Effects of ceritinib: A Synthesis of Findings from 26 Studies

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Original Abstract of the Article

Major Research Findings

Ceritinib is a tyrosine kinase inhibitor that is effective in treating non-small cell lung cancer (NSCLC) with anaplastic lymphoma kinase (ALK) gene rearrangements. 2 suggests that ceritinib may be an effective treatment for brain metastases in ALK-positive NSCLC. 16 suggests that ceritinib inhibits the activity of the organic cation transporter 3 (OCT3), which could affect the metabolism of other drugs. 12 suggests that ceritinib, when combined with AKT inhibitors, may increase their effectiveness against gastric cancer cells. 6 suggests that ceritinib activates LC3B-independent, protective autophagy in EML4-ALK positive lung cancer cells, which might contribute to cancer cell survival. 11 suggests that ceritinib, unlike imatinib, causes a significant disturbance of lipid membrane integrity, which could lead to cell toxicity. These studies suggest that ceritinib is a promising drug for the treatment of ALK-positive NSCLC, but it is important to consider the potential side effects and drug interactions.

Ceritinib has shown effectiveness against patients with ALK gene rearrangements in NSCLC who have developed resistance to crizotinib. 3 compares the efficacy of ceritinib and alectinib in patients with advanced NSCLC with ALK gene rearrangements who failed crizotinib treatment. This study suggests that ceritinib may be more effective than alectinib in patients who are resistant to crizotinib. 17 suggests that ceritinib, in combination with gemcitabine-based chemotherapy, may be effective for the treatment of advanced solid tumors. These studies suggest that ceritinib is an effective drug for ALK-positive NSCLC patients who have developed resistance to crizotinib.

Benefits and Risks

Benefit Summary

Ceritinib is an effective drug for the treatment of non-small cell lung cancer with anaplastic lymphoma kinase (ALK) gene rearrangements. It has shown effectiveness against patients who have developed resistance to crizotinib. Ceritinib also has the potential to enhance the effectiveness of other drugs when used in combination.

Risk Summary

Ceritinib has the risk of side effects. Some of the side effects include hyperglycemia, liver dysfunction, kidney dysfunction, nausea, vomiting, diarrhea, and fatigue. Ceritinib can also affect the metabolism of other drugs.

Comparison of Studies

Similarities of Studies

Multiple studies have shown that ceritinib is effective in the treatment of non-small cell lung cancer with anaplastic lymphoma kinase (ALK) gene rearrangements. Studies have also shown that ceritinib has the potential to enhance the effectiveness of other drugs when used in combination.

Differences of Studies

Studies on the efficacy of ceritinib vary in their target patient populations and evaluation methods. Therefore, it is important to interpret the results with caution. For example, 3 compares the efficacy of ceritinib and alectinib in patients with advanced NSCLC with ALK gene rearrangements who failed crizotinib treatment, whereas 17 suggests that ceritinib, in combination with gemcitabine-based chemotherapy, may be effective for the treatment of advanced solid tumors. These studies highlight different perspectives on the evaluation of ceritinib’s efficacy.

Consistency and Contradictions of Results

Multiple research findings suggest that ceritinib is an effective drug for the treatment of non-small cell lung cancer with anaplastic lymphoma kinase (ALK) gene rearrangements. However, further research is needed on the risks of side effects and drug interactions.

Points to Note for Real-Life Applications

Ceritinib is an effective drug for the treatment of non-small cell lung cancer with anaplastic lymphoma kinase (ALK) gene rearrangements, but it has the risk of side effects. When using ceritinib, it is important to follow the doctor's instructions and monitor for any side effects.

Limitations of Current Research

The studies on the efficacy of ceritinib are limited by the size of the patient population and the evaluation methods. Therefore, more research is needed. Furthermore, the risks of side effects and drug interactions are not yet fully understood.

Future Research Directions

To further evaluate the efficacy and safety of ceritinib, larger clinical trials with more patients are needed. Research is also necessary to mitigate the risks of side effects and drug interactions. Additionally, research is important to better understand the mechanism of action of ceritinib.

Conclusion

Ceritinib is a promising drug for the treatment of non-small cell lung cancer with anaplastic lymphoma kinase (ALK) gene rearrangements. However, it is important to consider the risks of side effects and drug interactions. When using ceritinib, it is important to follow the doctor's instructions and monitor for any side effects.

