Dermatologic Toxicities Associated With EGFR Inhibitors

Dermatologic toxicities associated with EGFR inhibitors can have a profound impact on patients' health-related quality of life (HRQL) and may interfere with treatment adherence. We interviewed 20 patients and 12 expert clinicians to identify the most bothersome aspects of dermatologic toxicities to better understand the impact on patients' HRQL. Patients and expert clinicians reported that dermatologic toxicities have an impact on patients' physical, functional, emotional, and social well-being. Patients identified the physical discomfort as having the most impact on their HRQL, specifically the sensations of pain, burning, and skin sensitivity. Patients experienced worry, frustration, and depression because of their dermatologic symptoms and reported withdrawing from social activities. Cognitive behavioral strategies such as guided imagery and symptom reframing (eg, rash means treatment is working) may provide patients with valuable skills for the management of this physical discomfort. Cognitive behavioral strategies may also be useful in helping patients manage anxiety and depression associated with any changes in their social function caused by skin rash, as well as distress associated with having a cancer diagnosis.

Health-related quality of life (HRQL) has been defined as the extent to which one's usual or expected physical, emotional, and social well-being are affected by a medical condition or its treatment.[1] Clinical experience suggests that the skin toxicities associated with epidermal growth factor receptor inhibitors (EGFRIs) can have a profound impact on patient's physical, emotional, and social function and may interfere with treatment adherence. Molinari et al examined 13 patients who were treated with cetuximab (Erbitux) for colorectal cancer and found that severity of dermatologic toxicity was associated with impairments in HRQL.[2] The empirical investigation of the aspects of dermatologic toxicities that have the most detrimental impact on patients' HRQL can help to guide interventions to manage these toxicities and maximize patients' HRQL.

EGFR Dermatologic Toxicities and HRQL: Interviews With Patients and Expert Clinicians

Methods

To investigate dermatologic-related symptom burden and HRQL among patients receiving an EGFRI, we conducted qualitative interviews with 20 oncology patients and 12 expert clinicians to capture the most bothersome aspects of dermatologic toxicities and the impact of these symptoms on HRQL. Oncology patients were a mean of 57.0 years of age (range: 34–76 years) and predominantly white (95.0%) and female (75.0%). Participants were diagnosed with lung (55.0%), colorectal (35.0%), or pancreatic (5.0%) cancer, or adenocarcinoma (5.0%). Among the sample 60% received erlotinib (Tarceva) and 40% received cetuximab. Using the National Cancer Institute Common Toxicity Criteria (NCI-CTC) grading system to evaluate skin toxicity, we determined that 15.0% were grade 1, 40.0% were grade 2, and 45.0% were grade 3. Twelve providers with expertise in administering EGFRIs or treating patients with EGFRI-associated skin toxicities were identified. Providers included four oncology nurses, three oncologists, three dermatologists, one dermatology nurse, and one ophthalmologist. Interviews were audiotaped and transcribed. Patients and experts were also given a list of 62 items, many of which were taken from the Skindex questionnaire.[3] Patients rated each item on the basis of its importance to their HRQL. Experts rated items on the basis of their importance to HRQL for patients experiencing dermatologic toxicities. Patients and experts were also asked to circle the 20 items that capture the most important issues for patients with EGFRI-associated dermatologic toxicities.

Results

Table 1 presents the items that patients rated as most important to their HRQL. As indicated in Table 1, the majority of items rated as most important pertained to the physical discomfort associated with dermatologic toxicities. Many items were also identified by experts (eg, my skin hurts; my skin condition affects how well I sleep). Experts identified items that assess the impact on patients' social well-being as very important to HRQL (eg, my skin condition affects my social life; I tend to stay at home because of my skin condition). Although patients' ratings of the items pertaining to social functioning were not as high as expert ratings, social isolation and interference with social functioning were rated by patients as moderately important to HRQL and were frequently identified by patients as important during open-ended interviews.

Quotes were selected from patients' qualitative interviews to illustrate the nature of patients' experience with the physical discomfort associated with EGFRI-induced skin rash. The following quote was taken from a 39-year-old woman undergoing treatment with cetuximab:

"I could not get away from the dryness. The dry, cracking...It felt like I had been sitting in the Arctic in the elements, the rawest elements-the salt, the wind, the abrasion, and the cold. And there was no sense of humidity for like months. It had basically torn away the entire skin and it felt this way...so I would say it was the dryness, the sensitivity and the burning, and the inflammation of the actual pustules."

