Management of Chemotherapy-Induced Hand-Foot Syndrome

Chemotherapy-induced hand-foot syndrome (HFS) is a dose-limiting dermatological toxicity characterised by erythema, swelling, dysaesthesia and pain of the palms and soles. It arises most commonly with agents such as capecitabine, 5-fluorouracil and taxanes and may necessitate dose reductions or treatment delays, adversely affecting tumour control. Management strategies combine preventive measures—including patient education, cooling techniques and moisturising emollients—with pharmacological interventions aimed at attenuating inflammation and keratinocyte damage. Topical therapies (emollients, keratolytics, non-steroidal anti-inflammatory gels) and systemic agents (corticosteroids, vitamin derivatives, proton pump inhibitors) have been evaluated in randomised and observational studies. Emerging approaches leverage mechanistic insights into inflammatory circuits and vascular–epidermal cross-talk to develop targeted prophylactic and therapeutic regimens. Multidisciplinary care, supportive skin care regimens and protocolised dose modifications remain central to optimising both quality of life and oncological outcomes in affected patients.

Research from Nature Portfolio

Recent clinical data demonstrate that systemic dexamethasone, administered in a higher daily dose, significantly reduces the incidence and severity of docetaxel-induced HFS in breast cancer patients. A retrospective analysis comparing 8 mg/day versus 4 mg/day regimens showed a marked decrease in all-grade HFS occurrence across treatment cycles, confirming dose-dependent anti-inflammatory protection without compromising oncological efficacy. In parallel, preclinical and pharmacovigilance studies have identified omeprazole, a proton pump inhibitor, as a potential prophylactic agent against capecitabine-induced HFS. In a mouse model, co-administration of omeprazole attenuated paw erythema, oedema and pro-inflammatory cytokine release. Analysis of a large adverse-event reporting database further indicated a lower reporting rate of palmar-plantar erythrodysesthesia among patients receiving proton pump inhibitors alongside capecitabine, suggesting real-world benefit of this repurposed therapy.

Management of Chemotherapy-Induced Hand-Foot Syndrome publication trend

The graph below shows the total number of articles in management of chemotherapy-induced hand-foot syndrome across all publications each year (not limited to Nature Index journals).

Technical terms

Hand-Foot Syndrome (HFS): A chemotherapy-related cutaneous toxicity characterised by redness, swelling and pain on the palms and soles.

Palmar-plantar erythrodysesthesia (PPE): Alternative term for HFS, denoting redness and dysaesthesia of palmar and plantar skin.

Hand–Foot Skin Reaction (HFSR): A variant of HFS associated with targeted agents, marked by hyperkeratosis and callus formation.

Capecitabine: An oral prodrug of 5-fluorouracil commonly used in colorectal and breast cancer regimens.

Docetaxel: A taxane chemotherapeutic agent frequently implicated in HFS through inflammatory pathways.

Dexamethasone: A systemic corticosteroid used to mitigate inflammatory chemotherapy side effects.

Omeprazole: A proton pump inhibitor with anti-inflammatory properties repurposed to prevent HFS.

Diclofenac: A topical non-steroidal anti-inflammatory drug evaluated for HFS prophylaxis.

Sirtuin 1 (SIRT1): A deacetylase implicated in keratinocyte hyperkeratosis and targetable by nicotinamide.

References

1. Evaluation of the impact of systemic dexamethasone dosage on docetaxel-induced hand-foot syndrome in patients with breast cancer. Scientific Reports (2024).
2. Use of omeprazole, the proton pump inhibitor, as a potential therapy for the capecitabine-induced hand-foot syndrome. Scientific Reports (2021).
3. Randomized double-blind, placebo-controlled study of topical diclofenac in the prevention of hand-foot syndrome in patients receiving capecitabine (the D-TORCH study). Trials (2022).
4. s-HBEGF/SIRT1 circuit-dictated crosstalk between vascular endothelial cells and keratinocytes mediates sorafenib-induced hand–foot skin reaction that can be reversed by nicotinamide. Cell Research (2020).
5. Pyridoxine for Prevention of Hand-Foot Syndrome Caused by Chemotherapy: A Systematic Review. PLOS ONE (2013).