Keywords
Benefit Keywords
Apoptosis induction
Growth inhibition
Potent anticancer effects
1
Effective treatment
Improved survival
2
ALK-positive NSCLC
CNS protection
3
NSCLC treatment
4
Ceritinib for ALCL
5
Improved anticancer activity
7
OS improvement
8
IMT treatment advancement
Targeted therapy development
9
ALK-positive NSCLC treatment
Extended quality of life
Viable treatment options
10
Cancer treatment
11
Gastric cancer treatment
12
Effective NSCLC treatment
13
Improved treatment
Long-term survival
15
ALK/ROS1 inhibition
17
NSCLC treatment
18
NSCLC treatment
19
ALK inhibition
Cancer cell proliferation inhibition
20
Lung cancer treatment
21
ALK/ROS1 inhibition
Cancer treatment
23
Lung cancer treatment
24
ALK inhibition
Improved survival for NSCLC patients
26
Risk Keywords
ALK inhibitor side effects
2
crizotinib failure
3
NSCLC
drug resistance
4
Drug resistance
7
Bias
8
Clinically relevant toxicities
High prevalence of dose modifications
10
Apoptosis
Cell lysis
11
Ceritinib side effects
13
ALK-TKI side effects
Anemia
Cognitive effects
Constipation
Diarrhea
Edema
Elevated liver enzymes
Fatigue
Gastrointestinal reactions
Hepatotoxicity
Increased creatinine
Lipid level changes
Mood effects
Neutropenia
Skin disorders
Visual disorders
Weight gain
14
Relapse risk
Resistance
15
Drug-drug interactions
Toxicity
16
Constitutional toxicity
Gastrointestinal toxicity
Hematologic toxicity
17
Hepatobiliary adverse effects
18
Kidney failure
Peripheral edema
Renal cysts
19
Hyperglycemia
21
Myasthenia gravis
Photosensitivity reactions
Pneumothorax
Pulmonary arterial hypertension
Rectal perforation
22
Thyroid dysfunction
25
Adverse drug reactions
26
Literature analysis of 26 papers
Positive Content
23
Neutral Content
1
Negative Content
2
Article Type
0
1
1
6
23
2.

[Research Progress in the Efficacy and Safety of ALK Inhibitors 
in the Treatment of NSCLC Brain Metastasis].

Author: ChenYuchen, HanHan, WeiJinpan, DuQianyu, WangXiyong

Effective treatment
Improved survival
ALK inhibitor side effects

This review summarizes the efficacy and safety of anaplastic lymphoma kinase (ALK) inhibitors in treating brain metastases in ALK-positive non-small cell lung cancer (NSCLC) patients. The review provides clinical guidance on selecting the appropriate ALK inhibitor based on its generation and specific benefits for treating brain metastases.

ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.
English AbstractA summary of a research paper/publication written in English for a wider audience.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.

Language : Chinese

3.

A retrospective study of alectinib versus ceritinib in patients with advanced non-small-cell lung cancer of anaplastic lymphoma kinase fusion in whom crizotinib treatment failed.

Author: KuoChih-Hsi Scott, TungPi-Hung, HuangAllen Chung-Cheng, WangChin-Chou, ChangJohn Wen-Cheng, LiuChien-Ying, ChungFu-Tsai, FangYueh-Fu, GuoYi-Ke, YangCheng-Ta

ALK-positive NSCLC
CNS protection
crizotinib failure

Second-generation ALK inhibitors, alectinib and ceritinib, showed satisfactory efficacy in patients with ALK-positive advanced NSCLC who failed crizotinib treatment. Alectinib demonstrated greater central nervous system (CNS) protection and higher progression-free survival (PFS) in patients whose cause of crizotinib failure was intolerance.

Comparative StudyResearch that compares multiple groups/interventions to determine differences/similarities in outcomes/characteristics.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.

Language : English

4.

Short-term response to immune-chemotherapy and immune features of a ceritinib-resistant patient with <i>ROS1</i>-rearranged lung adenocarcinoma.

Author: YueDongsheng, QianJuanjuan, ChenZhipeng, ZhangBin, ChenPeng, ZhangLei, LiJingjing, ZhangHenghui, WangChangli

NSCLC treatment
NSCLC
drug resistance

A patient with <i>ROS1</i>-rearranged lung adenocarcinoma, resistant to ceritinib, benefited from lorlatinib therapy. Immune-chemotherapy with nivolumab plus chemotherapy showed initial partial response but limited long-term benefit, highlighting the need for monitoring immune factors.

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.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

5.

