Hollywood, FL-At the National Comprehensive Cancer Network 20th Annual Conference, Mario E. Lacouture, MD, Associate Professor of Dermatology at Weill Cornell Medical College, and an Associate Attending Physician at Memorial Sloan Kettering Cancer Center, New York, NY, presented some clinical pearls that can guide the management of dermatologic toxicities.1
Skin Rash and Related Symptoms
Therapeutic targeting of the epidermal growth factor receptor (EGFR) commonly produces skin rashes, but other agents-including BRAF, mechanistic target of rapamycin (mTOR), and immune checkpoint inhibitors-can also produce rashes, as can some older agents, such as liposomal doxorubicin and gemcitabine.1 The following are some recommendations for the management of rashes:
- The mainstay of treatment for most rashes is topical corticosteroids; in higher grade rashes, oral corticosteroids and antibiotics may be warranted
- Healthcare professionals should 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 brand-name items with generic products
- Topical corticosteroids should be used in the form of creams and in large tubes, because the area involved is often substantial
- Rashes associated with EGFR inhibitors should be treated prophylactically; healthcare professionals should 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 approximately 50% or more compared with reactive treatment. These agents may also reduce pruritus, secondary infections, paronychia, and nondermatologic toxicities grade ≥ 4 (eg, diarrhea, neutropenia)
- Maintain a low threshold for culturing any lesion with discharge; secondary infections with a variety of organisms are common.
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 severe cases can be treated with the neurokinin-1 receptor inhibitor aprepitant. In a small study of 45 patients with refractory itching to standard pruritus treatments, aprepitant achieved relief in 91%, and pruritus recurred in only 13%.2
Approximately 15% to 25% of patients undergoing treatment with EGFR and mTOR inhibitors can have paronychia, a soft-tissue infection around the nail, as a result of nail-plate thinning and ingrowth. 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 or bleach solution can also be helpful. Grade 2 to 3 paronychia can be treated via cauterization with silver nitrate.
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," stated Dr Lacouture. Avulsion, which is usually well tolerated, can provide relief until the nail grows back, he added.
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 postinfusion.
Brittle nails also result from EGFR inhibition, and may be seen in patients with breast cancer treated with the mTOR inhibitor everolimus, or the monoclonal antibodies trastuzumab/pertuzumab. Dr Lacouture recommended painting the nails with a hydrosoluble or polyureaurethane 16% nail lacquer.
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. Dr 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 patients receiving chemotherapy3
- Use scalp cooling (ie," coldcap "during chemotherapy, which in the 1411-patient Dutch Scalp Cooling Registry study resulted in 50% of patients eliminating head covers during their last scalp cooling session,4 and in a smaller study (N = 70) prevented severe hair loss in 36% to 92% of patients, depending on the regimen5
- Apply topical minoxidil, which reduces the duration of complete hair loss by approximately 2 months.6
Another side effect of treatment with EGFR inhibitors is hirsutism of the face.1 Dr Lacouture recommends removing unwanted facial hair by threading or plucking-not with wax or depilatories.
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 the prophylactic, celecoxib 200 mg daily, reduced HFS of grade ≥ by >50% versus the control.7 Oral corticosteroids can be beneficial when HFS is caused by liposomal doxorubicin. Although they lack data, approaches that may ameliorate multikinase inhibitor-induced HFS include clobetasol foam, salicylic acid 6% cream, and lidocaine creams and patches.1
For radiation-induced dermatitis, Dr Lacouture recommended washing with soap and water. In a randomized placebo-controlled trial, mometasone furoate was also shown to significantly reduce discomfort, itching, and redness.8 Dr Lacouture did not recommend using topical nonsteroidal agents, specifically trolamine,1 petrolatum ointments, or topical moisturizers, which have not proved effective.
These management suggestions may ameliorate dermatologic toxicity, which matters to patients now more than ever, Dr Lacouture emphasized. "Improvements in survival have given patients more opportunity to worry about their appearance and quality of life."
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 23, 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;13:1020-1024.
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;3:84-91.
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;51:497-504.
5. Katsimbri P, Bamias A, Pavlidis N. Prevention of chemotherapy-induced alopecia using an effective scalp cooling system. Eur J Cancer. 2000;36:766-771.
6. Duvic M, Lemak NA, Valero V, et al. A randomized trial of minoxidil in chemotherapy-induced alopecia. J Am Acad Dermatol. 1996;35:74-78.
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;137:953-957.
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;79:1460-1466