Managing Dermatologic Toxicities

TON May 2015 Vol 8 No 3

Oncology nurses are tasked with helping patients with cancer manage the toxicities of their treatment. With the advent of targeted therapies, this challenge has become greater. At the National Comprehensive Cancer Network (NCCN) 20th Annual Conference, Mario E. Lacouture, MD, one of the foremost experts in dermatologic toxicities, presented some clinical pearls that can guide management of these toxicities.1

Lacouture is Associate Professor of Dermatology at Cornell University and Associate Member of Memorial Sloan Kettering Cancer Center, New York.

Skin Rash and Related Symptoms

Therapeutic targeting of the epidermal growth factor receptor (EGFR) commonly produces skin rash (Figure 1), but other agents—including BRAF, mTOR, and immune checkpoint inhibitors—can also produce rash, as can some older agents, such as liposomal doxorubicin and gemcitabine. Lacouture made these recommendations for managing rash:
• Mainstay of treatment for most rashes is topical corticosteroids; in higher grades of rash, oral corticosteroids and antibiotics may be warranted.
• For ease of prescribing, become familiar with the brand name of one low-potency corticosteroid (to be used on the face and intertriginous areas) and one high-potency corticosteroid (to be used safely on other parts) and use those routinely; the pharmacist can substitute the generic.
• Prescribe topical corticosteroids in the form of creams, and in large tubes, since the involved area is often substantial.
• Treat rash associated with EGFR inhibitors prophylactically; do not wait for symptoms to appear.
• Evidence supports the prophylactic use of oral minocycline and doxycycline, which have been shown to reduce rash severity by about 50% or more, compared to “reactive” treatment. These agents may also reduce pruritus, secondary infections, and paronychia as well as nondermatologic toxicities grade 3 or higher (diarrhea, neutropenia, etc).
• Maintain a low threshold for culturing any lesion with discharge; secondary infections with a variety of organisms are common.

FigFigure 1

Xerosis (dry skin) often occurs further along in the treatment course. Moisturizing is best accomplished with creams that contain ammonium lactate, salicylic acid, or urea.
Pruritus usually responds to oral antihistamines and topical corticosteroids, but when severe it can be treated with the NK1 receptor inhibitor aprepitant. In a small study of patients whose itching was refractory to standard pruritus treatments, aprepitant achieved relief in 91% and itching recurred in only 13%.2

Nail Changes

Approximately 15% to 25% of patients undergoing treatment with EGFR and mTOR inhibitors can develop paronychia, a soft-tissue infection around the nail, as a result of nail-plate thinning and ingrowth. (See Figure 2.) Local treatment depends on paronychia severity. Mild cases can be treated with topical therapies; if there is discharge and a documented infection, an oral antibiotic is warranted. Soaking nails in a vinegar/water solution can also be helpful. Grade 2-3 paronychia can be treated via cauterization with silver nitrate.

FigFigure 2

When patients do not respond to these measures, partial or complete nail avulsion (removing the nail plate) may be warranted. “This is initially scary to patients, but they are often very relieved after we do this,” Lacouture noted. Avulsion, which is usually well tolerated, can provide relief until the nail grows back, he said.

The nail changes induced by treatment with taxanes (especially docetaxel) are different from those induced by EGFR and mTOR inhibitors; elevation of the nail plate, inflammation, and sometimes bleeding and infection are seen. Severe nail changes can often be prevented by having the patient grip ice bags for 15 minutes before infusion, during treatment, and 15 minutes post infusion.

Brittle nails are also a consequence of EGFR inhibition, and they also may be seen in patients with breast cancer being treated with the mTOR inhibitor everolimus or the monoclonal antibodies trastuzumab/pertuzumab. Lacouture recommended painting the nails with a hydrosoluble nail lacquer or the prescription product poly(urea-urethane) 16%.

