TOXICITIES OF TARGETED THERAPY AND IMMUNE-RELATED ADVERSE DRUG REACTIONS OF IMMUNOTHERAPY IN THE TREATMENT OF METASTATIC MELANOMA

2018 ◽  
Author(s):  
Lidija Kandolf Sekulović
Keyword(s):  
Overall Survival ◽  
Targeted Therapy ◽  
Side Effects ◽  
Adverse Effects ◽  
Metastatic Melanoma ◽  
Adverse Drug Reactions ◽  
Mek Inhibitor ◽  
Braf Inhibitors ◽  
Drug Reactions ◽  
Acneiform Eruption

Targeted therapy and immunotherapy changed the treatment landscape for metastatic melanoma, which is chemotherapy resistant cancer. In pre-innovation era, the overall survival of patients with metastatic melanoma was 6 months, while today 5-year overall survival rate of 34% (and 50% in good prognostic groups) is evident. However, both treatments have their side effects, and cutaneous are the most frequent. Treating physicians in oncology centres, but also primary care specialists, need to be aware of their spectrum which differs for each class of drug: BRAF inhibitors, MEK inhibitors and immunotherapy with anti-PD1 and anti-CTLA4. While BRAF inhibitors have the most prominent adverse effects which are class specific, there are also drug-specific adverse effects. For example, vemurafenib causes photosensitivity, which is not specific for dabrafenib, while dabrafenib induces pyrexia, that occurs much less frequently with other BRAF inhibitors. Cutaneous rash and cutaneous neoplasms which develop due to paradoxical activation of RAS signalling are described with BRAF inhibitor monotherapy. These side-effects are much less common in combination therapy with BRAF and MEK inhibitor, but MEK inhibitor itself causes characteristic acneiform eruption, and serous retinopathy. Immune related adverse drug reactions are a hallmark of the immune checkpoint inhibitor immunotherapy, which can affect every organ system, and most commonly skin, lungs and gastrointestinal system, with differential frequencies recorded with anti-CTLA4 therapy and anti PD-1 therapy. Skin reactions most frequently include pruritus and eczematous reactions, as well as vitiligo-like hypopigmentation, which is linked Melanom 45 to the better response to treatment. In this review, frequent and rare side effects are presented, as well as the current algorithms for their treatment.

Prospective Case Series of Cutaneous Adverse Effects Associated With Dabrafenib and Trametinib

2016 ◽  
Vol 21 (1) ◽  
pp. 54-59 ◽  
Author(s):  
Jean-Philip Lacroix ◽  
Beatrice Wang
Keyword(s):  
Side Effects ◽  
Adverse Effects ◽  
Metastatic Melanoma ◽  
Case Series ◽  
Braf Inhibitor ◽  
Mek Inhibitor ◽  
Braf V600e ◽  
Cutaneous Toxicity ◽  
Palmoplantar Hyperkeratosis ◽  
Acneiform Eruption

Background: Dabrafenib, a novel selective small-molecule inhibitor of BRAF, has been shown to increase overall survival in patients with unresectable metastatic melanoma harboring the BRAF V600E mutation. The development of resistance has led to combination therapy with selective MEK inhibitor trametinib. Compared with vemurafenib, dabrafenib is a more recent BRAF inhibitor approved by the Food and Drug Administration in May 2013 for metastatic melanoma; fewer data are available in the current literature regarding cutaneous toxicity. Objectives: We sought to present additional cutaneous side effects of dabrafenib and trametinib and follow their evolution and management. Methods: We carried out a prospective study of 14 patients treated with dabrafenib alone or with trametinib. Patients were followed every 4 weeks, and we collected detailed cutaneous symptoms, photos, and biopsy specimens. Results: All patients presented with at least 1 adverse skin reaction. The mean duration of treatment was 24 weeks. The most common adverse effect was papillomas (7/14), followed by palmoplantar hyperkeratosis (5/14), alopecia (5/14), and seborrheic dermatitis-like eruption (2/14). Three patients who received trametinib developed an acneiform eruption (3/5). One patient developed a keratoacanthoma-like squamous cell carcinoma. Side effects presented as early as 2 weeks after starting therapy, with a mean time of onset of 9 weeks. Conclusion: Selective BRAF inhibitor dabrafenib and MEK inhibitor trametinib are associated with multiple skin adverse effects. Given their recent approval and the potential for malignant lesions to develop on treatment, awareness of potential adverse effects and their management is necessary.

