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New anticancer therapies have improved patient outcomes but associated dermatologic adverse events (AEs) may cause morbidity and treatment discontinuation. A comprehensive estimation of associations between cancer drugs and skin AEs is lacking. This study utilized the Food and Drug Administartion (FDA)'s Adverse Event Reporting System database (January 2013-September 2022), with 3,399,830 reports involving 3084 drugs and 16,348 AEs. A nearest neighbor matching model was employed to select 10 controls for each case report, utilizing the cosine similarity of demographic and AE severity factors to minimize false positives/negatives. There were 10,698 unique anticancer drugs (n = 212) to skin AE (n = 873) pairs, of which 676 had significant reporting odds ratios (ROR) > 1, comprising 113 drugs and 144 AEs. The minimum ROR was 1.25, and 50% of associations displayed a ROR >10. The most common were rash (51 agents) and dry skin (28 drugs). Methotrexate induced the most distinct AEs (34), then mechlorethamine (33), and vemurafenib (24). Targeted therapies accounted for 49% of pairs, cytotoxic chemotherapies for 35.9%, and immunotherapies for 11%. A total of 113 anticancer drugs were identified as significantly associated with skin AEs, most frequently rash and dry skin. Data are likely under-reported but enable quick postmarketing identification of skin toxicity signals. [ABSTRACT FROM AUTHOR]

Background: MEK inhibitors cause a wide spectrum of mucocutaneous toxicities which can delay or interrupt life-saving therapy. Purpose: To summarize the morphology, incidence, and clinical presentation of mucocutaneous toxicities from MEK inhibitors via a scoping review of the literature. Methods: We conducted a scoping review of the published literature, including clinical trials, retrospective and prospective studies, reviews, and case reports and series. All included literature was analyzed by a panel of pediatric and adult oncodermatologists. Results: Of 1626 initial citations, 227 articles met final inclusion criteria. Our review identified follicular reactions, ocular toxicities, xerosis, eczematous dermatitis, edema, and paronychia as the most common mucocutaneous side effects from MEK inhibitor therapy. Grade 1 and 2 reactions were the most prevalent and were typically managed while continuing treatment; however, grade 3 toxicities requiring dose reductions or treatment interruptions were also reported. Conclusion: Mucocutaneous toxicities to MEK inhibitor therapy are common and most often mild in severity. Early recognition and treatment can mitigate disruptions in oncologic therapy. [ABSTRACT FROM AUTHOR]

Background: Novel oncologic therapies, including epidermal growth factor receptor inhibitors (EGFR-Is) and immune checkpoint inhibitors (ICIs), are associated with a new spectrum of adverse reactions, with prominent cutaneous toxicities. The impact of cutaneous adverse events (cAEs) on patients' quality of life (QoL) represents an unmet clinical need. Objectives: The aims of this study were (1) to assess whether cutaneous toxicities directed therapies are effective in reducing the QoL burden via the submission of 2 patient reported outcome measures (PROMs); (2) to investigate whether class of oncologic therapy, type of cAE and toxicity severity differently impact on patients' QoL. Methods: A prospective observational study was conducted at the Dermatology department of the Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy, from October 2018 to October 2019. Patients aged ≥18 years, under therapy with EGFR-Is or ICIs and experiencing a treatment-related cAE were eligible for the study. Dermatology Life Quality Index (DLQI) and European Organization for Research and Treatment of Cancer Quality of Life Questionnaire – Core 30 version 3.0 (EORTC QLQ-C30) were administered to patients at first clinical visit (T0), at 1-month (T1), and at 3-month (T2) dermatological follow-up. Results: Sixty cAEs of 51 patients have been recorded. A significant difference in the mean score for both DLQI and EORTC QLQ-C30 was found along the 3-months dermatological follow-up (p < 0.0001). A similar QoL improvement was reported for PROMs stratified by class of therapy and toxicity severity (p < 0.0001). No difference was reported for patients with pyogenic granuloma-like lesions and psoriasiform eruption as per DLQI. Class of therapy and toxicity severity did not differently impact on patients' QoL at selected timepoints; we reported a higher EORTC QLQ-C30 score at T2 for patients developing psoriasiform eruption compared to other types of cAEs. Conclusions: Early patients' referral to dermatologists and tailored management could result in better QoL. [ABSTRACT FROM AUTHOR]

