FIGURE 5 - uploaded by Stanculeanu Dana Lucia
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Upper left: periocular papillomas; upper right: erythema multiforme-like lesions, soft bullae with serous fl uid content, surrounded by and erythemato-edematous ring, on a red-violaceous background (targetoid lesions); lower left and right: small, slightly erythematous papules and nodules, (metastases versus dermatofi bromas)
Source publication
Antineoplastic targeted therapies, such as EGFR inhibitors, tyrosine kinase inhibitors and BRAF inhibitors, frequently lead to systemic and cutaneous side effects, significantly affecting patient's quality of life. Patients with new targeted therapies have an increased risk of developing skin reactions. The new molecular target therapies developed...
Contexts in source publication
Context 1
... reactions due to BRAF inhibitors are papular eruptions, photosensitivity, xerosis, pruritus, paronychia, alopecia and hair changes, hyperkeratotic lesions. Vemurafenib and Dabrafenib patients can develop warts, seborrheic keratoses, hypertrophic actinic keratoses, eczemas, hand-foot syndrome, papillomas, keratoachantomas and squamous cell carcinomas, most of which are related to Vemurafenib. Dabrafenib is an appro- priate therapeutic option in patients that do not tolerate Vemurafenib ( Figure 5). Trametinib is a MAPK inhibitor approved for inoperable melano- mas with V600E BRAF or V600K mutations. Cutaneous adverse reactions are less frequent and comprise acneiform eruptions, pruritus and xerosis. Squamous cell carcinoma secondary to Trametinib administration is uncommon com- paring to BRAF inhibitors. Dabrafenib plus Trametinib and Vemurafenib plus Cobimetinib associations have similar efficacy, but with a lower incidence of skin toxicities or either malignant or hyperproliferative disorders. This is due to the paradoxical activation of the MAPK pathway. Addition of a MEK inhibitor leads to the inhibition of RAS signaling in MAPK pathway, which prevents cellular proliferation. Fever is the most important adverse reaction of the Dabrafenib plus Trametinib combination and may lead to dose reduction or treatment discontinuation ...
Context 2
... and Dabrafenib patients can develop warts, seborrheic keratoses, hypertrophic actinic keratoses, eczemas, hand-foot syndrome, papillomas, keratoachantomas and squamous cell carcinomas, most of which are related to Vemurafenib. Dabrafenib is an appro- priate therapeutic option in patients that do not tolerate Vemurafenib ( Figure 5). Trametinib is a MAPK inhibitor approved for inoperable melano- mas with V600E BRAF or V600K mutations. ...
Citations
... CCK-8, Cell Counting Kit-8; NHEK, normal human epidermal keratinocyte. nonsteroidal anti-inflammatory drugs (eg, celecoxib); and the avoidance of mechanical stimuli, including hot water, detergents, and tight shoes and socks (Autier et al, 2008;Cabanillas et al, 2019;Lacouture et al, 2008;McLellan et al, 2015;Stanculeanu et al, 2017). However, the pathological mechanisms of HFSR remain unclear, and there is currently no treatment other than palliative therapy. ...
Hand–foot skin reaction is the most common adverse event of multikinase inhibitors, such as sorafenib. Although hand–foot skin reaction is not life threatening, severe cases impair quality of life because of pain and reduced activities of daily living. However, the pathological mechanisms of hand–foot skin reaction have not yet been elucidated in detail, and there is currently no effective treatment. We aimed to identify keratinocyte cytoprotectants against sorafenib toxicity. The screening of cytoprotectants against sorafenib toxicity was performed using cultured normal human epidermal keratinocytes or a reconstructed human epidermis model and off-patent approved drugs in the Prestwick Chemical library. Among 1273 drugs in the chemical library, 8 dose-dependently increased cell viability by >200% in the presence of sorafenib. In the presence of sorafenib, the number of proliferating cell nuclear antigen–positive cells was significantly higher in clofazimine-, cyclosporin A–, and itraconazole-treated reconstructed human epidermis models than in sorafenib-treated models, and candidate drugs suppressed sorafenib-induced apoptosis in normal human epidermal keratinocytes. In addition, clofazimine, itraconazole, and pyrvinium pamoate significantly recovered the phosphorylation of extracellular signal–regulated kinase 1/2 in the presence of sorafenib. Collectively, hit drugs promoted cell viability and normalized keratinocyte proliferation in the presence of sorafenib. These candidate drugs have potential as treatments for multikinase inhibitor–induced hand–foot skin reaction.
