Hand foot skin reaction in cancer patients treated with the multikinase inhibitors sorafenib and sunitinib.
BACKGROUND
This study examined clinicopathological findings and management of hand foot skin reaction (HFSR) to sorafenib and sunitinib in a dermatology referral center for cancer-related toxic effects.


METHODS
We identified 12 patients who developed HFSR in a 1-year period (2007). Medical records and histological specimens were investigated for clinicopathological data and results on management.


RESULTS
We identified 12 patients developing HFSR on treatment with sorafenib (83%) or sunitinib (17%). Majority presented with grade 3 (75%) HFSR and a median Skindex score of 43. Biopsies in seven patients showed horizontal layers of keratinocyte necrosis, which correlated to time of drug exposure: early (<30 days from initiation) leading to stratum granulosum-spinosum alterations and late (> or =30 days) resulting in stratum corneum pathology. Treatment with topical urea singly (n = 3), plus tazarotene (n = 7), or fluorouracil (n = 2) resulted in > or =2 grade improvement in the majority of patients (58%), with five patients (42%) improving one grade (P = 0.007). Median Skindex score at follow-up was 32 (P = 0.22).


CONCLUSIONS
There are unique clinicopathological characteristics of HFSR due to the multikinase inhibitors that correlate with time of agent initiation. Treatment with topical agents having keratolytic, antiproliferative, and anti-inflammatory properties showed benefit.
Department of Dermatology, SERIES Clinic, Northwestern University's Feinberg School of Medicine, Chicago, IL 60611, USA. m-lacouture@northwestern.edu
M E
ME
Lacouture
L M
LM
Reilly
P
P
Gerami
J
J
Guitart
D000287:Administration, Topical; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000009:adverse effects*; D001557:Benzenesulfonates / Q000009:adverse effects* / Q000627:therapeutic use; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy; D002292:Carcinoma, Renal Cell / Q000188:drug therapy; D005260:Female; D005472:Fluorouracil / Q000627:therapeutic use; D005533:Foot Dermatoses / Q000139:chemically induced* / Q000188:drug therapy / Q000473:pathology; D006229:Hand Dermatoses / Q000139:chemically induced* / Q000188:drug therapy / Q000473:pathology; D006801:Humans; D007211:Indoles / Q000009:adverse effects* / Q000627:therapeutic use; D007680:Kidney Neoplasms / Q000188:drug therapy; D008113:Liver Neoplasms / Q000188:drug therapy; D008297:Male; D008875:Middle Aged; D009536:Niacinamide / Q000031:analogs & derivatives; D009539:Nicotinic Acids / Q000627:therapeutic use; D010671:Phenylurea Compounds; D047428:Protein Kinase Inhibitors / Q000009:adverse effects*; D011725:Pyridines / Q000009:adverse effects* / Q000627:therapeutic use; D011758:Pyrroles / Q000009:adverse effects* / Q000627:therapeutic use; D000077157:Sorafenib; D000077210:Sunitinib; D014508:Urea / Q000627:therapeutic use; D012176:Retinoids
D000970:Antineoplastic Agents; D001557:Benzenesulfonates; D005472:Fluorouracil; D007211:Indoles; D009536:Niacinamide; D009539:Nicotinic Acids; D010671:Phenylurea Compounds; D047428:Protein Kinase Inhibitors; D011725:Pyridines; D011758:Pyrroles; D000077157:Sorafenib; D000077210:Sunitinib; D014508:Urea; C086827:tazarotene; D012176:Retinoids