Thanks to new treatments and advances in the early diagnosis of many cancers, there are now more than 15.5 million cancer survivors alive in the US, and this number will grow to more than 20 million by 2026.1 These survivors are often left with collateral damage from their treatments. “Chemo brain,” chronic pain, and sexual dysfunction and incontinence among prostate cancer survivors have gotten a great deal of attention, but the dermatologic side effects and after effects of cancer treatment remain an orphaned area, and these side effects are not just cosmetic or nuisances.
In a survey of 350 cancer survivors, patients ranked skin irritation and dry skin as the most bothersome side effects from cancer therapy—well above insomnia, fatigue, hair loss, diarrhea, and nausea and vomiting.2
Too Few Studies
Part of the problem in managing cancer treatment side effects is that studies on interventions are few and far between, even for older therapies such as taxane-based chemotherapy. Chemotherapy-induced alopecia as well as nail and skin changes occur in up to 89 percent of patients receiving taxane-based chemotherapy through a direct cytotoxic effect. Dr. Friedman and colleagues recently performed a systematic review of 34 studies published between January 1, 1980 and August 13, 2018 to assess the efficacy and safety of interventions to prevent taxane-induced dermatologic adverse events.3 Findings show that cooling therapies such as cold caps, scalp cooling systems, frozen gloves, and frozen socks may offer the best protection against the adverse effects of taxane-based chemotherapy. Urea-based creams can be helpful for hand/foot side effects, while off-label use of topical lovastatin and systemic corticosteroids did not provide adequate protection against taxane-induced dermatologic adverse events.
Additional research is needed to establish routine protocols for cooling methods and to identify new approaches to mitigate these adverse events. In addition, the onus is on researchers to design and validate standardized outcome measures for successful hair, skin, and nail injury prevention.
Permanent Hair Loss
A good number of patients have permanent hair loss from chemotherapy. In others, even if the hair does grow back, it doesn’t look or feel the way it did before cancer. One of the most pressing questions is why. If we could identify this subgroup of patients at risk for permanent hair loss before treatment, could we do something differently to prevent it from occurring in the first place?
Fingertip soaks in a one-part white vinegar to one-part water soak twice a week may also prevent infections enabled by the early lifting of the nail plate that can occur with some treatment regimens.
We may try minoxidil (Rogaine, Johnson & Johnson Consumer) to aid in the re-growth of hair after patients have completed their treatment. There is also some emerging data that bimatoprost could be beneficial in treating chemotherapy-induced hair loss. In truth, we don’t have data on interventions that can stop this side effect and we have even less data on what to do when it occurs.
The stakes are higher today, shares Beth N. McLellan, MD, the Director of Oncodermatology at Montefiore Medical Center in the Bronx, NY. “In the past, cancer patients weren’t living as long, and they were sicker, but with better treatments, patients are living longer,” she says. “When a patient with early stage breast cancer loses her hair, she has a very long life ahead of her, so side effects, such as permanent hair loss, become more problematic.”
Hands and Feet
Hand-foot skin reaction (HFSR) is one of the most common cutaneous side effects of cancer, affecting up to 62 percent of patients on targeted therapies. It is associated with multikinase inhibitors, such as sorafenib, sunitinib, pazopanib, and bevacizumab, that specifically target the VEGF pathways implicated in angiogenensis, a process that provides the blood supply critical for development and invasive potential of many solid tumors, notably in advanced renal cell carcinoma and hepatocellular carcinoma. HFSR clinically appears within six weeks of treatment initiation, and most commonly within the first two to four weeks. It typically presents as tender, hyperkeratotic plaques surrounded by a peripheral halo of erythema and is sometimes accompanied by superficial blistering and callus formation. It is important to distinguish between HFSR, as described here, and the hand-foot syndrome (HFS) reported with conventional cytotoxic therapies, such as cytarabine, doxorubicin, capecitabine, and 5-fluorouracil. HFS presents as diffuse symmetric paresthesias, erythema, and edema that localizes to flexural surfaces with associated pain and tenderness. HFSR, in contrast, is characterized by the localized hyperkeratotic lesions with surrounding erythema as detailed above.4
Cooling therapies such as cold caps, scalp cooling systems, frozen gloves, and frozen socks may offer the best protection against the adverse effects of taxanebased chemotherapy. Urea-based creams can be helpful for hand/foot side effects.
While treatment recommendations are scarce, there is some data supporting both active and prophylactic therapies. A randomized trial using a prophylactic urea-based cream in hepatocellular carcinoma patients treated with sorafenib found that those treated had decreased all grades of HFSR from 73.6 percent to 56 percent and delayed onset of HFSR from 34 days to 84 days.5 (Treatment recommendations for each stage of HFSR are shown in Table 1.6)
Skin changes caused by ionizing radiation, known as radiation dermatitis, have been scientifically documented for more than a century and occur in about 95 percent of patients receiving radiation therapy for cancer. The severity ranges from mild erythema to moist desquamation and ulceration. Despite continual improvements utilizing innovative imaging techniques, skin injury remains a significant and expected problem. Sadly, the recommendation for years has simply been “wash with mild soap,” which is frankly absurd.
It is important to distinguish between HFSR (See main text) and the hand-foot syndrome (HFS) reported with conventional cytotoxic therapies, such as cytarabine, doxorubicin, capecitabine, and 5-fluorouracil.
