EGFR inhibitors can also cause thinning of scalp hair and, paradoxically, facial hirsutism. It is important that women be advised not to use chemical depilatories to remove the facial hair because they may experience severe burns related to drug-induced skin atrophy. “Of all the side effects, perhaps the only one that your patients will be thankful for is trichomegaly of the eyelashes,” he commented. But these long, curly eyelashes sometimes grow into the eye, causing corneal erosions and ulcerations. “So I ask all patients on EGFR inhibitors if they are having any eye complaints,” he said.
Some 38% of patients treated with EGFR inhibitors develop secondary skin infections as a result of skin toxicity (J Natl Cancer Inst 2010;102:47–53). “In other words, they have a complication of a complication,” Dr. Lacouture observed. These infections can be odd ones, too, such as fungal infections of the face or gram-negative cellulitis. “I highly recommend [you have culture swabs in your office] because I have been surprised by the kinds of organisms I recover from patients that are pathogens,” he said.
mTOR inhibitor-induced skin toxicity
Patients treated with inhibitors of the mammalian target of rapamycin (mTOR), such as everolimus (Afinitor) and temsirolimus (Torisel), may develop a nonspecific erythematous rash that is intensely pruritic. “I feel it’s very difficult to treat, very different [from] the rash you see with EGFR inhibitors,” Dr. Lacouture said. “It is so pruritic in these patients that you have to treat them with oral steroids, high-potency topical steroids, antihistamines, GABA agonists such as pregabalin (Lyrica) or gabapentin, or even doxepin.”
In addition, the mTOR inhibitors can produce a painful mucositis with ulcer-like lesions that is distinctly different from that seen with cytotoxic chemotherapy (Cancer 2010;116:210–215). It is “a completely new type of entity…more like canker sores or aphthous stomatitis,” he explained. This mucositis responds well to high-potency topical steroids.
Hand-foot syndrome
The multitargeted tyrosine kinase inhibitors (TKIs) sorafenib (Nexavar), sunitinib (Sutent), and pazopanib (Votrient) can all cause a hand-foot syndrome characterized by painful blisters on the palms and soles. It differs from that seen with fluoropyrimidines or anthracyclines in that it produces diffuse swelling, Dr. Lacouture said.
“Sorafenib appears to be the [biggest] culprit here,” he commented. The rate of high-grade hand-foot syndrome is about 9% with sorafenib, compared with roughly 6% with sunitinib and 1% with pazopanib. Management consists of high-potency topical steroids and analgesics.
When it comes to reducing the hand-foot syndrome associated with cytotoxic chemotherapy, randomized trials have found vitamin B6 (pyridoxine) to be ineffective, Dr. Lacouture noted. But dexamethasone started the day before infusion is effective in patients receiving pegylated doxorubicin (Doxil). And the nonste¬roidal anti-inflammatory drug celecoxib (Celebrex) is effective in patients receiving capecitabine (Xeloda).
Taxane-induced nail toxicity
Taxanes, especially docetaxel (Taxotere), produce some type of nail alteration in most patients, including subungual hemorrhage followed by onycholysis in some cases. “They are grade 2 and associated with pain in about a third of all treated patients,” Dr. Lacouture noted.
A quarter of patients develop a secondary infection with pathogens such as Pseudomonas, which gives their nails a green tinge due to the pyocyanin it produces. This complication can be treated with antibiotics and vinegar soaks. But better yet, nail toxicity can largely be prevented from the get-go with use of cooling gloves during the taxane infusion. In one study, for example, the rate of grade 2 nail toxicity was 22% in patients’ unprotected control hands, but 0% in their frozen glove-protected hands (J Clin Oncol 2005;23:4424–4429).
“So this is something that we have instituted,” he commented. “In the absence of these cold gloves, we just have the patients hold ice packs during the infusion to try to minimize the blood flow, [thereby limiting] the delivery of docetaxel to the nails.”
Radiation dermatitis
A persistent misconception is that radiation dermatitis is a drying of the skin, Dr. Lacouture said. “It is not really a drying, as you have apoptosis and death of skin cells, and that’s why you see the desquamation.” In fact, six trials in patients with head and neck or breast cancer have shown that trolamine (Biafine), a topical emulsion, does not prevent or reduce the severity of radiation dermatitis (Curr Oncol 2010;17:94–112). “Biafine is not effective; it hasn’t been shown to be effective in any of these studies,” he stressed. “However, it is still widely used for some reason.”