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Novel palliative anticancer therapies, including targeted agents, cause dermatologic toxicities that impact patients' functional status and quality of life. As the frequency in utilization of targeted agents in palliative and hospice care settings increases, so does the need for nurses to maintain knowledge and expertise on the management of treatment-induced dermatologic toxicities. The purpose of this review was to describe cancer treatment-related dermatologic toxicities through a case presentation and describe strategies for prevention, assessment, and management of the symptoms in palliative care settings. Vigilance in assessment, prevention, and management of symptomatic dermatologic toxicities is critical to improving patient care. Palliative care nurses can improve patient care through counseling, education, and support. Early identification of symptomatic dermatologic toxicities can facilitate treatment in a timely fashion. Palliative care nurses can play an integral role in symptom management related to dermatologic toxicities for cancer patients receiving targeted therapies.
Over the last decade, the development of new systemic cancer therapies has shifted away from the traditional chemotherapy agents toward targeting specific pathways involved in carcinogenesis. Although targeted therapies are less likely than traditional chemotherapeutic agents to cause systemic adverse effects, dermatologic toxicities are much more common with these agents. The majority of these novel agents are used in advanced, metastatic disease settings, and many cancer patients may still be receiving palliative treatments at the end of life. Therefore, cancer patients at the end of life are expected to experience adverse effects from targeted therapies as disease treatment continues near the end of life. As the number and utilization of targeted therapies increase in palliative and hospice care settings, so does the need for palliative care nurses to assess and recognize the dermatologic adverse effects of these agents. The purpose of this review was to describe cancer treatment-related dermatologic toxicities through a case presentation and describe strategies for prevention, assessment, and management of the symptoms in palliative and hospice care settings.
Since the approval of the first targeted therapy by the Food and Drug Administration in 2003, several targeted agents have been tested and approved for the management of non-small cell lung, colon, pancreatic, head and neck squamous cell, and breast cancers. These agents include erlotinib, cetuximab, lapatinib, and panitumumab. Incidences for dermatologic toxicities are frequent, with approximately 30% to 80% of patients affected while receiving targeted therapy treatments.1 Severe, dermatologic adverse effects may result in 36% of patients receiving dose modifications or 72% being discontinued from treatment.1
Targeted therapies are associated with dermatologic adverse effects that result in significant physical and emotional discomfort for patients in palliative care settings.1-3 The molecular mechanisms of these adverse effects are not fully understood but may be related to the inhibition of multiple pathways that are essential to normal growth and development.4,5 Clinical characteristics are similar but have unique differences depending on the type of agent used as well as the target. Dermatologic toxicities are often characterized by the degree, location, symptoms, and type of skin lesion.6Table 1 presents a list of common dermatologic toxicities secondary to targeted therapies. Papulopustular rash is a common dermatologic characteristic and affects up to 30% to 80% of patients.8 Patients are at risk for secondary infections at the rash sites, with 38% developing bacterial infections, 29% with viral infections, and approximately 10% with fungal infections.6 Patients often refer to the rash as acne, although the papulopustular rash is distinct from acne.7 Skin rash typically begins within 8 to 10 days after treatment initiation, peaks at 2 weeks, and diminishes within 8 weeks of treatment discontinuation.7,9 Erythema and edema on the central face with a sensation of sunburn may also occur (also known as sensory disturbance).7 The papulopustular rash eventually dries off and forms crusts. Long-term effects after treatment may include telangiectasia (abnormal dilation of capillary blood vessels leading to visible dermatologic changes) and diffuse erythema in the previously affected areas.7,10 Xerosis and pruritus are also common, occurring in approximately 10% to 52% of patients. With the constant scratching secondary to pruritus, patients are at risk for superinfections with microorganisms such as Staphylococcus aureus.7
Nail changes, such as diminished growth, painful paronychia (inflammation of the folds of tissue surrounding the nail), swelling and fissuring of lateral nail folds, and cracking of the nails and cuticles, affect approximately 12% to 16% of patients.7 Paronychia primarily affects the fingernails (thumb) and toenails (big toe) and is often associated with pain. It occurs later than skin rash, between 20 days and 6 months of treatment.11-13 Patients are also at risk for surperinfections, particularly when fissures and cracks in the nails appear.