Previous studies have shown that combining immune checkpoint inhibitors (ICIs) with talimogene laherparepvec (TVEC) may improve antitumor responses. However, the risk of developing cutaneous immune-related adverse events (cirAEs) in patients treated with ICI and TVEC has not been studied. To evaluate the differences in cirAE development between patients treated with ICI alone and both ICI and TVEC (ICI + TVEC). Patients with cutaneous malignancy receiving ICI with or without TVEC therapy at the Massachusetts General Brigham healthcare system were included. CirAE development, time from ICI initiation to cirAE, cirAE grade, cirAE morphology, and survival were analyzed. Pearson's χ2 test or Fisher's exact test for categorical variables and t test or Kruskal-Wallis test for continuous variables were used. To account for immortal time bias, we performed adjusted time-varying Cox proportional hazards modeling. The rate of cirAE development was 32.3% and 38.7% for ICI only and ICI + TVEC, respectively. After adjusting for covariates, ICI + TVEC was associated with a 2-fold increased risk of cirAE development (hazard ratio: 2.03, P =.006) compared to patients receiving ICI therapy alone. The retrospective nature and limited sample size from a tertiary-level academic center. These findings underscore potential opportunities for dermatologists and oncologists in counseling and monitoring patients. [ABSTRACT FROM AUTHOR]

Ibrutinib is an oral inhibitor of Bruton tyrosine kinase that is approved by the United States Food and Drug Administration for several lymphoproliferative disorders and chronic graft-versus-host disease. To characterize cutaneous eruptions arising from ibrutinib and highlight overlap with epidermal growth factor receptor (EGFR) inhibitor–induced dermatologic adverse events. Single-center retrospective cohort of patients referred to the Skin Toxicities Program for treatment of cutaneous eruptions while taking ibrutinib. Among 19 patients, cutaneous eruptions manifested as facial-predominant papulopustular eruptions, petechiae, or ecchymoses, photosensitivity, panniculitis, xerosis, and clinical staphylococcal overgrowth. Most patients were able to continue ibrutinib therapy with focused treatment of their cutaneous toxicities. This study represents cases at a single tertiary care center and is limited to patients referred for toxicity. With the exception of petechiae, the cutaneous toxicities of ibrutinib overlap with those associated with selective EGFR inhibitors. We observed that these reactions can be successfully managed using approaches for EGFR inhibitor–induced cutaneous adverse events. [ABSTRACT FROM AUTHOR]

Breast-conserving surgery with adjuvant radiation therapy has become the standard of care for women with early stage breast cancer, and as a result, a large number of patients are affected by the cutaneous sequelae of radiation therapy. These dermatologic toxicities may present during treatment or years later and can significantly impact patients’ quality of life. In this review, we discuss the clinical presentation, prevention, and management of radiation-induced cutaneous toxicities in women with breast cancer, including radiation dermatitis, radiation recall, radiation-induced morphea, radiation-induced fibrosis, and cutaneous malignancies in irradiated skin.

Background: Chemotherapy-induced alopecia is psychologically challenging for patients undergoing cancer treatment, and scalp cooling has been shown to prevent or decrease the hair loss.Objective: To evaluate whether access to scalp cooling varies by geographic area in the United States.Methods: Cancer treatment centers offering scalp cooling were identified using data from the Rapunzel Project. Medicare claims data were queried to evaluate the number of chemotherapy infusions occurring in each zip code in the United States. Geographic distribution of chemotherapy infusions and scalp cooling centers was determined using ArcGIS software. The average distance from the geographic center of all 5-digit zip codes in which chemotherapy infusions occur to the nearest scalp cooling center was calculated in miles.Results: There are 366 chemotherapy infusion centers in the United States that offer scalp cooling. Overall, 43.9% of Medicare-billed chemotherapy infusions in the United States occur in zip codes less than 12.5 miles from a scalp cooling center, 24.8% occur between 12.5 and 49.9 miles away, and 31.3% occur more than 50 miles away.Limitations: Our results are only generalizable to patients seen at Medicare-accepting institutions in the United States.Conclusions: Geographic disparities affect which patients can access scalp cooling therapy, and implementation in suburban and rural areas would increase access for patients who wish to preserve their hair while undergoing chemotherapy. [ABSTRACT FROM AUTHOR]