... Paronychia and other nail changes, mucositis as well as hair changes are also common. [7][8][9][10] Anticipation of such dermatological adverse effects of newer targeted drugs, obtaining familiarity with their timely management in consultation with dermatologists, proper counseling and reassurance of the patients and family members, can go a long way in alleviating the apprehensions of the treating physicians (oncologist), the patients and their family members. This will also rationalize the decision regarding continuation and discontinuation of the therapy. ...
... Reporting of similarly occurring common malignancies with slight variations have been reported in various studies across the literature. 1,4,8,10 24 (21.43%) of patients started on targeted chemotherapeutic agents during the study period developed various dermatological adverse effects related to skin, hair, nails and mucosae. Similar frequency of dermatological side effect patterns was also found in some previous studies. ...
... 27 Targeted therapies are frequently associated with dermatological and ocular ADRs. 28 A case of pneumothorax occurred shortly after nivolumab infusion and was therefore likely to be due to lymphangioleiomyomatosis. 33 Recurrent pleural effusions in patients with lung cancer treated with nivolumab were also described. 34 This work did not receive any specific funding. ...
We describe the safety profiles of all drug classes used for the treatment of advanced melanoma from the US Food and Drug Administration Adverse Event Reporting System over 2008–2018. Adverse reactions reported in 25 900 pharmacovigilance cases are described for chemotherapies, immunomodulators, targeted therapies and immunotherapies. There was a sharp increase in the number of cases over time, with peaks associated with the launch of new treatments. The adverse reactions diversified over time; notably, skin (alopecias, dermatitis) and retinal disorders were frequently associated with targeted therapies and endocrine disorders (hypothalamus, thyroid and adrenal dysfunctions) with immunotherapies. Less well‐known reactions were also detected, such as neuropsychiatric disorders with targeted therapies and gastrointestinal ulcers, pneumothorax and pleural effusions with immunotherapies. The findings highlight the need for various health professionals (including medical specialists or trained nurses) to enhance management of complications.
... hypertrichosis, trichomegaly or alopecia. The side effects observed in our patients was consistent with previous publications.7,8 Chanprapaph et al. reported xerosis and papulopustular eruption as the two most prevalent side effects observed in their retrospective series of 99 patients on treatment with erlotinib and gefitinib, followed by maculopapular rash, mucositis, paronychia, and trichomegaly.9 ...
Introduction
Novel anti-cancer drugs such as targeted cancer therapies and immune check-point inhibitors (ICIs) have adverse events, especially concerning the skin. The aim of this study is to report an overview of the commonly consulted dermatological side effects of ICIs and targeted cancer therapies in clinical practice, along with their management.
Methods
In this single-center study, we evaluated consecutive oncological patients who were referred from the oncology outpatient clinic to the dermatology outpatient clinic due to skin side effects of ICIs and targeted therapies. All patients were examined and treated at the same day of referral by experienced dermatologists. Patient characteristics, clinical findings, diagnostic workups and treatments were retrieved from outpatient records.
Results
Sixty three patients were enrolled. Most common diagnoses were lung carcinoma, melanoma and colon carcinoma. Fifty patients (79%) were using targeted therapies while 13 (21%) were using ICIs. Xerosis was the most common side effect (44%), followed by acneiform rash, paronychia, eczema and pruritus. Majority of the side effects were grade 2 and 3. Psoriasis was a common side effect of ICIs. One patient had a newly developed dysplastic nevus on vemurafenib treatment. Oncological treatment was not withheld in any of the patients.
