The histologic spectrum of epithelial neoplasms induced by sorafenib

Kwon, Eun Ji; Kish, L. Stephen; Jaworsky, Christine

doi:10.1016/j.jaad.2008.10.043

Cited by 53 publications

(43 citation statements)

References 41 publications

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“…Recent reports indicated a possible association of epithelial skin cancer growth and sorafenib. In particular actinic keratoses (AKs) and variants of squamous cell carcinoma (SCC) such as keratoacanthoma (KA) or KA-like SCC occurring during sorafenib therapy were described [2,3,4,5,6,7,8] (table 1). …”

Section: Introductionmentioning

confidence: 99%

Does Basal Cell Carcinoma Belong to the Spectrum of Sorafenib-Induced Epithelial Skin Cancers?

Degen

Satzger²,

Voelker³

et al. 2010

Dermatology

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The multikinase inhibitor sorafenib is therapeutically used in various malignancies. Multiple cutaneous side effects are well described but recent reports indicated a possible association of epithelial skin cancer growth during sorafenib therapy. To our knowledge, few cases of actinic keratoses and variants of squamous cell carcinomas associated with sorafenib have been published. We report 2 patients who developed a basal cell carcinoma (BCC) while treated with sorafenib. Interestingly BCC is a tumor which has not been described yet in association with sorafenib therapy. The tumors were excised completely. After termination of sorafenib treatment, no new BCCs or other epithelial skin cancers occurred. There is accumulating evidence in the literature that sorafenib and possibly other targeted agents are associated with an increased occurrence of epithelial skin cancers. These observations are summarized here and complemented by the new observation that al- so BCCs might be associated with sorafenib therapy. The pathogenetic mechanisms are unclear so far but induction of the mitogen-activated protein kinase pathway in wild-type RAF cells by RAF inhibitors might play a role. Patients should be informed of this possible side effect and undergo regular dermatological controls before and during sorafenib therapy.

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Section: Introductionmentioning

confidence: 99%

Does Basal Cell Carcinoma Belong to the Spectrum of Sorafenib-Induced Epithelial Skin Cancers?

Degen

Satzger²,

Voelker³

et al. 2010

Dermatology

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“…Indeed the paradoxical sustained proliferative signal over squamous cells could have increased the proliferation of the eccrine duct epithelium after squamous metaplasia. However, since ESS has not yet been described with other BRAF inhibitors [13,14], the pathogenesis of ESS secondary to vemurafenib may probably not be exclusively linked to the MAPK pathway.…”

Section: Review and Discussionmentioning

confidence: 99%

“…Considering the clinical presentation, a possible alternative or coexisting diagnosis could be milia, which have also been reported secondary to vemurafenib [15,16]. Both follicular infundibular cysts and milia have been documented with the EGFR inhibitors gefitinib and matuzumab, suggesting once again that an upstream role of the MAPK pathway could play a role in these keratinization disorders [14]. …”

Section: Review and Discussionmentioning

confidence: 99%

Vemurafenib-Induced Eccrine Squamous Syringometaplasia

Lescoat

Droitcourt²,

Stock³

et al. 2013

Dermatology

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We report herein a patient treated with vemurafenib for a stage IV melanoma who developed an eruption related to eccrine squamous syringometaplasia (ESS). This entity is a well-described side effect of cytostatic therapies used for malignant neoplasia and is clinically characterized by a symmetric cutaneous eruption composed of papules and vesicles preferentially located on fold and intertriginous areas. It is histologically defined by a squamous metaplasia of eccrine ductal epithelium. ESS represents another skin eruption to be added to the list of cutaneous adverse events associated with vemurafenib, a selective BRAF inhibitor used to treat patients with metastatic melanoma harboring the V600E mutation. The discussion focuses on the pathogenesis of ESS secondary to vemurafenib and on alternative diagnoses.

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“…Furthermore, RAS protooncogen mutation was identified in about 40% of lesions (23). Other drugs that lead to the inhibition of RAF signaling pathway, such as sorafenib or dabrafenib, can also cause squamous cell skin carcinoma in up to 10% of all treated patients (24,25). Therefore it has been suggested that RAF inhibition has a direct role in secondary malignancy development in these patients.…”

Section: Kerathoacantoma and Squamous Cell Skin Carcinomamentioning

confidence: 99%

Skin toxicity of targeted therapy: Vemurafenib, first experiences from Montenegro

Todorović

Martinovic

2015

SANAMED

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Introduction: Data on melanoma incidence and mortality in Montenegro is only partially complete. GLOBOCAN and EUCAN reports estimate melanoma incidence in Montenegro to be between 4.6-7.3 cases/100 000.At least 50% of all metastatic melanoma cell lines carry an activating mutation in the BRAF oncogene. The treatment of advanced melanoma with the selective BRAF inhibitors, such as vemurafenib demonstrated improvement in progression free interval and overall survival when compared to conventional chemotherapy treatment. Up to 95% of patients treated with vemurafenib experience skin toxicity. Material and methods:Five patients with metastatic melanoma have been treated with vemurafenib at the Clinic for Oncology and Radiotherapy Podgorica, Montenegro, during the period 2013-2014. They were treated with standard dose (960 mg twice a day, per os). Data about the occurrence and management of skin side-effects in these patients were retrospectively collected from medical charts. Severity of side-effects was graded using the National Cancer Institute's Common Terminology Criteria for Adverse Events, version 4.0.Results: In 2013, 41 new cases of melanoma were registered in Montenegro, 20 (48.7%) male and 21 (51.3%) female. In 2014, 49 new cases of melanoma were registered, 27 (55.1%) male and 22 (44.9%) female. Two out of five (40%) vemurafenib treated patients experienced photosensitivity, three (60%) had rash eruptions, four (80%) developed alopecia, and two (40%) had dry skin problems. Alteration in nevus color and size occurred in one (20%) patient, and two (40%) patients developed new pigmented lesions.Conclusion: Skin side effects associated with vemurafenib are plentiful, but generally manageable with supportive care measures. In our experience, majority of described side-effects were of grade 1 or 2, and none required dose modifications, or discontinuation of the therapy. Our experience suggests that patients taking BRAF inhibitors should have regular full body skin assessments, both prior to the beginning of the therapy and periodically after its onset. Clinicians should be aware of the skin related toxicities, in order to minimize their impact on treatment efficacy and patients' quality of life.

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The histologic spectrum of epithelial neoplasms induced by sorafenib

Cited by 53 publications

References 41 publications

Does Basal Cell Carcinoma Belong to the Spectrum of Sorafenib-Induced Epithelial Skin Cancers?

Does Basal Cell Carcinoma Belong to the Spectrum of Sorafenib-Induced Epithelial Skin Cancers?

Vemurafenib-Induced Eccrine Squamous Syringometaplasia

Skin toxicity of targeted therapy: Vemurafenib, first experiences from Montenegro

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