Effects of crizotinib: A Synthesis of Findings from 20 Studies

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Original Abstract of the Article

Major Research Findings

Crizotinib is a tyrosine kinase inhibitor that has been approved for the treatment of ALK-positive non-small cell lung cancer. 2 Crizotinib has been shown to be effective in treating ALK-positive non-small cell lung cancer, with studies showing that it can shrink tumors and extend survival time. 10 It can also be effective in treating other types of cancer with ALK fusion genes, including anaplastic large cell lymphoma and inflammatory myofibroblastic tumors (IMTs). 12 However, crizotinib can cause side effects, such as liver dysfunction, nausea, neutropenia, and QT prolongation, which can lead to treatment discontinuation or adjustment. 2 Crizotinib can also affect kidney function, as studies have shown that it can reduce creatinine-based estimates of glomerular filtration rate (GFR). 19 Therefore, it is important to monitor kidney function in patients receiving crizotinib. Crizotinib has been shown to cross the placenta and may affect the fetus, so it is not recommended for pregnant women. 13 Crizotinib is metabolized in the liver and primarily excreted in the urine and feces. 14 Researchers have investigated the effectiveness of using crizotinib in combination with other treatments, including temozolomide, radiotherapy, and afatinib. These studies suggest that crizotinib can be more effective when combined with these treatments. 15 , 18 , 5 Crizotinib has a better safety profile than chemotherapy in ALK-positive non-small cell lung cancer, even though toxicities leading to treatment withdrawal are present. Adverse effects were tackled by dose reduction, temporary withdrawal from treatment, and close monitoring. 2

Benefits and Risks

Benefit Summary

Crizotinib is a promising treatment for ALK-positive non-small cell lung cancer, with potential to shrink tumors and extend survival time. Crizotinib has also shown promise in treating other cancers with ALK fusion genes, such as anaplastic large cell lymphoma and inflammatory myofibroblastic tumors (IMTs). Combining crizotinib with other therapies, such as temozolomide, radiotherapy, and afatinib, can potentially improve its effectiveness. Crizotinib has been shown to have a better safety profile than chemotherapy.

Risk Summary

Crizotinib can cause side effects, such as liver dysfunction, nausea, neutropenia, and QT prolongation. It can also affect kidney function. Crizotinib crosses the placenta and may affect the fetus, so it is not recommended for pregnant women. It is important to avoid combining crizotinib with certain medications, such as CYP3A inhibitors and CYP3A inducers.

Comparison of Studies

Similarities Across Studies

Many studies have shown that crizotinib is an effective treatment for ALK-positive non-small cell lung cancer. The research suggests that crizotinib can reduce tumor size and prolong survival time.

Differences Across Studies

The effectiveness of crizotinib may vary depending on the type of tumor and the specific genetic mutation present in the patient. Crizotinib can cause different side effects in different patients.

Consistency and Contradictions in Results

The results of multiple studies consistently show that crizotinib is an effective treatment for ALK-positive non-small cell lung cancer. However, the effectiveness of crizotinib can vary depending on the patient's specific tumor type and genetic mutations. Additionally, crizotinib can cause a range of side effects, and the severity of these side effects may vary between patients.

Points to Consider for Real-World Application

While crizotinib is a promising treatment for ALK-positive non-small cell lung cancer, it is important to carefully consider the potential side effects and risks before starting treatment. It is also important to monitor the patient's condition and adjust the treatment plan as needed.

Limitations of Current Research

The current research on crizotinib is still ongoing and more studies are needed to further understand its long-term effects and safety. More research is also needed to develop optimal dosing strategies and combination therapies to maximize the effectiveness of crizotinib.

Future Research Directions

Future research on crizotinib should focus on the following areas: * Long-term assessment of crizotinib's effectiveness and safety * Development of optimal dosing strategies and combination therapies for crizotinib * Elucidation of the mechanisms of resistance to crizotinib

Conclusion

Crizotinib is a promising treatment for ALK-positive non-small cell lung cancer, with the potential to shrink tumors and extend survival time. While crizotinib has a better safety profile than chemotherapy, it is important to carefully consider the potential side effects and risks before starting treatment. More research is needed to further understand the long-term effects and safety of crizotinib, and to develop optimal dosing strategies and combination therapies to maximize its effectiveness.

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

Different effects of crizotinib treatment in two non-small cell lung cancer patients with SDC4::ROS1 fusion variants.

Author: OhishiYuta, NakanishiYoko, HirotaniYukari, SuzukiAtsuko, TaninoTomoyuki, Nishimaki-WatanabeHaruna, KobayashiHiroko, NozakiFumi, OhniSumie, TangXiaoyan, HayashiKentaro, NakagawaYoshiko, ShimizuTetsuo, TsujinoIchiro, TakahashiNoriaki, GonYasuhiro, MasudaShinobu

Crizotinib response
ROS1 overexpression

This study investigates the clinicopathological differences between two SDC4::ROS1 positive NSCLC cases with different responses to crizotinib. It suggests that the activation of ROS1 signaling, dependent on ROS1 and pERK1/2 overexpression, may influence the response to crizotinib, even with the same ROS1 fusion partner.

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

Language : English

2.