Precision therapy with anaplastic lymphoma kinase inhibitor ceritinib in ALK-rearranged anaplastic large cell lymphoma.

Author: SubbiahV, KuraviS, GangulyS, WelchD R, VivianC J, MushtaqM U, HegdeA, IyerS, BehrangA, AliS M, MadisonR W, VenstromJ M, JensenR A, McGuirkJ P, AminH M, BalusuR

Ceritinib for ALCL

Ceritinib, a drug that targets the ALK fusion kinase, showed promising preclinical and clinical efficacy in treating NPM1-ALK+ ALCL. In vitro studies showed that ceritinib inhibited the activity of the fusion kinase and induced apoptosis in lymphoma cell lines. In a xenograft model, ceritinib led to tumor regression and improved survival. A patient with multiple relapses of NPM1-ALK+ ALCL achieved complete remission with ongoing clinical benefit after receiving ceritinib treatment.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, N.I.H., ExtramuralResearch funding provided by the NIH to external research institutions and researchers.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.
Research Support, U.S. Gov't, Non-P.H.S.Research funding provided by US government agencies other than the Public Health Service.

Language : English

9.

Inflammatory myofibroblastic tumor: molecular landscape, targeted therapeutics, and remaining challenges.

Author: MahajanPriya, CasanovaMichela, FerrariAndrea, FordhamAshleigh, TrahairToby, VenkatramaniRajkumar

IMT treatment advancement
Targeted therapy development

This review discusses the molecular characteristics, evolution of targeted therapies, and remaining challenges in the management of inflammatory myofibroblastic tumor (IMT), a rare mesenchymal tumor.

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.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.

Language : English

10.

Real-World Treatment Sequencing, Toxicities, Health Utilities, and Survival Outcomes in Patients with Advanced ALK-Rearranged Non-Small-Cell Lung Cancer.

Author: SchmidSabine, ChengSierra, ChotaiSimren, GarciaMiguel, ZhanLuna, HuenikenKatrina, BalaratnamKarmugi, KhanKhaleeq, PatelDevalben, GrantBenjamin, RaptisRoula, BrownM Catherine, XuWei, MoriartyPatrick, ShepherdFrances A, SacherAdrian G, LeighlNatasha B, BradburyPenelope A, LiuGeoffrey

ALK-positive NSCLC treatment
Extended quality of life
Viable treatment options
Clinically relevant toxicities
High prevalence of dose modifications

Serial ALK-TKI sequencing approaches are a viable therapeutic option for patients with advanced-stage ALK-positive NSCLC, extending quality of life. While clinically relevant toxicities were observed across all ALK-TKIs, treatment modifications did not negatively impact outcomes. Further research is needed to determine the optimal sequencing approach for these patients.

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

11.

The small-molecule kinase inhibitor ceritinib, unlike imatinib, causes a significant disturbance of lipid membrane integrity: A combined experimental and MD study.

Author: FischerMarkus, LuckMeike, WerleMax, VogelAlexander, BashawatMohammad, LudwigKai, ScheidtHolger A, MüllerPeter

Cancer treatment
Apoptosis
Cell lysis

This study investigated the interaction of ceritinib and imatinib, protein kinase inhibitors, with lipid membranes. Ceritinib was found to interact more strongly with membranes, potentially impacting its safety and efficacy.

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

Language : English

14.

Comparative safety of anaplastic lymphoma kinase tyrosine kinase inhibitors in advanced anaplastic lymphoma kinase-mutated non-small cell lung cancer: Systematic review and network meta-analysis.

Author: LuoYuyao, ZhangZhe, GuoXuanZhu, TangXuemei, LiSijie, GongGuotao, GaoShun, ZhangYan, LinSheng

ALK-TKI side effects
Anemia
Cognitive effects
Constipation
Diarrhea
Edema
Elevated liver enzymes
Fatigue
Gastrointestinal reactions
Hepatotoxicity
Increased creatinine
Lipid level changes
Mood effects
Neutropenia
Skin disorders
Visual disorders
Weight gain

The toxicity profiles of six ALK-TKIs differed significantly. Alectinib might be the safest ALK-TKI drug based on the combined evidence of grades 3-4 AEs and the combined incidence.

Meta-AnalysisA statistical technique that integrates the results of multiple studies to draw more general conclusions about a particular issue.
Systematic ReviewA review that systematically collects, evaluates, and integrates relevant research to answer a specific research question.
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

17.

