As therapies improve cancer survival, oncologists will have to better manage the associated skin toxicities, according to Mario E. Lacouture, MD, a dermatologist and associate attending at the Memorial Sloan-Kettering Cancer Center in New York.
“These conditions will become even more important when the drugs you are using already in the metastatic setting enter the adjuvant setting and with dose escalation and combination studies,” he said. “And, of course, these patients are living so long with your therapies right now that there is more emphasis on survivorship issues.”
Skin issues are hardly superficial in the oncology population, Dr. Lacouture asserted. They often trigger a reduction or discontinuation of lifesaving treatment, markedly impair quality of life, threaten physical health and activities of daily living, and can be costly to treat.
With the introduction of novel targeted agents that spare normal tissues better than conventional cytotoxic chemotherapy, it was expected that skin toxicity would become less problematic, he said. However, “it turns out that blocking these proteins or pathways leads to a constellation of dermatologic adverse events that will be specific for a type of drug, depending on the target that they are blocking.”
Dr. Lacouture discussed features of some of the skin toxicities that oncologists are increasingly seeing and gave pointers for their prevention and management.
Sporadic, life-threatening cutaneous adverse events
Although it is unlikely, oncologists may encounter any of the three main classes of sporadic, life-threatening cutaneous adverse events, Dr. Lacouture said. They are the type 1 hypersensitivity reactions, mainly to platinum-based regimens and taxanes; drug rash with eosinophilia and systemic symptoms (DRESS); and the Stevens-Johnson syndrome and toxic epidermal necrolysis, which are milder and more severe forms, respectively, of the same condition, characterized by tender, erythematous skin lesions with necrosis and desquamation.
“These are unpredictable; there is no test to predict any severe reaction to any chemotherapeutic agent,” he commented. “But [they] are very rare in reviews we have conducted,” occurring in about one patient in a million each year. Unfortunately, he added, in contrast to the case with many other types of skin toxicities, with these severe forms, the drug is usually permanently discontinued.
EGFR inhibitor-induced skin toxicity
The rash triggered by epidermal growth factor receptor (EGFR) inhibitors manifests as red papules and pustules on the face and upper body and is often tender or pruritic. “Patients usually can be treated through it, if the rash is treated appropriately,” Dr. Lacouture said.
Findings in the randomized STEPP trial showed that preemptive skin treatment (moisturizer, sunscreen, a topical corticosteroid, and doxycycline) was superior to reactive skin treatment (investigator’s choice) for reducing the rate of grade 2 or higher rash and other skin toxicity in patients receiving panitumumab (Vectibix; 29% vs 62%; J Clin Oncol 2010;28:1351–1357). Another randomized trial similarly found that prophylactic oral minocycline reduced the number of skin lesions and itch when compared with placebo in patients receiving cetuximab (Erbitux; J Clin Oncol 2007;25:5390–5396).
Long-term treatment with EGFR inhibitors universally causes dry skin, which can lead to painful, paper-cut–like fissures on the fingertips and is associated with very painful paronychia or periungual inflammation in about half of patients. “The sad part about this is that patients on long-term therapy are probably those who are responding to therapy,” Dr. Lacouture commented. “And the paronychia and side effects are sometimes hindering the consistent administration of the EGFR inhibitor.”
The dry skin can be treated with ammonium lactate- or urea-containing preparations as moisturizers, he said. Zinc oxide preparations, such as Desitin, can be used for finger fissures.
The paronychia is treated with antiseptic soaks and chemical cauterization. For the former, patients simply soak their fingers and toes nightly in a solution of white vinegar, which has antibacterial and astringent properties. Chemical cauterization is performed with inexpensive silver nitrate sticks; the sticks are activated in water and some of the liquid is applied to the lateral nail fold and allowed to dry (for a demonstration, visit www.youtube.com/watch?v=HF5oopqheJY). Patients will need to do this about once a week, and usually only two to three applications are needed. The treatment is so simple that patients can be taught to do it themselves at home and so effective that it has almost abolished the need to perform nail avulsions.