Conclusions
This study revealed the most commonly consulted skin side effects of novel anti-cancer drugs and their management in daily practice. We underlie the importance of collaborative work of oncology and dermatology professionals as early management of cutaneous side effects of targeted therapies and ICIs improves patient outcomes.
... Providers should be aware that patients who experience such changes in The present study demonstrated that worse EGFRIassociated health-related QoL was associated with more symptom distress, a more negative body image, and receipt of a higher cumulative dose of target therapy. These findings are consistent with those of prior studies which indicated that more dermatological adverse events [13,36,37], higher regimen dose [38,39], and distress over body image [40,41] may limit ADLs and diminish QoL. Symptom care should involve sun protection, skin care, and concern over appearance. ...
Purpose
The purposes of this study were to assess the levels of symptom distress, body image, and epidermal growth factor receptor inhibitors (EGFRI)-associated health-related quality of life (QoL); identify the factors related to EGFRI-associated health-related QoL; and examine the differences in EGFRI-associated health-related QoL by grade of skin toxicity in mCRC patients receiving target therapy.
Methods
This cross-sectional study examined mCRC patients who received cetuximab-based target therapy from the oncology and CRC inpatient and outpatient departments of a medical center in northern Taiwan. Structured questionnaires were used to measure patients’ symptom distress, body image, and EGFRI-associated health-related QoL.
Results
Of the 111 mCRC patients studied, 79.2% reported acneiform eruption and 52.2% reported paronychia. The most common symptoms were dry skin and itching. Poor EGFRI-associated health-related QoL was associated with more symptom distress, more negative body image, a higher cumulative dose of target therapy, and being married; these factors explained 66.6% of the variance in EGFRI-associated health-related QoL.
Conclusion
Patient-specific skin care and emotional support are needed to relieve distressful dermatological symptoms and emotional distress during and post-treatment for mCRC.
... Another organ that can be affected by TKIs is the skin, as muco-cutaneous adverse reactions such as dryness, rash, hyperkeratosis, hand-foot syndrome, alopecia and mucositis occur frequently [150]. Hand-foot syndrome can manifest as hyperkeratosis, skin ulceration, or vesicles and present with pain, tingling, or paresthesia in affected skin areas which, if severe enough, may lead to interruption discontinuation of treatment [151,152]. The management of mucocutaneous side effects relies on preventive measures such as good skin hydration, urea creams, symptomatic treatment such as targeting neuropathic pain with gabapentin, dose reduction, or discontinuation of treatment with TKI [145,150,151]. ...
... Hand-foot syndrome can manifest as hyperkeratosis, skin ulceration, or vesicles and present with pain, tingling, or paresthesia in affected skin areas which, if severe enough, may lead to interruption discontinuation of treatment [151,152]. The management of mucocutaneous side effects relies on preventive measures such as good skin hydration, urea creams, symptomatic treatment such as targeting neuropathic pain with gabapentin, dose reduction, or discontinuation of treatment with TKI [145,150,151]. ...