Supportive oncodermatology is an interdisciplinary field, emerging due to increasing dermatological morbidity in patients with cancer and the recognition of the need for greater collaborative and integrated care to improve patient outcomes. These two unique fields (Oncology and Dermatology) may be integrated in various ways, such as through specialised combined clinics, protocols for expedited access, multidisciplinary groups and meetings, and the development of best practices guidelines. This narrative review consolidates the small but growing literature surrounding supportive oncodermatology; discusses the potential benefit and disadvantages, and areas for future research; and suggests a framework for implementation. [ABSTRACT FROM AUTHOR]

Gefitinib (Iressa), is a selective epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), used in the targeted treatment of locally advanced or metastatic non-small cell lung cancer (NSCLC). Skin toxicity is the major adverse effect observed in patients treated with EGFR-targeted TKIs such as gefitinib and erlotinib. To date, a corresponding skin animal model has not been established to address the mechanisms of these effects. Therefore, we analyzed the skin rash phenotype and its pathological features in Brown Norway (BN) rats treated with gefitinib 2.5 mg, 5.0 mg, or 10 mg/100 g/day for 4 weeks. We found that treatment with gefitinib led to weight loss, rash, itching, and hair loss in a dose-dependent manner. We also investigated the skin pathology and found that the animal model showed thickening of the epidermis, loss of moisture, and apoptosis of keratinocytes. Immunohistochemistry, flow cytometry, and analysis of monocytes and leukocytes in the blood revealed increased macrophage infiltration was associated with the cutaneous toxicities induced by gefitinib in the BN rats. Finally, we found that gefitinib-induced cutaneous toxicity is significantly associated with three inflammatory cytokines known to be secreted by activated macrophages, TREM-1, CINC-2, and CINC-3. [ABSTRACT FROM AUTHOR]

Cutaneous toxicities are the most prevalent immune‐related adverse events. Various reactions have been reported. In this review, we summarized the clinicopathologic manifestations, treatment strategies, relevance to tumor outcomes, and rechallenge considerations of cutaneous immune‐related adverse events. [ABSTRACT FROM AUTHOR]

Purpose: Cutaneous toxicities from novel anticancer treatments are an emerging problem in dermato-oncology. However, the prevalence of those toxicities and necessity of skin consultations are currently unknown. The purpose of our study was to perform an epidemiologic analysis of cutaneous toxicities that were referred to our cutaneous toxicity clinic in Athens, Greece.Methods: All patients examined at the oncodermatology department over a 42-month period were included. Gender, age, type of cancer, type of antineoplastic treatment, and type of toxicity were recorded and analyzed.Results: Four hundred fifty-nine patients (182 males, 277 females) with mean age (SD) 60.6 years (13.05) were included in the analysis. Six hundred seventy-two cutaneous toxicities were recorded. Chemotherapy-induced toxicities were the most commonly recorded incidents, with taxanes being the most commonly involved agent. Immune-related adverse events (IRAEs) have steadily increased over the past 3 years. Treatment modifications due to skin toxicities were more common in patients treated with targeted agents and immune checkpoint inhibitors than in those treated with chemotherapy. The toxicities that led to the most treatment modifications were acneiform eruptions and perionychias. The most common IRAEs recorded were psoriasis in 11 patients, followed by pruritus, macular rash, and lichenoid-type eruptions. In addition, 4 interesting cases of IRAEs are discussed.Conclusion: Antineoplastic treatments can lead to a wide range of cutaneous toxicities. Our study underlines the need for a multidisciplinary approach in oncologic patients. The dermatologists' role is crucial in effectively managing those reactions and preventing antineoplastic drug dose adjustments or discontinuation of treatment. [ABSTRACT FROM AUTHOR]

