Side Effects of vemurafenib: A Synthesis of Findings from 27 Studies

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Original Abstract of the Article

Major Research Findings

Vemurafenib, a BRAF kinase inhibitor, is approved for the treatment of unresectable or metastatic melanoma with BRAF mutations. 21 , 23 , 17 , 2 . It has shown to improve survival in patients with metastatic melanoma. 23 . However, vemurafenib can cause a range of side effects, including skin problems, eye problems, and liver problems. 21 , 26 , 5 .

Reasons for Side Effects

Vemurafenib works by inhibiting the BRAF protein, which is involved in the growth of melanoma cells. However, the BRAF protein is also found in other tissues, such as the skin and eyes, and vemurafenib can also affect these tissues. 21 , 26 . This is why vemurafenib can cause side effects that affect the skin and eyes.

Common Side Effects

Skin

The most common side effect of vemurafenib is skin problems, such as inflammation and rash. 21 , 23 , 13 . Some patients may develop skin cancer, such as squamous cell carcinoma, during vemurafenib treatment. 23 , 10 . Vemurafenib can also induce erythema nodosum-like lesions, which are inflammatory skin lesions. 21 . These lesions may resolve spontaneously or with symptomatic treatment. 21 . Vemurafenib can also cause a transient acantholytic dermatosis, called Grover disease. 17 . It is usually treated with topical emollients and corticosteroids. 17 . However, in severe cases, the dose of vemurafenib may need to be reduced or temporarily discontinued. 21 It is important to monitor the skin for any changes and see a doctor if any new skin problems occur.

Eye

Vemurafenib can cause eye problems, such as uveitis, dry eye, and central serous chorioretinopathy. 26 , 15 . These problems usually respond well to local ophthalmic therapy, such as topical corticosteroids. 26 . However, in some cases, vemurafenib may need to be discontinued. 26 It is important to have regular eye exams while taking vemurafenib.

Liver

Vemurafenib can cause liver problems, such as granulomatous hepatitis. 5 . This can lead to chronic cholestasis. 5 . Regular liver function tests are important to monitor for any problems.

Countermeasures for Side Effects

Skin

Topical corticosteroids or other medications can be used to treat skin inflammation and rash. 21 . In some cases, the dose of vemurafenib may need to be reduced or temporarily discontinued. 21 . It is important to monitor for any changes in the skin and see a doctor if any new skin problems occur.

Eye

Local ophthalmic therapy, such as topical corticosteroids, can be used to treat eye problems. 26 . It is important to have regular eye exams while taking vemurafenib.

Liver

Steroid medications can be used to treat liver problems. 5 . It is important to have regular liver function tests to monitor for any problems.

Comparison between Studies

Common Points of Research

Most studies show that vemurafenib is effective for treating melanoma and improves survival. 23 , 2 . However, it is also reported to cause side effects affecting skin, eyes, and liver. 21 , 26 , 5 .

Differences in Research

The frequency and severity of side effects from vemurafenib vary depending on the study. This could be due to differences in patient demographics, vemurafenib dosage, and duration of treatment, as well as the use of other medications.

Points to Note Regarding Application to Daily Life

Vemurafenib is an effective treatment for melanoma but can cause side effects. If you are considering taking vemurafenib, it's essential to understand the risks and benefits and discuss it with your doctor. Regular medical check-ups during treatment are crucial, and you should immediately report any side effects to your doctor.

Limitations of Current Research

Research on vemurafenib side effects is still ongoing and needs further exploration, especially regarding long-term effects. Effective ways to minimize the risks of side effects are yet to be fully established.

Future Research Directions

Future research should focus on understanding long-term side effects, developing strategies to minimize side effect risks, and discovering biomarkers to predict vemurafenib side effects.

Conclusion

Vemurafenib is a valuable treatment for melanoma, but it can cause side effects. It is crucial to understand the risks and benefits before starting treatment and to be aware of the potential side effects and report any issues to your doctor promptly. Continued research is necessary to improve our understanding of long-term side effects and develop strategies for minimizing their occurrence.

Literature analysis of 27 papers
Positive Content
21
Neutral Content
2
Negative Content
4
Article Type
0
1
0
6
24
1.

Mitogen-activated protein kinase inhibitor-associated retinopathy (MEKAR). A clinical case.

Author: Buenasmañanas-MaesoM, Gutiérrez-MonteroÓ, Reche-SainzJ A, Badillo ArconesE, Monja-AlarcónN, Toledano-FernándezN

Improved cancer prognosis
Neurosensory detachments

This case report describes a 55-year-old woman who developed bilateral neurosensory detachments and blurred vision while on a MEK inhibitor for metastatic melanoma. This retinopathy, known as MEKAR, resolved upon discontinuation of the treatment.