Alopecia and Facial Hirsutism

Alopecia is a well-established side effect of numerous cytotoxic agents, but hair thinning can also occur with BRAF, MEK, EGFR, and hedgehog inhibitors. Lacouture made the following recommendations to prevent or manage hair loss:
• Use bimatoprost for eyelash alopecia, which has been shown to increase length and thickness of eyelashes in chemotherapy patients.3
• Use scalp cooling (ie, “cold cap”) during chemotherapy, which in the 1400-patient Dutch Scalp Cooling Registry study allowed 50% of patients to eliminate head covers,4 and in a smaller study (N=70) prevented severe hair loss in 36% to 92% of patients (depending on the type of regimen).5
• Apply topical minoxidil, which reduces the duration of complete hair loss in patients by approximately
2 months.6

Another side effect of treatment with EGFR inhibitors is hirsutism of the face. Lacouture recommends removing unwanted facial hair by threading or plucking—not with waxing or depilatories.

Other Toxicities

Hand-foot syndrome (HFS) can be seen with a variety of drugs, and its manifestations can differ by drug class. The only randomized study of HFS prevention, conducted in patients receiving capecitabine, showed that prophylactic celecoxib 200 mg/day reduced HFS of grade 2 or higher by more than 50% versus control.7 Oral corticosteroids can be beneficial when HFS is due to liposomal doxorubicin. Though less supported by research, approaches that may ameliorate HFS induced by multikinase inhibitors include clobetasol foam, salicylic acid 6% cream, and lidocaine creams and patches.

For radiation-induced dermatitis, Lacouture recommended washing with soap and water. The medium-strength topical corticosteroid mometasone was also shown, in a randomized placebo-controlled trial, to significantly reduce discomfort, itching, and redness.8 Lacouture did not recommend using topical nonsteroidal agents (trolamine), petrolatum ointment, or topical moisturizers, which have not proven effective.

These management suggestions may ameliorate dermatologic toxicity, which matters to patients now more than ever, Lacouture emphasized. Improvements in survival, he noted, “have given patients more opportunity to worry about their appearance and quality of life.”

References

1. Lacouture ME. Management of dermatologic toxicities associated with targeted therapies. Presented at: National Comprehensive Cancer Network 20th Annual Conference; March 12-14, 2015; Hollywood, FL. http://nccnac2015.conferencespot.org/59242-nccn-1. 1948867/t-001-1.1948953/f-001-1.1948954/a-013-1.
1948958. Accessed April 5, 2015.
2. Santini D, Vincenzi B, Guida FM, et al. Aprepitant for management of severe pruritus related to biological cancer treatments: a pilot study. Lancet Oncol. 2012;13
(10):1020-1024.
3. Morris CL, Stinnett S, Woodward J. The role of bimatoprost eyelash gel in chemotherapy-induced madarosis: an analysis of efficacy and safety. Int J Trichology. 2011;3(2):84-91.
4. van den Hurk CJ, Peerbooms M, van de Poll-Franse LV, et al. Scalp cooling for hair preservation and associated characteristics in 1411 chemotherapy patients—results of the Dutch Scalp Cooling Registry. Acta Oncol. 2012;51(4):497-504.
5. Katsimbri P, Bamias A, Pavlidis N. Prevention of chemotherapy-induced alopecia using an effective scalp cooling system. Eur J Cancer. 2000;36(6):766-771.
6. Duvic M, Lemak NA, Valero V, et al. A randomized trial of minoxidil in chemotherapy-induced alopecia. J Am Acad Dermatol. 1996;35(1):74-78.
7. Zhang RX, Wu XJ, Lu SX, et al. The effect of COX-2 inhibitor on capecitabine-induced hand-foot syndrome in patients with stage II/III colorectal cancer: a phase II randomized prospective study. J Cancer Res Clin Oncol. 2011;137(6):953-957.
8. Miller RC, Schwartz DJ, Sloan JA, et al. Mometasone furoate effect on acute skin toxicity in breast cancer patients receiving radiotherapy: a phase III double-blind, randomized trial from the North Central Cancer Treatment Group N06C4. Int J Radiat Oncol Biol Phys. 2011;79(5):1460-1466.

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