The correct answer is C: A cutaneous complication directly related to sunitinib treatment.
A 56-year-old man with renal cell carcinoma developed widely metastatic disease post nephrectomy, for which he was receiving cyclic sunitinib therapy (50 mg daily for 4 weeks, followed by a 2-week rest period). Toward the end of his second cycle of therapy, he developed minimally pruritic, bright red erythema and fine scale involving both sides of the scrotum. Potassium hydroxide(Drug information on potassium hydroxide) preparation and culture were both negative for Candida species, and a Wood's lamp examination ruled out erythrasma. Aside from concerns about this eruption, the patient was tolerating the sunitinib well and had no other relevant complaints. Family history, past medical history, and social history were unremarkable or not pertinent.
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.[1] 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.[5] 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.[10] 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.[10] 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.
References
1. Izzedine H, Buhaescu I, Rixe O, et al. Sunitinib malate. Cancer Chemother Pharmacol. 2007;60:357–364.
2. Powles T, Chowdhury S, Jones R, et al. Sunitinib and other targeted therapies for renal cell carcinoma. Br J Cancer. 2011;104:741–745.
3. Blay JY. Pharmacological management of gastrointestinal stromal tumors: An update on the role of sunitinib. Ann Oncol. 2010;21:201–215.
4. Raymond E, Dahal L, Raoul JL, et al. Sunitinib malate for the treatment of pancreatic neuroendocrine tumors. N Engl J Med. 2011;364:501–513.
5. Lee WJ, Lee JL, Chang SE, et al. Cutaneous adverse effects in patients treated with the multitargeted kinase inhibitors sorafenib and sunitinib. Br J Dermatol. 2009;161:1045–1051.
6. Autier J, Mateus C, Wechsler J, et al. Cutaneous side effects of sorafenib and sunitinib. Ann Dermatol Venereol. 2008;135:148–153.
7. Wollenberg A, Staehler M, Eames T. Cutaneous side effects of the multikinase inhibitors sorafenib and sunitinib. Hautarzt. 2010;61:662–667.
8. McLellan B, Kerr H. Cutaneous toxicities of the multikinase inhibitors sorafenib and sunitinib. Dermatol Ther. 2011;24:396–400.
9. Nadauld LD, Miller MB, Srinivas S. Pyoderma gangrenosum with the use of sunitinib. J Clin Oncol. 2011;29:e266–267. (E-pub Jan 10, 2011)
10. Billemont B, Barte S, Rixe O. Scrotal cutaneous side effects of sunitinib. N Engl J Med. 2008;359:975–976.