Case ReportsIn the medical field, a report that describes in detail a unique case, an unusual medical condition, or the effect of a treatment. Provides new insights and possibilities for treatment through individual patient cases.

Language : English

2.

Vemurafenib in the Treatment of Erdheim Chester Disease: A Systematic Review.

Author: AzizSyed N, ProanoLucia, CruzClaudio, TenemazaMaria Gabriela, MonterosGustavo, HassenGashaw, BaskarAakash, ArgudoJennifer M, DuenasJonathan B, FabaraStephanie P

ECD treatment
Side effects

Erdheim Chester disease (ECD) is a complex histiocytosis with variable clinical presentation and limited treatment options. This literature review summarizes recent and updated treatments for ECD, highlighting the potential benefits and limitations of different approaches, including BRAFV600 inhibitor therapy.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.

Language : English

3.

Cobimetinib- and vemurafenib-induced granulomatous dermatitis and erythema induratum: A case report.

Author: IafollaMarco Aj, RamsayJennifer, WismerJudy, McWhirterElaine

Attenuated toxicities
Increased survival
Erythema induratum
Granulomatous dermatitis

BRAF and MEK inhibitors together can improve survival for metastatic melanoma patients, but these drugs may cause skin problems like granulomatous dermatitis and erythema induratum.

Case ReportsIn the medical field, a report that describes in detail a unique case, an unusual medical condition, or the effect of a treatment. Provides new insights and possibilities for treatment through individual patient cases.

Language : English

4.

Treatment of hairy cell leukemia.

Author: ChiharaDai, KreitmanRobert J

Hairy cell leukemia treatment
Relapse risk
Treatment resistance

Although purine analogs have been effective for hairy cell leukemia, patients often experience relapses and drug resistance. New treatments have increased the complexity of clinical decision-making.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Meta-AnalysisA statistical technique that integrates the results of multiple studies to draw more general conclusions about a particular issue.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.

Language : English

5.

Vemurafenib-induced granulomatous hepatitis.

Author: SpenglerErin K, KleinerDavid E, FontanaRobert J

Effective oral chemotherapy
Vemurafenib for melanoma
Arthralgia
Fatigue
Hepatotoxicity
Liver abnormalities
Rash

Vemurafenib is a protein kinase inhibitor used to treat patients with BRAF V600E mutated metastatic melanoma. While effective, it can cause side effects like arthralgia, rash, fatigue, and liver abnormalities. This case report details a patient who developed severe vemurafenib-induced granulomatous hepatitis leading to chronic cholestasis, highlighting the potential hepatotoxicity of this drug and other protein kinase inhibitors.

Case ReportsIn the medical field, a report that describes in detail a unique case, an unusual medical condition, or the effect of a treatment. Provides new insights and possibilities for treatment through individual patient cases.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.

Language : English

6.

Drug eruptions associated with tumor therapy: Great imitators.

Author: LudwigCatherine, GohVivien, RajkumarJeffrey, AuJeremiah, TsoukasMaria

Cutaneous adverse effects
Drug eruptions

Chemotherapy drugs can cause various cutaneous reactions, including mucocutaneous reactions, hyperpigmentation, hypersensitivity reactions, hand-foot syndrome, acneiform eruptions, maculopapular eruption, squamous cell carcinomas, photosensitivity, and bullous pemphigoid. Oncologists should be aware of these side effects and counsel patients accordingly.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.

Language : English

7.

Economic Burden of Toxicities Associated with Treating Metastatic Melanoma in the United States.

Author: BilirS Pinar, MaQiufei, ZhaoZhongyun, WehlerElizabeth, MunakataJulie, BarberBeth

High treatment cost

Managing treatment-related adverse events in patients with metastatic melanoma is associated with substantial costs. The most common adverse events were neutropenia, vomiting, anemia, and cutaneous squamous-cell carcinoma.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.

Language : English

8.

Panniculitis Under Successful Targeted Inhibition of the MAPK/ERK Signaling Pathway in a Patient With BRAF V600E-mutated Spindle Cell Oncocytoma of the Pituitary Gland.

Author: SollfrankLukas, LettmaierSebastian, ErdmannMichael, UsluUgur

SCO treatment

Spindle cell oncocytoma (SCO) of the pituitary gland is a rare tumor. Mutational analysis and targeted therapy may be beneficial in treating SCO, as surgical excision and radiation therapy often result in local recurrences.

Case ReportsIn the medical field, a report that describes in detail a unique case, an unusual medical condition, or the effect of a treatment. Provides new insights and possibilities for treatment through individual patient cases.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.

Language : English

9.

Options of Therapeutics and Novel Delivery Systems of Drugs for the Treatment of Melanoma.

