, liposomal doxorubicin and tablets such as sorafenib and regorafenib can make the palms and soles red, sore, peeling or blistered. From the start, avoid rubbing, heat and long soaks, wear well-fitting shoes and moisturise daily; with sorafenib, a 10 per cent urea cream from day one helps. If hands or feet become painful or limit what you do, stop capecitabine and call your team.

## Summary

Hand-foot syndrome (HFS) from capecitabine and pegylated liposomal doxorubicin, and hand-foot skin reaction (HFSR) from multikinase inhibitors, are managed by prevention, inspection at every cycle, and dose modification by CTCAE grade. Labels set the dose rules: capecitabine is withheld for grade 2 or worse until grade 0 to 1 and restarted at 100, 75 or 50 per cent of the current dose by occurrence (grade 2) or at 75 or 50 per cent (grade 3), and patients are told to stop the tablets themselves at grade 2; liposomal doxorubicin is delayed up to 2 weeks for grade 2 or worse and reduced by 25 per cent after grade 3; regorafenib is reduced to 120 mg at the first grade 2 HFSR and to 80 mg if it recurs, and interrupted for at least 7 days at grade 3.

For prevention, general measures (avoiding friction, heat and water exposure, fitted gloves and footwear, regular emollients) are universal advice without randomised proof. 10 per cent urea cream three times daily from day 1 of sorafenib lowered any-grade HFSR (56.0 against 73.6 per cent) and grade 2 or worse HFSR (20.7 against 29.2 per cent) in an open trial of 871 people; a blinded trial of 20 per cent urea was not significant on its primary measure. With capecitabine, oral celecoxib reduces grade 2 or worse HFS in network meta-analyses but carries cardiovascular and gastrointestinal risk; topical diclofenac gel reduced grade 2 to 3 HFS from 15.0 to 3.8 per cent in the D-TORCH trial and leads the 2026 network meta-analysis, but a 2026 real-world study found no benefit and a Japanese phase 3 trial is under way. Pyridoxine does not work. The ESMO 2021 guideline could not be read.

## Fields

- Kind: Protocol
- Last checked: 2026-11-11
- Also known as: hand-foot syndrome; HFS; palmar-plantar erythrodysesthesia; PPE; PPES; hand-foot skin reaction; HFSR; capecitabine hand-foot syndrome; urea cream for hand-foot; topical diclofenac for hand-foot syndrome
- Tags: protocol; hand-foot-syndrome; skin-toxicity; supportive-care

## Connected records

- drugs: [Cabozantinib](https://onco.cc/drugs/cabozantinib/), [Capecitabine](https://onco.cc/drugs/capecitabine/), [CAPOX (capecitabine, oxaliplatin)](https://onco.cc/drugs/capox/), [Celecoxib](https://onco.cc/drugs/celecoxib/), [Lenvatinib](https://onco.cc/drugs/lenvatinib/), [Pegylated liposomal doxorubicin](https://onco.cc/drugs/pegylated-liposomal-doxorubicin/), [Regorafenib](https://onco.cc/drugs/regorafenib/), [Sorafenib](https://onco.cc/drugs/sorafenib/), [Sunitinib](https://onco.cc/drugs/sunitinib/), [Tegafur, gimeracil and oteracil (S-1)](https://onco.cc/drugs/tegafur-gimeracil-oteracil/)
- fronts: [Supportive Care & Survivorship](https://onco.cc/fronts/supportive-care/)
- technologies: [Vitamin B6 (pyridoxine) for hand-foot syndrome and other uses](https://onco.cc/technologies/vitamin-b6-pyridoxine/)
- terms: [Hand-foot syndrome and hand-foot skin reaction](https://onco.cc/terms/hand-foot-syndrome/)
- ideas: [Anti-inflammatory gel on the palms and soles from the first day of capecitabine](https://onco.cc/ideas/idea-upgrade-topical-diclofenac-during-capecitabine/)

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