The knowledge on thyroid cancer biology has grown over the past decade. Thus, diagnostic and therapeutic strategies to manage thyroid cancer are rapidly evolving. With new insights into tumor biology and cancer genetics, several novel therapies have been approved for the treatment of thyroid cancer. Tyrosine kinase inhibitors (TKIs), such as lenvatinib and sorafenib, have been successfully utilized for the treatment of radioactive iodine (RAI)-refractory metastatic differentiated thyroid cancer (DTC). In addition, pretreatment with mitogen-activated protein kinase (MAPK) inhibitors (trametinib and selumetinib) has been shown to restore RAI avidity in previously RAI-refractory DTCs. Local therapies, such as external beam radiation and radiofrequency/ethanol ablation, have also been employed for treatment of DTC. Vandetanib and cabozantinib are the two TKIs currently approved by the Food and Drug Administration (FDA) for the treatment of medullary thyroid cancer (MTC). Other novel therapies, such as peptide receptor radionuclide therapy and carcinoembryonic antigen (CEA) vaccine, have also been utilized in treating MTC. Ongoing trials on selective rearranged-during-transfection (RET) protooncogene inhibitors, such as LOXO-292 and BLU-667, have demonstrated promising results in the treatment of metastatic MTC resistant to non-selective TKIs. The FDA-approved BRAF/MEK inhibitor combination of dabrafenib and trametinib has revolutionized treatment of BRAFV600E mutation positive anaplastic thyroid cancer. Several other emerging classes of medications, such as gene fusion inhibitors and immune checkpoint inhibitors, are being actively investigated in several clinical trials. In this review, we describe the molecular landscape of thyroid cancer and novel targeted therapies and treatment combinations available for the treatment of metastatic thyroid cancer.
... In pivotal sorafenib trials, HFSR of any grade was reported in 21% and 45% of patients in predominantly Western and Asian populations, respectively [12,13]. HFSR usually presents with a range of symptoms from burning, tingling, and skin erythema to pain, edema, and ulcerations in the extremities; HFSR can interfere with simple daily activities, such as walking or gripping objects [14,15]. Based on current study data, skin sTRAEs may be the first AEs that patients experience following initiation of nivolumab treatment, often developing within the first month. ...
Background
CheckMate 040 assessed the efficacy and safety of nivolumab in patients with advanced hepatocellular carcinoma (HCC). Understanding the safety profile of nivolumab is needed to support the management of treatment-related adverse events (TRAEs). This analysis assessed the safety of nivolumab monotherapy in the phase I/II, open-label CheckMate 040 study.
Materials and Methods
Select TRAEs (sTRAEs; TRAEs with potential immunologic etiology requiring more frequent monitoring) occurring between first dose and 30 days after last dose were analyzed in patients in the dose-escalation and -expansion phases. Time to onset (TTO), time to resolution (TTR), and recurrence of sTRAEs were assessed, and the outcome of treatment with immune-modulating medication (IMM) was evaluated.
Results
The analysis included 262 patients. The most common sTRAE was skin (35.5%), followed by gastrointestinal (14.5%) and hepatic (14.1%) events; the majority were grade 1/2, with 10.7% of patients experiencing grade 3/4 events. One patient had grade 5 pneumonitis. Median (range) TTO ranged from 3.6 (0.1–59.9) weeks for skin sTRAEs to 47.6 (47.1–48.0) weeks for renal sTRAEs. Overall, 68% of sTRAEs resolved, with median (range) TTR ranging from 3.7 (0.1–123.3+) weeks for gastrointestinal sTRAEs to 28.4 (0.1–79.1) weeks for endocrine sTRAEs. Most gastrointestinal and all hepatic events resolved with treatment in accordance with established toxicity management algorithms. In 57 patients (40%), sTRAEs were managed with IMM. Reoccurrence of sTRAEs was uncommon following rechallenge with nivolumab.
Conclusion
Nivolumab demonstrated a manageable safety profile in this analysis of patients with advanced HCC. A majority of sTRAEs resolved with treatment.
... Dermatologic toxicities observed for epidermal growth factor receptor inhibitors (cetuximab and panitumumab) and B-cell lymphocyte depletion from anti-CD20 antibodies (rituximab). [107][108][109][110][111][112] ...