Author: WangHongbin, TranTuan T, DuongKatherine T, NguyenTrieu, LeUyen M

Melanoma treatment
Side effects

Melanoma treatment using FDA-approved drugs has limitations due to side effects and patient non-compliance. Novel drug delivery systems, such as nanoparticles and liposomes, have been developed to improve drug delivery, targeting, and bioavailability, potentially reducing toxicity and enhancing treatment effectiveness.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

10.

Nevoid melanoma and eruptive nevi from erlotinib.

Author: SeidmanJason S, EichenfieldDawn Z, OrmeCharisse M

Skin cancer

This study reports a case of a woman with metastatic lung cancer in remission who developed eruptive nevi and a nevoid melanoma after two years of treatment with the EGFR inhibitor erlotinib. The authors speculate that a similar mechanism may occur during treatment with EGFR inhibitors as with BRAF inhibitors. They recommend thorough skin examinations for patients undergoing long-term treatment with erlotinib.

Case ReportsIn the medical field, a report that describes in detail a unique case, an unusual medical condition, or the effect of a treatment. Provides new insights and possibilities for treatment through individual patient cases.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.

Language : English

12.

NRAS Q61R and BRAF G466A mutations in atypical melanocytic lesions newly arising in advanced melanoma patients treated with vemurafenib.

Author: ParekhVishwas, SobankoJoseph, MillerChristopher J, KarakousisGiorgos, XuWei, LetreroRichard, ElenitsasRosalie, XuXiaowei, ElderDavid E, AmaravadiRavi, SchuchterLynn M, NathansonKatherine L, WilsonMelissa A, ChuEmily Y

BRAF inhibition risk
Melanoma risk

Vemurafenib treatment for BRAF mutant melanoma was associated with the development of atypical melanocytic lesions, including NRAS mutations. This highlights the need for careful surveillance of melanocytic lesions in patients on BRAF inhibitor therapy.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.

Language : English

13.

Long-term vemurafenib therapy in advanced melanoma patients: cutaneous toxicity and prognostic implications.

Author: MandelVictor Desmond, MedriMatelda, ManganoniAusilia Maria, PavoniLaura, De RosaFrancesco, RiberoSimone, FocaFlavia, AndreisDaniele, MazzoniLaura, MagiSerena, FarnetaniFrancesca, PallaMarco, UliviPaola, StanganelliIgnazio

Improved melanoma survival
Skin adverse events

Skin adverse events related to vemurafenib were common, with 45 out of 62 patients experiencing at least one event. Long-term survivors tended to experience less frequent and severe skin adverse events.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Observational StudyResearch that observes and collects data on participants' behavior and outcomes in their natural state, without intervention.

Language : English

14.

Lycorine Induces autophagy-associated apoptosis by targeting MEK2 and enhances vemurafenib activity in colorectal cancer.

Author: HuMan, YuZhaomin, MeiPeiyuan, LiJinxiao, LuoDan, ZhangHaiming, ZhouMinfeng, LiangFengxia, ChenRui

CRC treatment

Lycorine, an anti-cancer agent, inhibits MEK2, leading to autophagy-associated apoptosis in colorectal cancer cells. The combination of lycorine and vemurafenib showed better efficacy than monotherapy in treating colorectal cancer both in vitro and in vivo.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

15.

[Ocular toxicity of targeted therapies with MEK inhibitors and BRAF inhibitors in the treatment of metastatic cutaneous melanoma].

Author: FauviauxE, PromelleV, BoucennaV, JanyB, ErreraM H, DelbarreM, BoucennaW

Improved survival rate
Ocular toxicity

This study assessed the incidence, clinical features, and management of ocular complications caused by MEK inhibitors and BRAF inhibitors used for treating metastatic melanoma. While these targeted therapies improve survival rates, they can lead to ocular toxicity. Understanding the potential risks and appropriate management strategies is crucial.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Observational StudyResearch that observes and collects data on participants' behavior and outcomes in their natural state, without intervention.

Language : French

16.

Painful nipple hyperkeratosis secondary to vemurafenib.

Author: CarrEmily S, BrownShannon C, FialaKatherine H

Melanoma treatment
Areola hyperkeratosis
Nipple hyperkeratosis

This case report describes two patients who developed nipple hyperkeratosis as a side effect of vemurafenib treatment for melanoma. The condition was successfully treated with tretinoin cream. This finding highlights the importance of dermatologists being aware of this potential side effect.

Case ReportsIn the medical field, a report that describes in detail a unique case, an unusual medical condition, or the effect of a treatment. Provides new insights and possibilities for treatment through individual patient cases.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.

Language : English

17.

BRAF inhibitor and hairy cell leukemia-related transient acantholytic dermatosis.