scholarly journals Cutaneous Side Effects of BRAF Inhibitors in Advanced Melanoma: Review of the Literature

2016 ◽  
Vol 2016 ◽  
pp. 1-6 ◽  
Author(s):  
Bilgen Gençler ◽  
Müzeyyen Gönül
Keyword(s):  
Side Effects ◽  
Metastatic Melanoma ◽  
Mapk Pathway ◽  
Case Reports ◽  
Mitogen Activated Protein Kinase ◽  
Braf V600e ◽  
Braf Inhibitors ◽  
Braf Mutations ◽  
Cutaneous Side Effects ◽  
Downstream Signaling

The incidence of melanoma has recently been increasing. BRAF mutations have been found in 40–60% of melanomas. The increased activity of BRAF V600E leads to the activation of downstream signaling through the mitogen-activated protein kinase (MAPK) pathway, which plays a key role as a regulator of cell growth, differentiation, and survival. The use of BRAF inhibitors in metastatic melanoma with BRAF mutation ensures clinical improvement of the disease. Vemurafenib and dabrafenib are two selective BRAF inhibitors approved by the Food and Drug Administration (FDA). Both drugs are well tolerated and successfully used in clinical practice. However, some adverse reactions have been reported in patients in the course of treatment. Cutaneous side effects are the most common adverse events among them with a broad spectrum. Both the case reports and several original clinical trials reported cutaneous reactions during the treatment with BRAF inhibitors. In this review, the common cutaneous side effects of BRAF inhibitors in the treatment of metastatic melanoma with BRAF V600E mutation were reviewed.

scholarly journals Analysis of Influence Factors of Quality of Life of Lung Cancer Patients with Skin Adverse Drug Reactions Under Targeted Therapy

2022 ◽  
Author(s):  
Ruofei Du ◽  
Xin Wang ◽  
Huiyue Zhou ◽  
Lixia Ma ◽  
Leon M. Larcher ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Lung Cancer ◽  
Targeted Therapy ◽  
Adverse Drug Reactions ◽  
Education Level ◽  
Self Management ◽  
Drug Reactions ◽  
The Status ◽  
Nsclc Patients

Abstract Purpose This study was to assess the status of quality of life and explore the possible factors correlated with quality of life among non-small cell lung cancer (NSCLC) patients with skin adverse drug reactions under targeted therapy. Methods We performed a cross-sectional study including 536 NSCLC patients with skin adverse drug reactions by targeted therapy in cancer outpatient clinics of three hospitals in China between May 2020 and May 2021. And we collected data with structured questionnaires and identified the relationships among coping style, self-management and quality of life by Pearson correlation analysis and multiple linear regression algorithm. Results The total score of quality of life was 46±12.84 in 536 NSCLC patients with skin adverse drug reactions undergoing targeted therapy. In multiple linear regression analysis, we identified the significant factors associated with quality of life including age, education level, combination of medicine, Charlson Comorbidity Index (CCI), stages of disease, facing, yield, symptom management, daily activity management, psychological and emotional management, self-efficacy and self-management (P < 0.05). Conclusions NSCLC patients with skin adverse drug reactions undergoing targeted therapy generally had a compromised quality of life. And the critical factors that affected the status of quality of life were age, education level, co-morbidity, the combinatorial application of drugs and stage of disease, self-management and coping styles.

scholarly journals Advanced melanoma, a pharmacological evaluation

2021 ◽  
Vol 31 (Supplement_2) ◽  
Author(s):  
Anabela Andrade ◽  
Jorge Balteiro
Keyword(s):  
Overall Survival ◽  
Targeted Therapy ◽  
Braf Inhibitor ◽  
Progression Free Survival ◽  
Mek Inhibitor ◽  
Advanced Melanoma ◽  
New Drugs ◽  
High Rate ◽  
Free Survival ◽  
Dismal Prognosis

