Side Effects of trametinib: A Synthesis of Findings from 24 Studies

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Original Abstract of the Article

Main Research Findings

Trametinib is a MEK inhibitor used to treat melanoma with BRAF mutations. 7 This drug is approved as a single agent and in combination with dabrafenib. 15 This medicine has been shown to significantly improve progression-free survival and overall survival compared to chemotherapy. 15 However, trametinib can cause side effects, some of which can be serious.

Reasons for Side Effects

Trametinib works by inhibiting the MEK pathway, a pathway that controls cell growth and proliferation. This pathway plays an important role in the growth and proliferation of cancer cells, such as melanoma. Therefore, while trametinib inhibits the growth and proliferation of cancer cells, it can also affect normal cells.

Common Side Effects

Skin Side Effects

The most common side effects of trametinib are skin-related, such as rash, dry skin, itching, and eczema. 15 , 17 These side effects are usually mild to moderate and can be improved with treatment such as steroid cream.

Gastrointestinal Side Effects

Gastrointestinal side effects include diarrhea, nausea, vomiting, and abdominal pain. 15 , 21 , 20 These side effects are usually mild to moderate and can be improved with diet and medication.

Eye Side Effects

Eye side effects include vision loss, conjunctivitis, eye pain, and dry eyes. 2 , 20 These side effects can be serious, so it is important to see an ophthalmologist if you experience them.

Muscle Side Effects

Muscle side effects include muscle pain, muscle fatigue, and muscle cramps. 16 , 20 These side effects can be serious, so it is important to see a doctor if you experience them.

Other

Other possible side effects of trametinib include fatigue, fever, weight gain, high blood pressure, and liver dysfunction. 15 , 9 , 23 , 6 , 4 , 24 These side effects can be serious, so it is important to see a doctor if you experience them.

Side Effect Management

Skin Side Effects

Skin side effects can be improved with treatment such as steroid cream. 15 , 17

Gastrointestinal Side Effects

Gastrointestinal side effects can be improved with diet and medication. 15 , 21 , 20

Eye Side Effects

Eye side effects can be serious, so it is important to see an ophthalmologist if you experience them. 2 , 20

Muscle Side Effects

Muscle side effects can be serious, so it is important to see a doctor if you experience them. 16 , 20

Other

Other side effects require medical attention. 15 , 9 , 23 , 6 , 4 , 24

Comparison Between Studies

Similarities in Studies

These studies showed that trametinib is effective in treating melanoma with BRAF mutations. 7 , 21 , 16 , 15 These studies also showed that trametinib can cause side effects.

Differences in Studies

These studies differed in the frequency and severity of side effects that could be caused by trametinib. 17 , 16 , 4 , 20 For example, one study showed that trametinib is often associated with eye side effects. 2 However, another study showed that trametinib rarely causes eye side effects. 21 These differences in research findings may be due to differences in research design and patient populations.

Considerations for Application in Real Life

Trametinib can cause side effects, so it is important to take it under the guidance of a doctor. 19 Before taking trametinib, it is important to tell your doctor about your health status in detail. In particular, if you have allergies, are pregnant, or are breastfeeding, talk to your doctor. Also, if you experience side effects while taking trametinib, consult your doctor immediately.

Limitations of Current Research

There is not enough research on the side effects of trametinib. 10 , 18 In particular, research on long-term side effects is lacking.

Future Research Directions

More research is needed to better understand the side effects of trametinib. 10 , 18 New treatments need to be developed to reduce the side effects of trametinib.

Conclusion

Trametinib is an effective drug for treating melanoma with BRAF mutations, but it can cause side effects. 7 It is important to understand the side effects and take trametinib under the guidance of a doctor.

Literature analysis of 24 papers
Positive Content
20
Neutral Content
2
Negative Content
2
Article Type
1
0
0
4
18
1.

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

2.

Choroidal thickening with serous retinal detachment in BRAF/MEK inhibitor-induced uveitis: A case report.

Author: KiralyPeter, GroznikAlenka Lavrič, ValentinčičNataša Vidovič, MekjavićPolona Jaki, UrbančičMojca, OcvirkJanja, MestiTanja

Melanoma treatment
Panuveitis
Retinal detachment
Thickened choroid

A case report describes a patient with metastatic cutaneous melanoma who experienced bilateral panuveitis, a rare and vision-threatening ocular adverse effect associated with dabrafenib and trametinib targeted therapy.

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

3.

Hair and nail adverse events during treatment with targeted therapies for metastatic melanoma.

Author: DikaEmi, PatriziAnnalisa, RiberoSimone, FantiPier Alessandro, StaraceMichela, MelottiBarbara, SperandiFrancesca, PiracciniBianca Maria

Melanoma treatment
Hair loss
Nail changes

This study examines the hair and nail side effects of targeted therapies for melanoma, specifically BRAF and MEK inhibitors, finding that hair changes and onycholysis are common side effects.

