Cutaneous squamous cell carcinoma and inflammation of actinic keratoses associated with sorafenib.
BACKGROUND
Sorafenib-induced dermatologic toxicity is common and consists primarily of dry skin, maculopapular rash, hand-foot skin reaction, and alopecia. Cutaneous squamous cell carcinoma (SCC) and inflammation of actinic keratosis (AK) were reported in 2 patients treated with sorafenib (Lacouture et al), but the scope of this observation has not been evaluated.


METHODS
We reviewed medical records of 131 patients with metastatic renal cell carcinoma treated with single-agent sorafenib at our institution from June 1, 2005, through April 4, 2007.


RESULTS
We identified 7 cases of cutaneous SCC, 2 cases of SCC keratoacanthoma type, 2 cases of focal squamous atypia, and 3 cases of AKs. The time to development of SCC or AK from the start of sorafenib was 9.3 months (median, 6.5 months; range, 0.9-43 months). Ten of these 14 patients discontinued therapy with sorafenib: 7 patients as a result of disease progression, 2 patients as a result of nondermatologic toxicity, and 1 patient as a result of dermatologic toxicity. Four patients are continuing sorafenib therapy at reduced doses because of diarrhea and fatigue. One patient receiving sorafenib at a 25% dose reduction developed a second invasive SCC lesion on his forearm 6 months after the initial resection.


CONCLUSIONS
These data suggest that there could be an association between sorafenib therapy and the development of cutaneous SCC and inflammation of AK. This adverse event has important therapeutic implications. Full appraisal of this observation in prospective studies is warranted.
Dubauskas
Zita
Z
Department of Genitourinary Medical Oncology, The University of Texas Health Science Center, Houston, TX 77030, USA.
Kunishige
Joy
J
Prieto
Victor G
VG
Jonasch
Eric
E
Hwu
Patrick
P
Tannir
Nizar M
NM
D000368:Aged; D001557:Benzenesulfonates / Q000009:adverse effects*; D002292:Carcinoma, Renal Cell / Q000188:drug therapy; D002294:Carcinoma, Squamous Cell / Q000139:chemically induced* / Q000473:pathology; D003875:Drug Eruptions / Q000209:etiology*; D005260:Female; D006801:Humans; D007249:Inflammation / Q000139:chemically induced / Q000473:pathology; D007636:Keratoacanthoma / Q000139:chemically induced / Q000473:pathology; D055623:Keratosis, Actinic / Q000139:chemically induced* / Q000473:pathology; D007680:Kidney Neoplasms / Q000188:drug therapy; D008297:Male; D008875:Middle Aged; D009536:Niacinamide / Q000031:analogs & derivatives; D010671:Phenylurea Compounds; D047428:Protein Kinase Inhibitors / Q000009:adverse effects*; D011725:Pyridines / Q000009:adverse effects*; D012878:Skin Neoplasms / Q000139:chemically induced* / Q000473:pathology; D000077157:Sorafenib
D001557:Benzenesulfonates; D010671:Phenylurea Compounds; D047428:Protein Kinase Inhibitors; D011725:Pyridines; D009536:Niacinamide; D000077157:Sorafenib