Background: Papulopustular rash is the most common cutaneous adverse effect during targeted tumour therapy particularly with epidermal growth factor receptor inhibitors (EGFRIs). Objective: To evaluate the adverse skin reactions, mainly papulopustular rash, caused by targeted tumour therapy. Materials and methods: We retrospectively analysed the data of patients who were diagnosed papulopustular rash due to targeted chemotherapeutic agents between January 2016 and August 2018. Demographic characteristics of the patients, the type of malignancy, chemotherapeutic agents causing papulopustular rash, clinical features and grade of the rash, treatment modalities used for the rash, other associated cutaneous adverse reactions, and the need for dose-modification or discontinuation of the chemotherapy were recorded. Results: A total of 39 patients (26 males, 13 females) with a median age of 60 (range 32–86) years were included in the study. EGFRIs such as erlotinib, lapatinib, cetuximab, and panitumumab were the main drugs causing papulopustular rash in 2 (5.1%), 3 (7.6%), 18 (46.1%), and 13 (33.3%) patients, respectively. Imatinib, bevacizumab in combination with oxaliplatin, and everolimus in combination with exemestane and goserelin were responsible in three patients. The most commonly affected area was the face (87.1%) followed by the trunk (56.4%), scalp (25.6%), and extremities (23%). The rash was recorded as grade 1, 2, and 3 in 18, 13, and 6 of the patients, respectively. Grade 3 rash was lead to dose interruptions in 5 (12.8%) patients with subsequent reintroduction at a lower dose in 4 (10.2%) of them and discontinuation of the therapy in 1 (2.5%) patient. Pruritus, xerosis, paronychia, increased growth of the eyelashes, mucositis, hand-foot syndrome (HSF), and symmetrical drug-related intertriginous and flexural exanthema (SDRIFE) are other skin toxicities associated with the targeted tumour therapy. Conclusions: With the increasing use of targeted therapies, dermatologists are now confronted with extensive spectrum of skin toxicities. Therefore, it is critical for dermatologists to be aware of these toxicities so as to develop the best approach without discontinuation of cancer therapy. [ABSTRACT FROM AUTHOR]

Abstract Cutaneous toxicities are the commonest side effects in patients with cancer treated using epidermal growth factor receptor inhibitors such as erlotinib. For patients with such toxicities, there is a lack of safe, effective pharmacological agents. Here we established a skin toxicity model and investigated the preventive and therapeutic effect of Diallyl Trisulfide (DATS) in vivo. The mouse skin toxicities model was established through continuous administration of erlotinib for 49 days. Meanwhile, the mice in the experimental group underwent DATS treatment for 49 days. Hematoxylin and eosin (HE) staining and oil red O staining of back and limb skin was performed to determine whether DATS aqueous extract can reverse the skin toxicities caused by erlotinib. Compared with the erlotinib group, the incidence of rash in the DATS group was lower. In addition, in the DATS group, the degree of skin redness and herpes was mild, the body weight was stable, and the activity was favorable. By comparing the HE and oil red O staining results for the mouse skin, the degree of keratin hyperplasia was determined to be lower in the experimental group than in the erlotinib group, and the number of purulent neutrophils decreased. The number of follicles was relatively less. The release of TNF-α, IL-6 and other inflammatory factors was reduced by DATS. Erlotinib hydrochloride can cause severe skin toxicities, and DATS prevents skin toxicities, its mechanism may be related to DATS reduced erlotinib-induced inflammatory injury. Graphical abstract Unlabelled Image Highlights • An animal model of dermal toxicity caused by EGFRI was established. • The skin protection of DATS was confirmed. • It was verified that the skin protection mechanism of DATS is related to the anti-inflammatory effect. [ABSTRACT FROM AUTHOR]