Abstract Background Cutaneous melanoma is an aggressive cancer that occurs in melanocytes, located in the epidermis. Historically it has a high rate of morbidity and mortality, due to the resistance and toxicity of traditional therapies. Its incidence has increased annually by 4% to 8%. Until 2011 it was still considered a devastating and almost always fatal disease in a few months. Advances in therapies have significantly improved the results of most patients with advanced melanoma, especially those with a BRAFV600 mutation, which account for almost 50% of tumors. Before the recent evolution in treatment, the prognosis and overall survival were considered very bad. The introduction of new drugs has improved progression-free survival and overall survival, as well as producing faster clinical responses. Methods Comparison of endpoints such as progression-free survival and overall melanoma survival from the Summary of Product Characteristics (SPC) studies of each drug in the therapeutic groups under assessment used in the disease. The variables used were the Endpoints Global Survival at various times (12 months, 24 months, 36 months and the median) and Progression-Free Survival. Results Combined immunotherapy (Nivolumab and Ipilimumab) improves overall survival and progression-free survival, achieving better results than targeted therapy. In this, the combination of a BRAF inhibitor and a MEK inhibitor, presents better results with the combination of Encorafenib and Binimetinib. Conclusions Both targeted therapy and immunotherapy transform melanoma with a dismal prognosis into a life-threatening illness.

scholarly journals NEUROPSYCHIATRIC ADVERSE EFFECTS OF ANTIBACTERIAL AGENTS

2021 ◽  
pp. 1-8
Author(s):  
SANTA TREASA CYRIAC ◽  
DIVYA SARA IYPE
Keyword(s):  
Adverse Effects ◽  
Adverse Events ◽  
Adverse Drug Reactions ◽  
Bacterial Growth ◽  
Antibacterial Agents ◽  
Acute Psychosis ◽  
Drug Reactions ◽  
Medical Practitioners ◽  
General Management ◽  
Neuropsychiatric Adverse Effects

Anti-bacterial are agents that inhibit bacterial growth or kills bacteria and are a sub-type of antimicrobials. These are drugs used to treat infections, but they sometimes pose a threat of adverse events. Some of these adverse events are neuropsychiatric, which are generally hard to diagnose and is often paid less attention. They account for about 30% of total Adverse drug reactions (ADRs) caused by drugs in patients without mental abnormalities. The spectrum ranges from episodes of seizure to acute psychosis. The article emphasizes the frequency of such adverse events and means to raise awareness among medical practitioners regarding the same. The various neuropsychiatric adverse effects and the agents responsible have been reviewed, along with their possible mechanisms and general management. The information for writing this review was selected by searching for keywords such as Neurotoxicity, GABA, Psychosis, Naranjo scale, and Antibiomania in databases such as Google Scholar, PubMed, Elsevier, etc. After searching the articles in the above-mentioned databases, the articles were screened concerning their importance with our work and according to their title and abstract. Additional articles were discovered by checking the references in the current study's citations. Using this method, the various neuropsychiatric adverse effects of Antibacterial agents were summarized in this review.

Alopecia Associated with HMG-CoA Reductase Inhibitor; “Delayed, Recurrent” SIADH and SSRIs; Serious Adverse Effects with Acetazolamide; Tetany Associated with Proton Pump Inhibitor

2002 ◽  
Vol 37 (10) ◽  
pp. 1040-1042 ◽  
Author(s):  
Joel Shuster
Keyword(s):  
Proton Pump Inhibitor ◽  
Adverse Effects ◽  
Adverse Drug Reactions ◽  
Proton Pump ◽  
Reductase Inhibitor ◽  
Drug Reactions ◽  
Hmg Coa Reductase ◽  
Hmg Coa Reductase Inhibitor ◽  
Coa Reductase

The purpose of this feature is to heighten awareness of specific adverse drug reactions (ADRs), to discuss methods of prevention, and to promote reporting of ADRs to the FDA's medWatch program (800-FDA-1088). If you have reported an interesting preventable ADR to medWatch, please consider sharing the account with our readers.