Amifostine has emerged as a systemic preventive treatment for the management of generalized (think dirty bomb) acute exposure, whereas pentoxifylline has been shown to reduce late sequela of radiation exposure. In 2011, evidence-based guidelines for skincare management in radiation therapy were published, which included the following:
1.) wash/bathe with lukewarm water and mild soap,
2.) use fragrance-free, lanolin-free, moisturizing cream, and
3). intensity-modulated radiation therapy.7,8,9
At the George Washington Medical Faculty Associates Supportive Oncodermatolgy Clinic, our anecdotal protocol includes pretreating the field of radiation with a class 1 steroid daily starting three days prior to initating therapy for three weeks, then reducing frequency to every other day. This is supplemented typically with a 510k device indicated for radiation dermatitis (these include Hylatopic, Textrix, Biafine, and Luximend) though coverage of these has made access difficult. Minimal soap use is advisable, but applying moisturizer to damp skin with higher frequency is missing from the recommendations.
Severe Acne-like Rashes
Patients on targeted EGFR inhibitors can develop a papulopustular eruption that looks like severe acne on the scalp, head, neck, and chest. This can be exceedingly disabling. There is some data showing that if you are about to start on one of these agents, sun protection, mild topical steroids and oral doxycycline (100mg/twice a day) can prevent this reaction without sacrificing efficacy. Dr. Friedman has had great success with more severe cases with low-dose isotretinoin (0.5mg/kg/day). Studies are ongoing to better identify preventive and active treatment strategies
Cancer patients stay on these targeted medications for as long as they continue to work. “A rash may not be bad for three weeks but when it lasts three years, it becomes much more impactful,” Dr. McClellan says. Moreover, side effects tell us that patients will respond to a drug, so it is better to continue the medications to control the cancer and manage side effects.
The Dermatologist’s Expanding Role
Dermatologists should be a part of the treatment team for cancer patients, ideally during the early planning stages. Certain interventions can stop expected side effects before they start. In some cancer centers, patients participate in education classes to learn what to expect during treatment. Nutritionists, nurses, and other healthcare professionals routinely speak to these patients and provide them with tips and tools to prevent and cope with treatment side effects. Dermatologists should also be invited to these sessions.
In a recent edition of Ask an Expert, Beth McLellan, MD, Director, Oncodermatology, Montefiore Center for Cancer Care, spoke with host Adam J. Friedman, MD about oncodermatology advances. Watch now at DermTube.com/series/ask-an-expert/
There are things that cancer patients can do to protect their skin, hair, and nails during and after cancer treatment. This list includes photoprotection, as a lot of these medications increase sun sensitivity. We recommend using high SPF, broad-spectrum sunscreen on exposed skin every day.
Skin is often an innocent bystander and can become brittle, cracked, itchy, and painful after many cancer treatments. Good moisturization applied to damp, not dry skin, can help. We also recommend using mild or no soap except in the underarm and groin areas, keeping a humidifier running in the bedroom, and using a keraloytic therapy such as urea to remove dead skin.
These individuals are at high risk for infections, so counseling on good skin hygiene is essential. Fingertip soaks in a one-part white vinegar to one-part water soak twice a week may also prevent infections enabled by the early lifting of the nail plate that can occur with some treatment regimens.
The ultimate goal is to keep patients on their life-saving cancer therapy while mitigating any vexing dermatologic side effects. Although this field is in its infancy, things are moving forward and there are a growing number of dermatologists who are interested in this area. Hopefully we will soon have more answers than we do questions.
1. American Cancer Society and National Cancer Institute. Number of US Cancer Survivors Expected to Exceed 20 Million by 2026. https://www.cancer.org/latest-news/report-number-of-cancer-survivors-continues-to-grow.html
2. Lacoutre M, et al. “Quality of life in patients with dermatologic toxicities: Experience from the SERIES clinic.” (2011), Journal of Clinical Oncology 29(15_suppl):9104-9104
3. Friedman A, et al. “Evaluation of Prevention Interventions for Taxane-Induced Dermatologic Adverse Events: A Systematic Review.” (2018). JAMA Dermatol. 2018 Dec 1;154(12):1465-1472.
4. Gomez P, Lacouture ME. “Clinical presentation and management of hand-foot skin reaction associated with sorafenib in combination with cytotoxic chemotherapy: experience in breast cancer.” (2011) Oncologist. 16(11):1508-1519.
5. Ren Z, et al. “Randomized controlled trial of the prophylactic effect of urea-based cream on sorafenib-associated hand-foot skin reactions in patients with advanced hepatocellular carcinoma.” (2015) J Clin Oncol. 2015;33(8):894-900.
6. McLellan B, Kerr H. “Cutaneous toxicities of the multikinase inhibitors sorafenib and sunitinib.” (2011) Dermatol Ther24(4):396-400.
7. Salvo N, et al. “Prophylaxis and management of acute radiation-induced skin reactions: a systematic review of the literature.” (2010) Curr Oncol 17:94–112
8. Muller K, Meineke V (2010) Advances in the management of localized radiation injuries. Health Phys 98:843–50
9. McQuestion M (2011) Evidence-based skin care management in radiation therapy: clinical update. Semin Oncol Nurs 27:e1–7