The next quote was taken from a 49-year-old woman receiving cetuximab:

"It was difficult to sleep because it hurt. And the burn. I had to lay sitting up so the skin would not move because it hurt so much. It was hard to wash. You could not put on any makeup, combing my hair hurt like hell because I have had a lot of hair loss."

During one interview, a patient's husband discussed the psychological impact of the dermatologic toxicities:

"This was the first outward physical appearance of the disease...it's a pretty significant burden to carry around...people look at you and say, 'What is wrong with that woman?' Where before they did not know... before, you could choose who you told about your cancer...and that puts a burden on you, it creates a dynamic that did not exist before...when before you could keep your privacy ."

Several patients discussed similar concerns that their skin rash discloses that they have a serious physical illness, their struggles with how to respond to questions from others, and deciding to whom they should disclose their cancer diagnosis.

Summary of Findings

On the basis of patients and experts ratings of questionnaire items and qualitative interviews, patients and expert clinicians reported a physical, functional, emotional, and social impact of EGFRI-induced skin toxicity. The most commonly reported concerns pertaining to physical well-being were painful, burning, and irritated skin, itching, and increased hair growth. These symptoms interfered with patients' sleep, and their ability to work, their activities of daily living, and their hobbies. Patients experienced worry, frustration, and depression related to their skin symptoms and worried about scars from skin toxicities. Patients reportedly withdrew from social activities because of the impact on their appearance and their concerns about how others would react. Patients also reported that their skin toxicities interfered with their ability to show affection.

Implications for Clinical Management

Effective strategies for the management of the physical discomfort associated with dermatologic toxicities will improve patients' HRQL. Patients may benefit from learning nonpharmacologic techniques for symptom management (eg, guided imagery). Symptom reframing, which involves educating patients that the skin rash is an anticipated and common side effect of treatment, and may indicate response to treatment, will improve patients' abilities to cope with the physical discomfort and the impact on HRQL. Patients should be encouraged to conceptualize their dermatologic toxicities as a reminder that they are actively coping with their cancer by undergoing treatment. Interpreting these toxicities in a constructive manner (ie, treatment is helping), as opposed to a negative interpretation (eg, a reminder that they have cancer), will reduce the adverse impact on patients' HRQL and may reduce the intensity of the physical discomfort patients experience.

Because of concerns about appearance and disclosing their cancer diagnosis to others, patients may withdraw socially in response to their dermatologic toxicities. Social isolation may lead to the onset or exacerbation of a depressive episode. Patients should be educated in the importance of maintaining social activities to minimize the impact of treatment-related side effects on emotional well being. Cognitive-behavioral psychotherapy techniques can be useful in treating anxiety and depression associated with cancer and treatment-related side effects.

Conclusion

Patients reported that physical discomfort had the most impact on HRQL, specifically the sensations of pain and burning, and skin sensitivity. Cognitive-behavioral strategies may provide patients with valuable skills for the management of this physical discomfort and may be useful in assisting patients with managing their anxiety and depression commonly associated with changes in their social function that result from skin rash, as well as the distress associated with having cancer. Research advances and the identification of improved strategies for the management of the physical discomforts associated with EGFRI-induced dermatologic toxicities will ultimately assist in improving HRQL in these patients.

Disclosures:

Lynne I. Wagner has no significant financial interest or other relationship with the manufacturers of any products or providers of any service mentioned in this article. Mario E. Lacouture has received honoraria from OSI Pharmaceuticals, Imclone Systems.

Funding for this supplement was provided by Amgen.

References:

1. Cella DF: Quality of life: Concepts and definition. J Pain Symptom Manage 9:186-192, 1994.

2. Molinari E, De Quatrebarbes J, Andre T, et al: Cetuximab-induced acne. Dermatology 211: 330-333, 2005.

3. Chren MM, Lasek RJ, Quinn LM, et al: Skindex, a quality of life measure for patients with skin disease: Reliability, validity and responsiveness. J Invest Dermatol 107:707-713, 1996.