Hair changes are also seen with targeted therapies, particularly those agents that target epidermal growth factor receptors (EGFRs) (ie, erlotinib). This is primarily because EGFR is expressed in keratinocytes in the epidermis and hair follicles. Approximately 30% of patients will report hair changes after about 100 days of treatment, and the changes manifest as alopecia in the scalp and body.1,7 Patients also often report changes in hair texture (curlier, finer, and brittle), which may reverse after treatment.7 Approximately 20% of patients will have hypertrichosis and trichomegaly, where the eyelashes grow long and curly and turn inward.14 Skin lesions on the scalp can result in alopecia, and in areas where significant scarring occurs, the hair may not grow back.6
Hand-foot skin reaction (HFSR) is the most common dermatologic adverse manifestation for targeted agents such as sorafenib. It is similar to hand-foot syndrome seen with antineoplastic therapy (palm plantar distribution, tenderness, dose dependency) but has distinct clinical and histological features.15 Lesions in HFSR are scaling and erythematic and are localized in areas of pressure (tips of finger and toes, heels, and metacarpophalangeal or interphalangeal joints).16 The lesions are usually followed by areas of thickened or hyperkeratotic skin after several weeks, which can be painful and impairs function.16 For the majority of patients, HFSR develops within the first 2 to 4 weeks of administration, and incidence rates based on clinical trial data were 33.8% for Grades 1 to 3 and 8.9% for Grade 3.15-17
The current literature provides some evidence that documents the impact of dermatologic toxicities on overall quality of life (QOL) for patients receiving palliative targeted therapy. Skin rash impacts psychological well-being by causing anxiety, depression, and fears about the symptoms worsening, and higher severity is associated with greater decrements in QOL.18 Physical discomfort, such as pain, burning, and skin sensitivity, is burdensome for patients and may significantly restrict daily activities and independence.19 Patients also report experiencing worry, frustration, depression, and withdrawal from social activities secondary to dermatologic toxicities.19,20 Younger patients (<50 years) are more likely than older patients to report diminished dermatology-related QOL.20 Patients are also significantly impacted by HFSR, with pain, irritation, and persistence of skin condition rated as the most troublesome for patients.21
It is important for palliative care nurses to remember that dermatologic toxicities can impact QOL. Hence, assessment, prevention, and prompt management are key to maintaining patients' function and QOL while receiving palliative target therapies. In clinical settings, treatment-related toxicities are often graded by level of severity. One of the most commonly used toxicity grading system in cancer is the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE). However, many have suggested that the CTCAE was not designed specifically for targeted therapy-induced dermatologic toxicities and may result in underreporting or poor grading.22 Recently, the Multinational Association of Supportive Care in Cancer (MASCC) Skin Toxicity Study Group proposed the use of a more class-specific grading scale for standardizing assessment of treatment-related dermatologic toxicities.22,23 The grading scale is divided into four grading levels, with Grade 1 equivalent to having the least amount of toxicity.22 Although the MASCC scale shows promise, there is still only preliminary evidence to support its reliability, and to date, no other evidence-based assessment tool is available specifically for targeted therapy-induced dermatologic toxicities. The Skindex 16, a dermatology-specific QOL instrument, was developed to assess dermatologic toxicity-related QOL.24 Besides the use of clinical toxicity grading scales, nurses should assess and document the degree and location of the toxicities. Most importantly, nurses should assess how much the dermatologic adverse effects affect patients' QOL and function.25,26
Table 2 presents prevention and management strategies for targeted therapy-induced dermatologic toxicities. To date, the majority of strategies are anecdotal, although in recent years more promising evidence revealed options for the management of dermatologic toxicities. The goal of management should be focused on patients' QOL through aggressive symptom management.
The treatment of skin rash is largely based on anecdotes, and currently recommendations vary across institutions. The most conventional topical antiacne medications such as topical retinoids and benzoyl peroxide are not indicated to treat papulopustular skin rash.12,28,29 These agents are drying and may exacerbate burning sensations and irritation.27 Preventive measures (Weeks 1-6 following treatment initiation) include the following: (1) topical hydrocortisone 1% cream with moisturizer and sunscreen twice daily and (2) systemic antibiotics (ie, doxycycline 100 mg daily).1 For treatment, topical steroids and antibiotics (clindamycin, erythromycin) may be useful for treating papulopustular skin rash.7,27 Systemic therapy is an option in settings where rash is severe (Grade 3 or 4), infections occur, when rash is refractory to topical treatments, and when rash is recurrent despite treatment modifications.7 Oral antibiotics such as tetracycline, doxycycline, or minocycline are viable options.18 Xerosis and pruritus treatment is reactive and symptom directed. At treatment initiation for prevention purposes, patients should be instructed on dry skin care such as using tepid water for bathing and washing, using oil-in-water moisturizers and emollients, avoiding extreme temperatures and direct sunlight, and avoiding drying agents such as alcohol-based lotions.1,7,11,27 Topical steroids can be used in severe cases of xerosis.
