Profile of vemurafenib‐induced severe skin toxicities

Peuvrel, L.; Quéreux, G.; Saint‐Jean, M.; Brocard, Anabelle; Nguyen, Jean–Michel; Khammari, Amir; Knol, Anne-Chantal; Varey, Émilie; Dréno, Brigitte

doi:10.1111/jdv.13443

Cited by 29 publications

(43 citation statements)

References 24 publications

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“…These include anti-hepatitis C virus agents (boceprevir and telaprevir) [42,43,44], targeted therapies for oncological diseases (sorafenib [46], vismodegib [47], and vemurafenib [48]), a new anti-coagulant (rivaroxaban) [49], and a new uric acid-lowering agent (fubuxostat) [50]. Although these agents are not notorious for inducing DRESS syndrome, such reports reflect the fact that with increasing introductions of new drugs, the list of culprit drugs for DRESS syndrome will continue to grow.…”

Section: Clinical Featuresmentioning

confidence: 99%

Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS): An Interplay among Drugs, Viruses, and Immune System

Cho

Yang

Chu

2017

IJMS

213

276

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Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a severe multiorgan hypersensitivity reaction mostly caused by a limited number of eliciting drugs in patients with a genetic predisposition. Patients with DRESS syndrome present with characteristic but variable clinical and pathological features. Reactivation of human herpesviruses (HHV), especially HHV-6, is the hallmark of the disease. Anti-viral immune responses intertwined with drug hypersensitivity make the disease more complicated and protracted. In recent years, emerging studies have outlined the disease more clearly, though several important questions remain unresolved. In this review, we provide an overview of DRESS syndrome, including clinical presentations, histopathological features, pathomechanisms, and treatments.

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Section: Clinical Featuresmentioning

confidence: 99%

Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS): An Interplay among Drugs, Viruses, and Immune System

Cho

Yang

Chu

2017

IJMS

213

276

View full text Add to dashboard Cite

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“…These are successful in some patients, but there are significant adverse events associated with them. 2,3 Additionally, many tumors develop resistance to currently available therapies, which is a common problem with the use of vemurafenib. 4,5 Thus, novel cancer therapeutics are needed to work alone or in combination with existing agents to combat this lethal malignancy.…”

Section: Introductionmentioning

confidence: 99%

Expression profile of SIRT2 in human melanoma and implications for sirtuin-based chemotherapy

et al. 2017

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Melanoma is cancer of melanin-containing melanocyte cells. This neoplasm is one of the most deadly forms of skin cancer, and currently available therapeutic options are insufficient in significantly improve outcomes for many patients. Therefore, novel targets are required to effectively manage this neoplasm. Several sirtuins have previously been found to be upregulated in melanoma, so in this study, the expression profile of SIRT2 was determined. Employing a tissue microarray containing benign nevi, primary melanomas, and lymph node metastases, we have found that the tissue from lymph node metastases appears to have a significant upregulation of SIRT2 relative to primary tumors across the nuclear, cytoplasmic, and whole cell data. Additionally, SIRT2 staining was found to be higher in the nucleus of metastatic melanomas compared to cytoplasmic staining. As SIRT2 is considered to be a predominantly cytoplasmic protein, this is a novel and very interesting finding. This, combined with previous studies that show other sirtuins are increased in melanoma and involved in cellular proliferation and survival, leads to the suggestion that exploring pan-sirtuin inhibitors may be the best target for the next iteration of melanoma chemotherapeutics.

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“…Analysis of the prevalence of all‐grade cSCC associated with heterogeneity in patients with melanoma was performed for eight studies . Testing for interstudy heterogeneity gave significant results [ Q = 85.56; P < 0.01; I 2 = 91.8% (high heterogeneity was I 2 > 50%)].…”

Section: Resultsmentioning

confidence: 99%

Systematic review and meta-analysis of prevalence of dermatological toxicities associated with vemurafenib treatment in patients with melanoma

Chen

Zhou

2018

Clin Exp Dermatol

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Summary Background Vemurafenib has been linked to dermatological adverse events in patients with melanoma, including an increased risk of rash, cutaneous squamous cell carcinoma, photosensitivity reaction and keratoacanthoma. However, there has been no systematic attempt to assess the dermatological toxicity data of vemurafenib associated with melanoma treatment. Aim To evaluate the point prevalence of dermatological toxicities associated with vemurafenib treatment in patients with melanoma. Methods Searches were conducted of the electronic databases PubMed and EMBASE and of conference abstracts published by the American Society of Clinical Oncology. Eligible studies included prospective clinical trials and expanded‐access programmes (i.e. outside a clinical trial) of patients with melanoma assigned to vemurafenib treatment. Outcomes included prevalence of dermatological toxicities treated with vemurafenib. Statistical analyses were performed using the R2.8.1 meta package. Results In total, 11 studies comprising 4197 patients were included in the meta‐analysis. For patients assigned to vemurafenib, the overall prevalence of all‐grade cutaneous squamous cell carcinoma (cSCC) was 18.00% (95% CI 12.00–26.00%), rash 45.00% (95% CI 34.00–57.00%), photosensitivity reaction (PR) 30.00% (95% CI 23.00–38.00%), keratoacanthoma (KA) 10.00% (95% CI 6.00–15.00%) and hand–foot skin reaction (HFSR) 9.00% (95% CI 4.00–20.00%), while the prevalence of high‐grade events was: cSCC 16.00% (95% CI 11.00–23.00%), rash 12.00% (95% CI 3.00–38.00%), PR 4% (95% CI 2.00–8.00%) and KA 6.00% (95% CI 5.00–7.00%). Conclusion The most frequent dermatological toxicities associated with vemurafenib treatment in patients with melanoma were cSCC, rash, PR and KA. These data may be useful for estimation of the efficacy and safety of the drug during clinical treatment and for reducing the prevalence of adverse reactions to vemurafenib treatment in patients with melanoma.

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Profile of vemurafenib‐induced severe skin toxicities

Cited by 29 publications

References 24 publications

Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS): An Interplay among Drugs, Viruses, and Immune System

Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS): An Interplay among Drugs, Viruses, and Immune System

Expression profile of SIRT2 in human melanoma and implications for sirtuin-based chemotherapy

Systematic review and meta-analysis of prevalence of dermatological toxicities associated with vemurafenib treatment in patients with melanoma

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