Skin and subcutaneous diseases affect millions of people worldwide, causing significant morbidity. Biologics are becoming increasingly useful for the treatment of many skin diseases, particularly as alternatives for patients who have failed to tolerate or respond to conventional systemic therapies. Biological therapies provide a targeted approach to treatment through interaction with specific components of the underlying immune and inflammatory disease processes. Advances in the understanding of disease pathophysiology for inflammatory skin diseases and in drug development have ushered in biologic therapies in dermatology. Biologic therapies are molecules that target specific proteins implicated in immune-mediated disease. This review article highlights the increasing evidence base for biologics in dermatology for off-label use.
... These three functions we obtained through enrichment analysis were scored in the top three, and other biological processes such as FCER1 related signals and B cell receptor signals may also participate in this mechanism, but they have not been shown the highest relevance. Skin toxicities induced by EGFRI are considered to follow four stages [25,26]: 1) skin irritation and increased skin sensitivity; 2) inflammatory cytokine secretion and local infiltration; 3) T-lymphocyterich papules and pustules; and 4) scleroderma. Inflammation and innate immune response play a key role in the skin toxicity process with the Fig. 7. XZF inhibits skin inflammation in skin toxicities model induced by EGFRI. ...
Skin toxicities induced by epidermal growth factor receptor inhibitors such as Erlotinib plagues clinical challenges. Chinese formulas have a unique advantage in reducing side effects. Here, we aim to investigate the skin protecting function of XiaoZhenFang (XZF), a clinical adjuvant prescription made up of Lonicerae Japonicae Flos, Lithospermum Erythrorhizon, Smilacis Glabrae Rhizoma, Forsythiae Fructus, Spirodelae Herba, Cortex Moutan and Prunellae Spica. Our data showed that XZF aqueous extract effectively reduced skin toxicities induced by Erlotinib in vivo using established mice model. Next, we used a systems pharmacology approach to investigate the pharmacological mechanism of XZF with the goal of understanding its effects at the system, organ, and molecular levels. 44 candidate compounds and 103 potential targets were identified by network pharmacology. Inflammation, cell stress and the EGFR-related signal pathways, which may participate in the skin protection afforded by XZF, were analyzed by gene enrichment. Importantly, our in vivo experimental results largely validated XZF's mechanism of action, as predicted by the system pharmacology analysis. Our study uncovered the effect and mechanism of XZF in attenuating skin toxicities induced by EGFRI, providing a basis for the development of in-hospital preparations and new drugs for the prevention of skin toxicities.
... 113,114 PRIDE syndrome comprises the most frequent reactions associated with anti-EGFR reactions (papules, pustules, paronychia, hair growth disorders, pruritus, and skin and mucosal xerosis). 114 In a recent meta-analysis involving 38 studies, any grade skin toxicities were identical in cetuximab and panitumumab (83.6% versus 84.4%; p = 0.99). However, cetuximab was associated with fewer G3-4 skin toxicities (15.7 versus 23.2%; OR = 0.62, 95%CI 0.53-0.62; ...
... Secondary infection may result in sudden worsening of cutaneous rashes and an alteration in clinical status. 114 Hence, preventive measures are needed, such as adequate hydration of dry areas, decrease in sun exposure, avoiding prolonged skin contact with water, irritants, and solvents. Topical agents can reduce reaction severity. ...
Renal transplantation has become the sole most preferred therapy modality for end-stage renal disease patients. The growing tendency for renal transplants, and prolonged survival of renal recipients, have resulted in a certain number of post-transplant colorectal cancer patients. Antitumor pharmacotherapy in these patients is a dilemma. Substantial impediments such as carcinogenesis of immunosuppressive drugs (ISDs), drug interaction between ISDs and anticancer drugs, and toxicity of anticancer drugs exist. However, experience of antitumor pharmacotherapy in these patients is limited, and the potential risks and benefits have not been reviewed systematically. This review evaluates the potential impediments, summarizes current experience, and provides potential antitumor strategies, including adjuvant, palliative, and subsequent regimens. Moreover, special pharmaceutical care, such as ISDs therapeutic drug monitoring, metabolic enzymes genotype, and drug interaction, are also highlighted.