The introduction of targeted therapies in cancer treatment was accompanied with promising results including tumor control and patients survival benefits. However, these drugs just like their predecessors were associated with systemic side effects, including frequent and various cutaneous effects. Targeted therapies such as epidermal growth factor receptor, vascular endothelial growth factor receptor, kit, platelet-derived growth factor receptor, and BCR-ABL inhibitors as well as mammalian target of rapamycin inhibitors can induce cutaneous toxicities of varying severity. There are scarce studies on the actual impact of these toxicities on the patients' lives including the physical, social, and psychological aspects and overall quality of life. Patient's perspective in living with and beyond these toxicities remains largely uncharted but essential in optimizing care provided to those receiving treatment with targeted therapies.

Background: Personalized targeted therapies have become an emerging paradigm in cancer treatment. Although generally more tolerable than other chemotherapeutic agents, one therapy, epidermal growth factor receptor inhibitors (EGFRIs), commonly results in the formation of cutaneous toxicities, which can negatively affect patients' treatment adherence and quality of life. Objectives: The aim of this article is to review nursing management strategies for EGFRI-related cutaneous toxicities. Methods: A systematic literature review was performed, including database searches in PubMed/MEDLINE®, CINAHL®, Cochrane Library, PsycINFO®, and Web of Science. Findings: Nurses are essential to the management of EGFRI-related cutaneous toxicities and are in an ideal position to provide supportive care throughout the course of the EGFRI treatment. The aim of nursing management is to maintain patients' treatment adherence and quality of life by employing a preemptive and proactive approach. Patient education is the most frequently reported management strategy. However, treatment options and management strategies are largely anecdotal and based on individual reports and expert opinions. Although no evidence-based management strategies exist, nurses can rely on existing assessment tools and guidelines to provide patients with symptom management and supportive care. [ABSTRACT FROM AUTHOR]

Cancer patients receiving targeted therapies often develop persistent cutaneous adverse effects, such as papulopustular eruption (rash), xerosis cutis (dry skin), pruritus (itch), and hair and nail changes. These can be dose‐limiting or a cause for therapy discontinuation but also can be wearing on patients, negatively influencing their self‐image and relationships with others. In a Ricoeurian hermeneutic phenomenological study, we aimed to explore the lived experiences of colorectal, pancreatic, and non‐small cell lung cancer patients living with cutaneous toxicities following treatment with targeted agents. Narratives were used to elicit the experiences of 22 cancer patients. Data were analyzed in three steps informed by Ricoeur's interpretation theory: naïve understanding, structural analyses, and comprehensive understanding. Three themes were identified: “Ashamed of what I have become,” “Surrender to cancer,” and “Mourning for the loss of my body,” with nine sub‐themes revealing the multidimensional impact of the adverse effects on the patients' lives. The comprehensive understanding produced in analysis revealed a new contextualized interpretation of being in the world while living with cutaneous toxicities. Treatment‐induced cutaneous toxicities distorted patients' daily living in ways that led to negative manifestations and effects on their self‐image, social engagement, and intimate relationships. Although the dose‐limiting and treatment‐interrupting effects of these toxicities have been reported, this study sheds light on their existential impact, touching on physical, psychological, and social issues. © 2016 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Advancements in cancer therapy with monoclonal immune checkpoint antibody blockade have impacted the practice of all medical specialties. Cutaneous immune-related adverse events (irAEs) are a frequent, unintended, off-target consequence of immune checkpoint inhibitor (ICI) therapy that have ushered in the era of oncodermatopathology. Knowledge of the diverse morphologic types of cutaneous irAEs from ICI therapy allows further classification of cutaneous irAEs according to major histopathologic reaction patterns. Early studies suggest that immune mechanisms of lichenoid dermatitis irAE, psoriasiform dermatitis irAE, and bullous pemphigoid irAE show some similarities and differences from their histopathologic counterparts not associated with ICI therapy., Competing Interests: Disclosure The authors have nothing to disclose., (Copyright © 2021 Elsevier Inc. All rights reserved.)