Capecitabine-Induced Hand-Foot Syndrome

Definition and Clinical Characteristics

The European Society for Medical Oncology (ESMO) defines hand-foot syndrome as a cutaneous disorder characterized by erythema, edema, dysesthesia, and pain in the palms and soles, affecting up to 50-60% of patients on monotherapy and up to 73% in some studies 1, 2
The American College of Oncology recommends that patients with hand-foot syndrome may experience symptoms such as tingling, numbness, and paresthesias as initial symptoms, followed by progression to desquamation, blisters, ulcers, and bleeding in severe cases 2
The median time to onset is 79 days (range 11-360 days) after starting capecitabina, and lesions can extend to the dorsum of hands and feet or intertriginous areas 2

The incidence of hand-foot syndrome varies depending on the clinical context, with monotherapy rates ranging from 50-60% (grade 3-4 in 5-10%) and combination therapy rates up to 73.4% (grade 3 in 11.1%) 1, 2, 3
Risk factors include female sex, age ≥80 years, poor performance status, and pre-existing hyperkeratosis 1, 2, 5

The ESMO 2021 guidelines recommend preventive measures, including avoiding mechanical stress, chemical stress, and treating predisposing factors such as hyperkeratosis before starting therapy 1, 5
Topical preventive treatments include urea 10% cream three times a day, which has been shown to significantly reduce the incidence of hand-foot syndrome 1, 5
Pharmacological preventive treatments include celecoxib 200 mg twice a day, which has been shown to prevent hand-foot syndrome in patients with metastatic colorectal cancer 1, 4, 5

For grade 1 hand-foot syndrome, continue capecitabine at the current dose and monitor for changes in severity, and use high-potency topical corticosteroids (e.g., clobetasol propionate 0.05%) twice a day 1, 5
For grade 2 hand-foot syndrome, continue capecitabine at the current dose and monitor for changes in severity, and use high-potency topical corticosteroids twice a day 5
For grade ≥3 or intolerable grade 2 hand-foot syndrome, interrupt treatment until severity decreases to grade 0-1, and continue treatment of the cutaneous reaction with high-potency topical corticosteroids twice a day 5

For hyperkeratosis, use topical keratolytics (salicylic acid 5-10% or urea 10-40%) 5
For cutaneous inflammation, use high-potency topical corticosteroids 2
For erosions and ulcers, use antiseptic solutions (silver sulfadiazine 1%, polyhexanide 0.02-0.04%) 5
For pain, use lidocaine 5% cream or patches on painful areas of hands and feet to allow daily activities 1, 5