The correct answer is C: A cutaneous complication directly related to sunitinib treatment.
Discussion: Sunitinib malate (Sutent), an oral, targeted multikinase inhibitor, interrupts oncogenic pathways by interfering with various tyrosine kinases, including the receptors for platelet-derived growth factor, vascular endothelial growth factor, and c-kit. Such inhibition leads to blockade of cellular proliferation, reduction of tumor-induced angiogenesis, and increase in cellular apoptosis. The drug has been approved for several years in the United States for the treatment of advanced renal cell carcinoma and gastrointestinal stromal tumors of the stomach, bowel, or esophagus; in May 2011, the agent also received US Food and Drug Administration approval for the treatment of progressive and unresectable neuroendocrine neoplasms of the pancreas (or similar tumors that have metastasized elsewhere).[2-4] While a number of serious systemic adverse events have been occasionally reported, the agent is well tolerated overall. Interestingly, hypertension, typically considered a serious adverse event, has in most cases proven to be a positive predictive factor associated with significantly longer progression-free and overall survival rates.
Because sunitinib is a close structural and functional relative of sorafenib(Drug information on sorafenib), it should not be surprising that cutaneous toxicity is seen relatively often in association with sunitinib therapy. Both sorafenib and sunitinib have these frequent skin side effects: a nonspecific maculopapular rash, hand-foot syndrome, facial erythema with or without edema, subungual splinter hemorrhages, stomatitis, alopecia, and xerosis.[5,6] However, sunitinib has also (and uniquely) been associated with hair dyspigmentation (typically graying in 10% of patients), yellowing of the skin (in up to 28% of patients), and pyoderma gangrenosum–like ulcerations (a rare finding).[6-9]
Sunitinib has additionally been reported in a prospective study to result in a severe groin (scrotum and upper, inner thigh) eruption in more than 12% of male patients. The eruption is accompanied by desquamation and mild itching. This singular drug reaction may appear as early as 2 weeks following initiation of sunitinib therapy but most often appears 9 to 10 weeks after first exposure. Positive rechallenge has verified the etiologic relationship. The eruption may improve by a decrease in dosage but does not respond well to topical therapies. Failing the aforementioned interventions, the rash clears, on average, several weeks after drug discontinuation. A similar problem has not been seen with sorafenib. In all cases, risk-benefit analysis should be considered before discontinuing this drug, especially if objective clinical response has been documented.
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