Prospective study of the cutaneous adverse effects of sorafenib, a novel multikinase inhibitor.
OBJECTIVE
To provide an accurate description and to evaluate the incidence and severity of cutaneous reactions induced by sorafenib tosylate, a new oral multikinase inhibitor.


METHODS
Double-blind, prospective dermatologic substudy performed on all consecutive patients included in our center in a large phase 3 trial.


METHODS
Institutional practice at the Gustave Roussy Institute.


METHODS
Eighty-five patients with renal cell cancer treated between November 1, 2003, and February 28, 2005. Interventions Patients were randomized to receive either sorafenib (n = 43) or placebo (n = 42). Dermatologic examination was performed before treatment, every 3 weeks during the first 4 cycles, and every 4 weeks thereafter.


METHODS
Incidence and severity of cutaneous reactions to sorafenib.


RESULTS
Thirty-nine patients (91%) experienced at least 1 cutaneous reaction in the sorafenib group vs 3 (7%) in the placebo group. A hand-foot skin reaction that appeared to be clinically distinct from the well-known chemotherapy-induced hand-foot syndrome was observed in 26 patients receiving sorafenib (60%). Reversible grade 3 hand-foot skin reaction was documented in 2 patients receiving sorafenib and led to a dose reduction. Other cutaneous reactions were facial erythema, scalp dysesthesia, alopecia, and subungual splinter hemorrhages.


CONCLUSIONS
Sorafenib induces frequent cutaneous adverse events, some of which may lead to a dose reduction. Close collaboration between oncologists and dermatologists is needed to improve both the characterization and the management of these side effects. Appropriate patient education before the initiation of therapy and the introduction of early symptomatic measures may improve management.
Autier
Julien
J
Dermatology Unit, Gustave Roussy Institute, 39 rue Camille Desmoulins, 94805 Villejuif Cedex, France.
Escudier
Bernard
B
Wechsler
Janine
J
Spatz
Alain
A
Robert
Caroline
C
D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects*; D001557:Benzenesulfonates / Q000008:administration & dosage / Q000009:adverse effects*; D002292:Carcinoma, Renal Cell / Q000188:drug therapy; D004311:Double-Blind Method; D003875:Drug Eruptions / Q000453:epidemiology* / Q000209:etiology / Q000473:pathology; D005260:Female; D005533:Foot Dermatoses / Q000139:chemically induced; D005602:France / Q000453:epidemiology; D006229:Hand Dermatoses / Q000139:chemically induced; D006801:Humans; D015994:Incidence; D007680:Kidney Neoplasms / Q000188:drug therapy; D008297:Male; D008875:Middle Aged; D009536:Niacinamide / Q000031:analogs & derivatives; D010671:Phenylurea Compounds; D011446:Prospective Studies; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects*; D011725:Pyridines / Q000008:administration & dosage / Q000009:adverse effects*; D012720:Severity of Illness Index; D000077157:Sorafenib
D000970:Antineoplastic Agents; D001557:Benzenesulfonates; D010671:Phenylurea Compounds; D047428:Protein Kinase Inhibitors; D011725:Pyridines; D009536:Niacinamide; D000077157:Sorafenib