scholarly journals Salutary Response to Targeted Therapy in Anaplastic Thyroid Cancer

2019 ◽  
Vol 7 ◽  
pp. 232470961989094 ◽  
Author(s):  
Sasan Fazeli ◽  
Edina Paal ◽  
Jessica H. Maxwell ◽  
Kenneth D. Burman ◽  
Eric S. Nylen ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Targeted Therapy ◽  
Side Effects ◽  
Combination Therapy ◽  
Braf Inhibitor ◽  
Anaplastic Thyroid Cancer ◽  
Mek Inhibitor ◽  
Braf V600e ◽  
Aggressive Tumor ◽  
Well Differentiated

Context. Anaplastic thyroid cancer (ATC) is an aggressive tumor with a median survival of 3 to 9 months, a 1-year survival of less than 10% and without definitive therapies. Recently, in BRAF V600E mutated ATCs, new targeted therapy using a combination of a BRAF inhibitor, dabrafenib (Dab), with a mitogen-activated extracellular protein kinase (MEK) inhibitor, trametinib (Tram), has shown significant promise. Case Description. We report a case of aggressive ATC with 5 sequence mutations: BRAF V600E (mutation fraction [MF] 34%), TERT E441del (MF 37%), RET N579K (MF 55%), EZH2 D154E (MF 60%), and CDK4 S259L (MF 48%). The patient had a dramatic response to the Dab/Tram combination with near complete resolution of his lung, bone, hepatic, and splenic lesions soon after starting therapy. Unfortunately, intolerable side effects (grade 2-3) on this regimen required tapering and discontinuation of the treatment. He had a quick resurgence of disease after stopping the combination therapy. The patient died approximately 3 months after discontinuing Dab/Tram. Autopsy revealed an atrophic thyroid gland with microscopic subcapsular focus of well-differentiated papillary thyroid carcinoma. There was extensive lymphatic spread of the tumor throughout bilateral lungs with fibrosis. No other metastatic site was identified. Conclusion. We report a unique case of ATC with 2 new mutations of EZH2 D154E and CDK S529L. This case exemplifies the significant promise Dab/Tram therapy holds, the potential side effects that limit their use, and autopsy findings status post use of this combination therapy.

scholarly journals Response to Ipilimumab/Nivolumab Rechallenge and BRAF Inhibitor/MEK Inhibitor Rechallenge in a Patient with Advanced Metastatic Melanoma Previously Treated with BRAF Targeted Therapy and Immunotherapy

2020 ◽  
Vol 2020 ◽  
pp. 1-6 ◽  
Author(s):  
Caitlyn N. Myrdal ◽  
Srinath Sundararajan
Keyword(s):  
Targeted Therapy ◽  
Metastatic Melanoma ◽  
Checkpoint Inhibitors ◽  
Single Agent ◽  
Objective Response ◽  
Braf Inhibitor ◽  
Mek Inhibitor ◽  
Optimal Sequencing ◽  
The Right

Little is known about the optimal sequencing of targeted therapy and immunotherapy in the treatment of patients with BRAFV600-mutated metastatic melanoma. BRAF/MEK inhibition often has the benefit of rapid disease regression; however, resistance is frequently seen with long-term use. Treatment with immune checkpoint inhibitors offers the potential for long-term response but displays a lower rate of objective response. The benefit of synergy between therapies is apparent; however, there is limited data regarding optimal sequencing in the treatment of advanced melanoma. We present the case of a 62-year-old gentleman with advanced BRAFV600-mutated melanoma who followed an unconventional treatment path. After progressing on single-agent vemurafenib, he had response to multiple modalities of immunotherapy before progression. After, he had a substantial response to multiple BRAF/MEK inhibitor rechallenges before developing resistance. The patient is now stable after a retrial of combination immunotherapy. Our case illustrates that with the right sequencing of therapy, meaningful clinical responses can be elicited with rechallenging of targeted therapy and immunotherapy in metastatic melanoma.

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