Table 1.

Management approaches for hand–foot skin reaction (HFSR) associated with licensed kinase inhibitors

Reference	Kinase inhibitor	Intervention	Outcome
Clinical studies
[40]	Sorafenib	10% urea-based cream three times daily + best supportive care (n = 439) or best supportive care alone excluding all creams (n = 432), starting on day 1 of sorafenib treatment, for up to 12 weeks	Compared with best supportive care alone, addition of urea-based cream resulted in: Significantly lower incidence of any-grade HFSR (P < 0.001) and grade ≥2 HFSR (P = 0.004) at week 12 Significantly longer median time to first occurrence of HFSR (P < 0.001) Improved patient quality of life
[41]	Sorafenib	Hydrocolloid dressing containing ceramide (group A, n = 17) versus 10% urea cream (group B, n = 16) for grade 1 HFSR on the soles of the feet	HFSR worsened to grade 2 or 3 in 29% of patients in group A and 69% of patients in group B (P = 0.03) Median time to grade 2 or 3 HFSR was significantly longer in group A than in group B (P = 0.03)
[42]	Sunitinib, sorafenib, or axitinib	Topical heparin-containing ointment, shock absorbers, and skin moisturizers (n = 26)	HFSR grade 1 resolved completely in 8/12 patients HFSR grade 2 symptoms reduced in 10/12 patients HFSR grade 3 downgraded to grade 2 in 2/2 patients Four patients required dose reductions; no patients had treatment interruption
[43]	Sorafenib	Vitamin E 300 mg/day (n = 10)	Marked effect after 10–12 days of initiation No need for sorafenib dose modification
[44]	Sorafenib or gefitinib	Taohongsiwu (traditional Chinese medicine; n = 60) versus oral vitamin B6 (n = 32)	Significant improvements in pain relief and activities of daily living with taohongsiwu versus vitamin B6
Case reports
[45]	Sorafenib	Topical clobetasol, cetirizine tablets, cold sponging	Patient able to continue on sorafenib therapy at reduced dose
[46]	BRAF inhibitors (vemurafenib or dabrafenib)	Topical steroids and keratolytics	Successful control of symptoms
[47]	Sorafenib	Narrow-band ultraviolet B phototherapy	Used to treat psoriasis but found to successfully alleviate HFSR as well Patient had first received topical urea/emollient therapy, which had been unsuccessful
[48]	Sunitinib or imatinib	Topical psoralen + ultraviolet A therapy (±methoxsalen or prednisone)	Prolonged remission of symptoms while patient remained on full-dose chemotherapy
[49]	Sorafenib	Topical corticosteroids, podiatric management, and thermal water gel	Symptom resolution with sorafenib interruption and restart at a lower dose
[50]	Sorafenib	Topical clobetasol propionate ointment	Symptom resolution without interruption of sorafenib therapy
[51]	Sorafenib	Topical prednicarbate ointment, fusidic acid cream and moisturizer (dexpanthenol)	Successful control of symptoms, allowing continuation of sorafenib treatment
[52]	Dabrafenib	Pregabalin	Patient able to stop narcotics and return to normal activities within 1 week