Clinical Trial, Phase IIA Phase II trial is a trial that further evaluates the efficacy and safety of a new drug or treatment, whose safety has been confirmed to some extent in a Phase I trial, in a small number of patients.
Clinical Trial, Phase IIIA Phase III trial is a trial that further rigorously verifies the efficacy and safety of a new drug or treatment, whose efficacy and safety have been confirmed in a Phase II trial, in a large number of patients, and evaluates whether it is superior to existing treatments.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.

Language : English

5.

Successful use of trametinib and dasatinib combined with chemotherapy in the treatment of Ph-positive B-cell acute lymphoblastic leukemia: A case report.

Author: WangJing, ShenShu-Hong, HuBin-Fei, WangGuan-Ling

ALL treatment
Trametinib and dasatinib side effects

This report describes the successful use of trametinib and dasatinib in a pediatric patient with Ph+ ALL and recurrent pancreatitis.

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

6.

A Rare Case of Pituitary Melanoma Metastasis: A Dramatic and Prolonged Response to Dabrafenib-Trametinib Therapy.

Author: MormandoMarilda, PulianiGiulia, BarnabeiAgnese, LaurettaRosa, BianchiniMarta, ChiefariAlfonsina, RussilloMichelangelo, CognettiFrancesco, RomanoLuisa, AppetecchiaMarialuisa

Melanoma treatment

A patient with melanoma metastasis to the pituitary gland was successfully treated with a combination of dabrafenib and trametinib after incomplete surgical removal.

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

7.

BRAF and MEK inhibition in melanoma.

Author: DossettLesly A, KudchadkarRagini R, ZagerJonathan S

Melanoma response
Survival improvement

This review discusses the use of BRAF and MEK inhibitors in combination therapy for BRAF-mutant metastatic melanoma, highlighting its potential to improve efficacy and reduce side effects.

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

8.

Erythema nodosum-like lesions during BRAF inhibitor therapy: Report on 16 new cases and review of the literature.

Author: MössnerR, ZimmerL, BerkingC, HoellerC, LoquaiC, RichtigE, KählerK C, HasselJ C, GutzmerR, UgurelS

Skin lesions often resolve
Erythema nodosum-like lesions
Treatment discontinuation

This study investigated cases of erythema nodosum-like inflammatory skin lesions associated with BRAF inhibitor therapy for BRAF-mutated melanoma. 16 patients developed these lesions, 14 receiving vemurafenib and 2 receiving dabrafenib plus trametinib. Histopathology revealed panniculitis or vasculitis in 5 cases. Symptomatic management was sufficient in most cases, but 3 patients discontinued treatment due to severe symptoms.

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

10.

Intermittent BRAF Inhibition Can Achieve Prolonged Disease Control in BRAF Mutant Melanoma.

Author: JainTania, BryceAlan

Improved survival
Prolonged response
Toxicity

Intermittent BRAF inhibitor therapy with dabrafenib and trametinib has demonstrated prolonged response in a metastatic melanoma patient, achieving disease control for 48 months.

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

11.

BRAF V600E-mutated metastatic pediatric Wilms tumor with complete response to targeted RAF/MEK inhibition.

Author: ObasajuPatience, ShahabShubin, DunnEmily, RheeDaniel S, JiangLiQun, DomeJeffrey S, FriedmanAlan D, ArganiPedram, PratilasChristine A

BRAF V600E mutation
WT treatment
None mentioned

Wilms tumor (WT) is the most common renal malignancy in childhood. This case report describes a child with recurrent, pulmonary metastatic, favorable histology WT harboring a BRAF V600E mutation. The patient initially responded to standard chemotherapy but relapsed. Following confirmation of the BRAF V600E mutation, the patient received combination therapy with dabrafenib and trametinib, leading to a complete radiographic response. This is the first reported case of effective BRAF/MEK targeted therapy in a pediatric Wilms tumor patient.

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.

Papillary Thyroid Cancer Differentiating Into Anaplastic Carcinoma With Near-Complete Response to Targeted Dabrafenib/Trametinib Combination Therapy.

Author: KulkarniPruthali, HallJames, WangLiping, HendersonSherronda

Anaplastic thyroid cancer treatment
Fever
Uveitis

This case report describes a patient with anaplastic thyroid carcinoma with a BRAF V600E mutation who had a dramatic response to dabrafenib/trametinib therapy.

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

13.

Failure of adjuvant treatment for malignant melanoma - what next?

Author: ŽiaranMiroslav, DvořákPetr, HoffmannPetr, KopeckýJindřich

Adjuvant therapy for melanoma

This case study describes a possible treatment approach for patients with malignant melanoma who have experienced relapse or generalization after adjuvant therapy.

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

15.

Trametinib: A Targeted Therapy in Metastatic Melanoma.

Author: HoffnerBrianna, BenchichKatherine

Overall survival advantage
Progression-free survival
Trametinib efficacy
Diarrhea
Fatigue
Nausea
Peripheral edema
Pyrexia
Rash

Trametinib, a MEK inhibitor, is an effective treatment option for BRAF V600E or V600K mutated melanoma, offering a progression-free survival and overall survival advantage compared to chemotherapy.

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

16.

Success of rechallenging dabrafenib and trametinib combination therapy after trametinib-induced rhabdomyolysis: a case report.