For paronychia, fissures, and nail changes, patients should be instructed at treatment initiation to avoid wearing tight shoes that create pressure that increases friction, avoid frequent water immersion and harsh chemicals, and apply emollients frequently to the periungal soft tissue. Bleach and vinegar soaks can be used daily to provide symptomatic relief and prevent superinfections.27 Liquid glues or cyanoacrylate can be used to seal cracks and fissures. Topical corticosteroids may be helpful in severe cases.1,11 Trichomegaly is associated with patient discomfort related to the abnormal eyelash growth that may result in corneal abrasions and ocular complications. Lashes should be clipped every 2 to 4 weeks, and referral to ophthalmologist is needed if irritation and discomfort persist.1
Several preventive measures can be used to manage dermatologic toxicities such as HFSR. A full-body examination with emphasis on hyperkeratotic areas of the palm or sole should be performed prior to treatment initiation, and patients can be encouraged to have a pedicure.16 Patients should be advised to reduce exposure of hands and feet to hot water, reduce traumatic activities within the first 2 to 4 weeks of treatment, avoid constrictive footwear, avoid excessive friction of skin, wear thick cotton gloves or socks, and add padded soles to shoes.15,16,30 Management of HFSR is based on grading and includes a combination of protective measures and use of topical steroids and topical analgesics if pain occurs.
Mr J. is a 52-year-old man who recently received a diagnosis of pancreatic cancer with metastasis to the liver. After discussions related to treatment options, Mr J. opted to try oral erlotinib for palliative treatment of his cancer. Prior to going home and beginning the treatment, Mr J.'s palliative nurse conducted a full body-skin examination to document any existing skin issues that may be exacerbated during treatment. The nurse also gave Mr J. a brochure with instructions on how to protect his skin and nails, and this included the use of emollients for the skin and nail folds, using a sunscreen with SPF of greater than 30, and wearing hats during sun exposures. During a routine evaluation visit 4 weeks after starting erlotinib, Mr J. presented with acnelike rash on his face, upper chest, and back. He stated that his skin was very itchy, and the emollients were not too helpful in stopping the pruritus. Upon examination, the palliative nurse also found fissures and cracks in Mr J.'s nail folds. Mr J. was given instructions to apply liquid glue in his nail folds to keep the fissures from expanding further and to use a bleach soak for his hands to prevent infections. Mr J. was also given a prescription for doxycycline 100 mg daily and topical hydrocortisone 1% cream. At the end of the visit, Mrs J. pulls the palliative care nurse aside and reports that Mr J. was isolating himself and not as socially active as he used to be because he did not want people to see the visible skin rash on his face. Three weeks later, Mr J. was admitted to the hospital for infection secondary to his skin rash. At this time, Mr J.'s cancer has also progressed, and it was decided that treatment would be discontinued. Home hospice care services were initiated, and the hospice nurse noticed that Mr J. was still experiencing residual dermatologic effects from the erlotinib treatment. The hospice nurse continues to assess Mr J.'s dermatologic conditions and make recommendations on self-care strategies during each evaluation visit.
Dermatologic toxicities are the most common adverse effects of targeted therapies in cancer treatment. As more and more targeted agents are used as palliative treatment in cancer, nurses will encounter increasing number of patients who are experiencing these symptoms in palliative care settings. Therefore, vigilance in assessment, prevention, and management of symptomatic dermatologic toxicities is critical to preserve patients' functional status and QOL. Palliative nurses can improve patient care through several methods. First, nurses should become familiar with the recommendations on assessment, prevention, and management of dermatologic toxicities. Although current recommendations are largely anecdotal, they should be used as tools to aid in developing individualized strategies for symptom management based on patient preferences, physical status, and disease condition. In addition, nurses can provide counseling and education for patients on dermatologic symptoms commonly seen with targeted therapies. Finally, nurses can bridge the communication of symptoms between patients and clinicians through advocacy and thorough symptom assessment. Early identification of symptomatic dermatologic toxicities can facilitate treatment in a timely manner and provide referrals to experts in palliative care services for symptom control if warranted.
Treatment-related adverse effects, including those associated with target therapies, continue to be a challenge for healthcare professionals caring for patients with cancer. Nurses must be aware of the common adverse effects associated with novel targeted therapies and methods to assess, prevent, and manage them.
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