Author: SinghAmy Garcia, Tchanque-FossuoCatherine N, ElwoodHillary, DurkinJohn R

GD treatment
Vemurafenib side effects

Grover disease (GD) is an acquired, transient or persistent acantholytic dermatosis. This report describes a 72-year-old man who developed GD after two weeks of treatment with vemurafenib without a MEK inhibitor. GD is increasingly reported as an immune-related adverse event in patients on BRAF inhibitor monotherapy. The patient was successfully treated with topical emollients, a corticosteroid, and temporary discontinuation of vemurafenib.

Case ReportsIn the medical field, a report that describes in detail a unique case, an unusual medical condition, or the effect of a treatment. Provides new insights and possibilities for treatment through individual patient cases.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.

Language : English

18.

Design, synthesis and biological evaluation of novel benzo-&#945;-pyrone containing piperazine derivatives as potential BRAF<sup>V600E</sup> inhibitors.

Author: ChenLong-Wang, WangZe-Feng, ZhuBo, ManRuo-Jun, LiuYan-Dong, ZhangYuan-Heng, WangBao-Zhong, WangZhong-Chang, ZhuHai-Liang

Anticancer effect
Potent BRAF<sup>V600E</sup> inhibitor

This study identified a new and potent BRAF<sup>V600E</sup> inhibitor (3l) which induced cell apoptosis and marked DNA fragmentation, and arrested the cell cycle at the G0/G1 phase in melanoma cells. The biological profile of 3l suggests that this compound may be developed as a potential anticancer agent.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

19.

Discrete cytosolic macromolecular BRAF complexes exhibit distinct activities and composition.

Author: DiedrichBritta, RigboltKristoffer Tg, RöringMichael, HerrRicarda, Kaeser-PebernardStephanie, GretzmeierChristine, MurphyRobert F, BrummerTilman, DengjelJörn

Paradoxical action
Side effects

BRAF, a serine/threonine kinase, plays a crucial role in the RAS/ERK pathway and is frequently mutated in tumors. This study investigates the protein-protein interactions of hyperactive BRAF<sup>V</sup><sup>600E</sup> and wild-type BRAF (BRAF<sup>WT</sup>), revealing that the quaternary structure of BRAF complexes is influenced by its activation status, the conformation of its kinase domain, and clinically relevant inhibitors.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

21.

[BRAF Inhibitor-Induced Erythema Nodosum-Like Lesions].

Author: ShibaKeiko, MoriuchiReine, MoritaYusuke, NakamuraMichio, TakigamiMasayoshi, ShimizuSatoko

Melanoma treatment
Erythema nodosum
Skin lesions

Vemurafenib, a BRAF inhibitor, has been associated with erythema nodosum-like lesions as a side effect. This report describes the first Japanese case of this adverse reaction and discusses the countermeasures.

Case ReportsIn the medical field, a report that describes in detail a unique case, an unusual medical condition, or the effect of a treatment. Provides new insights and possibilities for treatment through individual patient cases.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.

Language : Japanese

23.

Vemurafenib-related cutaneous side effects ameliorated by acitretin.

Author: ChonSusan Y, SambranoBrittany L, GeddesElizabeth R

Melanoma treatment
Survival improvement
Cutaneous neoplasms
Skin cancer development

Vemurafenib, a BRAF kinase inhibitor, is effective in treating metastatic melanoma but can cause cutaneous neoplasms, including squamous cell carcinomas (SCCs), keratoacanthomas (KAs), and hyperkeratotic papules. This article discusses the potential benefits and risks of using systemic retinoids for chemoprophylaxis in individuals at high risk for skin cancers.

Case ReportsIn the medical field, a report that describes in detail a unique case, an unusual medical condition, or the effect of a treatment. Provides new insights and possibilities for treatment through individual patient cases.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.

Language : English

25.

Adefovir dipivoxil sensitizes colon cancer cells to vemurafenib by disrupting the KCTD12-CDK1 interaction.

Author: YangJie, XuWen Wen, HongPan, YeFei, HuangXiao-Hui, HuHui-Fang, ZhangQi-Hua, YanXin, LiBin, HeQing-Yu

Colon cancer treatment
Melanoma treatment

Vemurafenib resistance in colon cancer is linked to CDK1 activation. Adefovir dipivoxil, an FDA-approved drug, disrupts CDK1 activation and sensitizes resistant cells to vemurafenib, offering a new therapeutic strategy for colon cancer.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

27.

Post-Marketing Safety of Vemurafenib: A Real-World Pharmacovigilance Study of the FDA Adverse Event Reporting System.

Author: LiuYanxin, DongChangjiang, HeXucheng, ShuYamin, WuPan, ZouJian

AEs

A safety analysis of vemurafenib using real-world data from the Food and Drug Administration Adverse Event Reporting System (FAERS) identified and characterized potential adverse events associated with this BRAF V600 variation metastatic melanoma treatment.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

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