Cutaneous adverse effects of <scp>BRAF</scp> inhibitors in metastatic malignant melanoma, a prospective study in 20 patients.

Vanneste, L; Wolter, Pascal; Stas, Marguerite; Garmyn, Marjan

doi:10.1111/jdv.12449

Cited by 32 publications

(18 citation statements)

References 19 publications

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“…Among the 131 patients treated with vemurafenib over a 50‐month period in this cohort, 26% developed grade 3–4 severe skin toxicity leading to treatment discontinuation in 44% of cases. Our rate of all‐grade skin toxicity of 89% was consistent with the literature, while the rate of grade 3 rash of 19%, and of treatment discontinuation of 11% were higher than those usually reported . Permanent vemurafenib discontinuation is exceptional in clinical studies: no patient in Phase I and II studies and 1.5% of patients in Phase III studies due to rash, SJS, toxic epidermal necrolysis, cellulitis and flushing .…”

Section: Discussionsupporting

confidence: 89%

Profile of vemurafenib‐induced severe skin toxicities

Peuvrel

Quéreux

Saint‐Jean

et al. 2015

Acad Dermatol Venereol

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In this study, vemurafenib was continued in 56% of patients with grade 3-4 skin toxicity, which was associated with prolonged overall survival when emerging within the first 4 and 8 weeks of treatment. While developing severe skin adverse reactions permanently contraindicates vemurafenib use, other rashes should lead to retreatment attempts with dose reduction. In case of recurrence, dabrafenib seems to be an interesting option. For other skin toxicities, including photosensitivity and cutaneous carcinoma, treatment adjustment is usually not needed.

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Section: Discussionsupporting

confidence: 89%

Profile of vemurafenib‐induced severe skin toxicities

Peuvrel

Quéreux

Saint‐Jean

et al. 2015

Acad Dermatol Venereol

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“…BRAF acts as an upstream signaler and promotor of cellular differentiation and proliferation in the mitogen‐activated protein kinase (MAPK) pathway. Inhibition of the wild‐type BRAF in non‐cancerous cells, such as keratinocytes, can lead to potentiated MAPK signaling (Vanneste et al, ). Potentiated MAPK signaling leads to prevention of apoptosis, excessive cell proliferation, and prolonged cell survival (Cohen, Bedikian, & Kim, ).…”

Section: Discussionmentioning

confidence: 99%

Painful nipple hyperkeratosis secondary to vemurafenib

Carr

Brown

Fiala

2017

Dermatologic Therapy

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Vemurafenib is a selected BRAF kinase inhibitor approved for treating metastatic or unresectable melanoma, which has numerous cutaneous side effects unfortunately, including three previously reported cases of asymptomatic areola and/or nipple hyperkeratosis. We present the first case of painful bilateral nipple hyperkeratosis secondary to vemurafenib in an 84-year-old woman. She was successfully treated with tretinoin 0.05% cream that allowed her to comfortably continue treatment. With increased awareness of this condition, we found a second case of asymptomatic nipple hyperkeratosis secondary to vemurafenib in our clinic. As this medication gains acceptance for treatment of metastatic melanoma, it is imperative that dermatologists are aware of this potentially uncomfortable side effect that can result in decreased compliance and impaired quality of life.

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“…A systematic review of 18 TCT drugs found 17.4% incidence of all-grade pruritus 108 . Alopecia can occur with BRAF (vemurafenib, dabrafenib) 109 and VEGFR inhibitors (sorafenib) 110 , albeit at significantly lower frequency than with conventional chemotherapy.…”

Section: Dermatologic Toxicitiesmentioning

confidence: 99%

Kinase inhibitors and monoclonal antibodies in oncology: clinical implications

2015

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Molecularly targeted cancer therapies, such as small-molecule kinase inhibitors and monoclonal antibodies, constitute a rapidly growing and an important part of the oncology armamentarium. Unlike conventional (cytotoxic) chemotherapeutics, targeted therapies were designed to disrupt cancer cell pathogenesis at specific biological points essential for the development and progression of the tumour. These agents were developed to disrupt specific targets with the aim of minimizing treatment burden compared with conventional chemotherapy. Nevertheless the increasingly common use of targeted therapies has revealed some unanticipated, often clinically significant toxic effects, as well as compromising effective palliative and end-of-life management approaches. Although patients and clinicians welcome improvements in cancer prognosis, these changes can also impact patient quality-of-life. Therefore, as demand for oncology expertise increases, physicians need to apprise themselves of targeted therapies and their clinical implications, including drug-specific side effects, impact on quality of life, and cost issues, especially in relation to end-of-life care. This Review provides a useful summary and guide for professionals treating patients with malignant diseases.

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Cutaneous adverse effects of BRAF inhibitors in metastatic malignant melanoma, a prospective study in 20 patients.

Cited by 32 publications

References 19 publications

Profile of vemurafenib‐induced severe skin toxicities

Profile of vemurafenib‐induced severe skin toxicities

Painful nipple hyperkeratosis secondary to vemurafenib

Kinase inhibitors and monoclonal antibodies in oncology: clinical implications

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