Author: MutoYusuke, NgWilliam, NamikawaKenjiro, TakahashiAkira, TsutsumidaArata, NishidaMakiko, YamazakiNaoya

Melanoma treatment
Rhabdomyolysis

A combination therapy of dabrafenib and trametinib was effective for BRAF-mutant advanced melanomas, but a rare adverse event of rhabdomyolysis was reported.

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.

Extraordinary clinical benefit to sequential treatment with targeted therapy and immunotherapy of a BRAF V600E and PD-L1 positive metastatic lung adenocarcinoma.

Author: LiShuyu D, MartialAnnia, SchrockAlexa B, LiuJane J

NSCLC treatment

This abstract discusses the question of whether targeted therapy should be used before immunotherapy in patients with metastatic non-small cell lung cancer (NSCLC) harboring both BRAF V600E and PD-L1 expression.

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

18.

Potential drug-drug interactions with mitogen-activated protein kinase (MEK) inhibitors used to treat melanoma.

Author: MaraniA, GioacchiniH, PaolinelliM, OffidaniA, CampanatiA

Targeted therapy for melanoma
Drug interactions
Increased toxicity

This review examines drug-drug interactions associated with MEK inhibitors, which are used for the treatment of BRAF-mutated advanced melanoma. The review highlights the potential benefits and increased toxicity of these interactions, emphasizing the need for careful medication management in this patient population.

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

19.

Ocular side effects of target therapy and immunotherapy in patients with cutaneous malignant melanoma.

Author: EikenberryJennifer, HarrisAlon, TorabiRana, LangMatthew, DenneyDerek, Verticchio VercellinAlice, SieskyBrent

CMM treatment
Ocular side effects

Systemic target therapy with BRAF and MEK inhibitors and immunotherapy with CTLA-4 and PD-1 monoclonal antibodies may cause ocular side effects.

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

Language : English

20.

Trametinib and dabrafenib induced rhabdomyolysis, renal failure, and visual loss. Report of one case.

Author: FinstererJosef

BRAF-mutated melanoma treatment
Diarrhea
Fever
Inactivity
Loss of appetite
Myoglobinuria
Ocular muscle weakness
Tiredness
Vertigo
Visual impairment
Visual loss
Vomiting

This case report describes a patient with BRAF-mutated metastatic melanoma who developed severe side effects after starting trametinib and dabrafenib, including visual loss and myoglobinuria. The patient discontinued treatment and experienced almost complete remission of the deficits.

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

21.

Biomarker and Tumor Responses of Oral Cavity Squamous Cell Carcinoma to Trametinib: A Phase II Neoadjuvant Window-of-Opportunity Clinical Trial.

Author: UppaluriRavindra, WinklerAshley E, LinTianxiang, LawJonathan H, HaugheyBruce H, NussenbaumBrian, PanielloRandal C, RichJason T, DiazJason A, MichelLoren P, WildesTanya, DunnGavin P, ZolkindPaul, KallogjeriDorina, PiccirilloJay F, DehdashtiFarrokh, SiegelBarry A, ChernockRebecca D, LewisJames S, AdkinsDouglas R

Reduced Ras/MEK/ERK activation
Tumor response
Constipation
Duodenal perforation
Nausea
Rash

This study investigated the potential of trametinib, a MEK inhibitor, as a neoadjuvant therapy for oral cavity squamous cell carcinoma (OCSCC). The study found that trametinib significantly reduced the activation of the Ras/MEK/ERK pathway and resulted in clinical and metabolic tumor responses in patients with OCSCC. However, trametinib was associated with adverse events such as rash, nausea, and duodenal perforation.

Clinical Trial, Phase IIA Phase II trial is a trial that further evaluates the efficacy and safety of a new drug or treatment, whose safety has been confirmed to some extent in a Phase I trial, in a small number of patients.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.

Language : English

22.

BRAF inhibitors stimulate inflammasome activation and interleukin 1 beta production in dendritic cells.

Author: HajekEva, KrebsFranziska, BentRebekka, HaasKatharina, BastAntje, SteinmetzIvo, TuettenbergAndrea, GrabbeStephan, BrosMatthias

Melanoma treatment
Tumor immune response
Inflammasome activation
Pro-inflammatory side effects

BRAF<sup>V600E</sup> inhibitors, Vemurafenib (VEM) and Dabrafenib (DAB), were found to modulate dendritic cell (DC) function and induce IL-1β release. DAB, to a greater extent than VEM, activated the NLRC4/Caspase-1 inflammasome in mouse and human DCs.

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

Language : English

23.

Severe Epistaxis Secondary to Dabrafenib and Trametinib Toxicity in Non-small Cell Lung Carcinoma With Small Bowel Metastasis.

Author: GullapalliKeerthi, MosalemOsama, VargheseMerryl T, WatatKevin, HrinczenkoBorys

BRAF-positive lung cancer
NSCLC treatment
Hemorrhage

Dabrafenib and trametinib, a combination therapy for BRAF-mutant NSCLC, can lead to severe and life-threatening bleeding. This case report highlights the importance of awareness of this 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.

Language : English

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