A phase I study of the anaplastic lymphoma kinase inhibitor ceritinib in combination with gemcitabine-based chemotherapy in patients with advanced solid tumors.

Author: FountzilasChristos, AdjeiAlex, OpyrchalMateusz, EvansRachel, GhasemiMohammad, AttwoodKristopher, GromanAdrienne, BsharaWiam, GoeyAndrew, WiltonJohn, MaWen Wee, IyerRenuka

ALK/ROS1 inhibition
Constitutional toxicity
Gastrointestinal toxicity
Hematologic toxicity

Ceritinib, an ALK/ROS1 inhibitor, combined with gemcitabine-based chemotherapy has a manageable toxicity profile. The maximum tolerated dose of ceritinib was 600 mg with gemcitabine and 450 mg daily with gemcitabine/cisplatin. The combination showed a 20% overall response rate and a median progression-free survival of 4.8 months. Further development in tumors with ALK or ROS1 fusions is warranted.

Clinical Trial, Phase IThe first stage of clinical trials in humans. Evaluates the safety, tolerability, and pharmacokinetics of a new drug/treatment.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, N.I.H., ExtramuralResearch funding provided by the NIH to external research institutions and researchers.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

18.

Possible involvement of interleukin-18 in the pathology of hepatobiliary adverse effects related to treatment with ceritinib.

Author: HiranoTaizou, KoaraiAkira, IchikawaTomohiro, SatoTeruyuki, OheTakashi, IchinoseMasakazu

NSCLC treatment
Hepatobiliary adverse effects

Increased serum IL-18 is being investigated as a potential biomarker for hepatobiliary adverse effects related to ceritinib treatment in patients with ALK-positive non-small cell lung cancer.

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

19.

Anaplastic lymphoma kinase inhibitors and their effect on the kidney.

Author: BonillaMarco, JhaveriKenar D, IzzedineHassan

NSCLC treatment
Kidney failure
Peripheral edema
Renal cysts

This review provides an update on the kidney-related side effects of ALK inhibitors, such as crizotinib, ceritinib, and alectinib, used for treating non-small-cell lung cancer (NSCLC) patients with ALK gene rearrangement. Treatment with ALK inhibitors may lead to peripheral edema, electrolyte disorders, kidney failure, proteinuria, and an increased risk of renal cysts.

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

20.

Pyrroformyl-containing 2,4-diaminopyrimidine derivatives as a new optimization strategy of ALK inhibitors combating mutations.

Author: CaoMeng, ChenYuxiang, ZhaoTianming, WeiShangfei, GuoMing, ZhaiXin

ALK inhibition
Cancer cell proliferation inhibition

Compound 11k, a pyrroformyl-containing 2,4-diaminopyrimidine, showed potent anti-proliferative activity against H2228 cells and effectively inhibited ALK<sup>WT</sup> and ALK<sup>L1196M</sup> enzymes. This compound holds promise as a potential ALK inhibitor for treating ALK-mutation-driven cancers.

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

24.

Safety and activity of alectinib plus bevacizumab in patients with advanced ALK-rearranged non-small-cell lung cancer: a phase I/II study.

Author: LinJ J, MuzikanskyA, KennedyE, KuberskiH, StoberL L, WanatA C, AzzoliC G, LennesI, SequistL V, Dagogo-JackI, ShawA T, GainorJ F

Lung cancer treatment

Alectinib, a drug for advanced lung cancer, is effective but resistance develops. This study investigated the safety and effectiveness of combining alectinib with bevacizumab, an antibody, to potentially delay resistance.

Clinical Trial, Phase IThe first stage of clinical trials in humans. Evaluates the safety, tolerability, and pharmacokinetics of a new drug/treatment.
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.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

26.

Expert consensus of management of adverse drug reactions with anaplastic lymphoma kinase tyrosine kinase inhibitors.

Author: ZhouF, YangY, ZhangL, ChengY, HanB, LuY, WangC, WangZ, YangN, FanY, WangL, MaZ, YaoY, ZhaoJ, DongX, ZhuB, ZhouC

ALK inhibition
Improved survival for NSCLC patients
Adverse drug reactions

ALK rearrangements are found in about 3%-6% of patients with advanced non-small-cell lung cancer. ALK tyrosine kinase inhibitors (ALK-TKIs) are effective in treating these patients but can cause a range of side effects. This article summarizes the incidence, diagnosis, and treatment of adverse drug reactions (ADRs) caused by ALK-TKIs in China.

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

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