Sorafenib‐induced premalignant and malignant skin lesions

Williams, Victoria; Cohen, Philip R.

doi:10.1111/j.1365-4632.2010.04822.x

Cited by 33 publications

(31 citation statements)

References 43 publications

(140 reference statements)

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“…In the subgroup of patients with BRAF -mutant tumors, the PFS duration of those who received sorafenib was substantial (20.8 months) but not significantly different from that of those who received placebo (9.4 months), however, this could be explained by the different prognoses of the differing subtypes of DTC. 26 …”

Section: Advanced Thyroid Cancer Managementmentioning

confidence: 99%

“…SCC and keratoacanthomas have also been seen in patients treated with sorafenib, another compound with inhibitory activity against RAF kinases 26,96,97 . Squamous cell tumors in patients treated with the BRAF inhibitors vemurafenib and sorafenib have a distinct mutational profile that indicates a mechanism of therapy-induced tumorigenesis in RAS-primed cells 98,99 .…”

Section: Adverse Effects Of Braf Inhibitors and Suggested Managementmentioning

confidence: 99%

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BRAF Inhibitors: Experience in Thyroid Cancer and General Review of Toxicity

et al. 2014

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The U.S. Food and Drug Administration–approved BRAF inhibitors, vemurafenib and dabrafenib, have demonstrated superior efficacy in patients with BRAF-mutant melanomas but have limited efficacy in BRAF-mutant colorectal cancer. Little is known at this time regarding BRAF inhibitors in thyroid cancer. Initial reports in patients with progressive, radioactive iodine–refractory BRAF-mutant papillary thyroid cancer suggest response rates of approximately 30–40%. In this review, we discuss BRAF inhibitors in the context of thyroid cancer, the toxicities associated with BRAF inhibitors, and the suggested management of those toxicities. The management of vemurafenib and dabrafenib toxicities is applicable across all tumor types and may serve as a practical guide to their use.

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Section: Advanced Thyroid Cancer Managementmentioning

confidence: 99%

Section: Adverse Effects Of Braf Inhibitors and Suggested Managementmentioning

confidence: 99%

BRAF Inhibitors: Experience in Thyroid Cancer and General Review of Toxicity

et al. 2014

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“…Interestingly, many of these lesions are also encountered with the use of the multikinase inhibitor sorafenib, which also inhibits RAF [66,67]. Up to 11% of patients receiving sorafenib develop keratoacanthoma/cuSCC and actinic keratoses, with a median onset of 9 months [68].…”

Section: Cutaneous Toxicitymentioning

confidence: 98%

Skin Toxicity of Targeted Cancer Agents: Mechanisms and Intervention

et al. 2013

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In recent years, targeted agents have rapidly evolved as effective tools in the clinical management of a broad range of malignant diseases. These agents disrupt molecular mechanisms and signaling modules that drive the malignant phenotype in defined subsets of malignancies. Beyond the intended cellular targets crucial to tumor growth and progression, these agents also affect signal transduction in normal cells and tissues. The resulting adverse events and their clinical management continue to change, as newer agents with an ever-increasing target spectrum are developed. We provide a succinct overview of dermatologic toxicities arising from the targeting of receptor tyrosine kinases and downstream effectors. Emergent insights into the pathomechanisms involved and the use of this knowledge base to alleviate cutaneous adverse events are discussed.

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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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Sorafenib‐induced premalignant and malignant skin lesions

Cited by 33 publications

References 43 publications

BRAF Inhibitors: Experience in Thyroid Cancer and General Review of Toxicity

BRAF Inhibitors: Experience in Thyroid Cancer and General Review of Toxicity

Skin Toxicity of Targeted Cancer Agents: Mechanisms and Intervention

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

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