Adverse Side Effects of Crizotinib in the Treatment of Anaplastic Lymphoma Kinase-Mutated Non-small Cell Lung Cancer: A Systematic Review.

Author: GeorgeSherie, ShahiSrushti R, AliZahra, AbazaAbdelrahman, JamilAneeque, GutlapalliSai Dheeraj, AliMarya, ObleMrinal J P, SoniaShamsun Nahar, HamidPousette

Improved side effect profile
Targeted therapy
Liver dysfunction
Nausea
Neutropenia
QT prolongation

Crizotinib is an ALK inhibitor used to treat ALK-mutated advanced NSCLC. While it has a better side effect profile than chemotherapy, it can still cause side effects such as liver dysfunction, nausea, neutropenia, and QT prolongation. These side effects can lead to treatment discontinuation or dose reduction.

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.

MgIG exerts therapeutic effects on crizotinib-induced hepatotoxicity by limiting ROS-mediated autophagy and pyroptosis.

Author: LiMin, WangChenxiang, YuZheng, LanQin, XuShaolin, YeZhongjiang, LiRongqi, YingLili, ZhangXiuhua, ZhouZiye

Lung cancer treatment
Hepatic toxicity

Crizotinib (CRIZO), used to treat non-small-cell lung cancer, can cause hepatic inflammatory injury, limiting its clinical use. This study suggests that CRIZO promotes autophagy activation and pyroptosis via ROS accumulation and that magnesium isoglycyrrhizinate (MgIG) may offer therapeutic effects by reducing ROS levels and protecting against CRIZO-induced hepatotoxicity.

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

4.

Crizotinib and ceritinib trigger immunogenic cell death via on-target effects.

Author: PetrazzuoloAdriana, Perez-LanzonMaria, LiuPeng, MaiuriM Chiara, KroemerGuido

ALK-rearranged lymphoma treatment

Low-dose ALK inhibitors, crizotinib and ceritinib, may stimulate immunogenic cell death (ICD) in anaplastic large cell lymphoma, suggesting on target ICD-promoting effects.

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

5.

Inhibiting insulin and mTOR signaling by afatinib and crizotinib combination fosters broad cytotoxic effects in cutaneous malignant melanoma.

Author: DasIshani, ChenHuiqin, MaddaloGianluca, TuominenRainer, RebeccaVito W, HerlynMeenhard, HanssonJohan, DaviesMichael A, Egyházi BrageSuzanne

CMM treatment
Resistance to treatment

While current treatments for disseminated cutaneous malignant melanoma (CMM) improve survival, disease progression is common. This study found that a combination of afatinib and crizotinib effectively suppressed mTOR and insulin signaling pathways, inhibiting CMM growth both in vitro and in vivo. This combination showed potential as a new therapeutic approach for CMM.

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

6.

The synthesis of a novel Crizotinib heptamethine cyanine dye conjugate that potentiates the cytostatic and cytotoxic effects of Crizotinib in patient-derived glioblastoma cell lines.

Author: ChoiPeter J, CooperElizabeth, SchwederPatrick, MeeEdward, FaullRichard, DennyWilliam A, DragunowMike, ParkThomas I-H, JoseJiney

Glioblastoma treatment

This study describes a drug-dye conjugate (1) of Crizotinib, an anaplastic lymphoma kinase inhibitor, and IR-786, a heptamethine cyanine dye. Conjugate 1 showed potent cytotoxic activity with nanomolar potency in glioblastoma cell lines and a dramatic improvement over Crizotinib alone. This research suggests that similar conjugates may be promising treatments for glioblastoma.

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

8.

Renal Effects of Crizotinib in Patients With ALK-Positive Advanced NSCLC.

Author: CamidgeD Ross, KimElizabeth E, UsariTiziana, PolliAnna, LewisIona, WilnerKeith D

Reversible renal changes
Decreased renal function

Crizotinib, a drug for anaplastic lymphoma kinase-positive advanced non-small cell lung cancer (NSCLC), led to a decrease in creatinine-based estimates of renal function mostly during the first two weeks of treatment. However, these changes were largely reversible following treatment discontinuation, suggesting that the effect may be on creatinine secretion rather than true nephrotoxicity.

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

9.

Comparison of cardiovascular effects of crizotinib and chemotherapy in ALK-positive advanced non-small-cell lung cancer.

Author: WilnerKeith D, UsariTiziana, PolliAnna, KimElizabeth E

cardiac function
none

Crizotinib did not reveal any clinically meaningful changes in myocardial function in patients with ALK-positive non-small-cell lung cancer.

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

10.

Effects of Treatment with Crizotinib on Non-small Cell Lung Carcinoma with ALK Translocation in the Czech Republic.

Author: MilošPešek, JanaSkřičková, VítězslavKolek, MonikaŠatánková, LeonaKoubková, JaromírRoubec, RenataChloupková, MarkétaČernovská, AndreaBenejová, JurajKultan, MichalHrnčiarik, MiladaZemanová, MarekKonečný, HelenaČoupková, MartinSvatoň

Treatment of ALK-positive NSCLC

This study investigated the effects of crizotinib in patients with advanced anaplastic lymphoma kinase (ALK) -positive non-small cell lung cancer (NSCLC). Crizotinib was effective in treating patients with advanced ALK-positive NSCLC.

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

Language : English

11.

Effects of crizotinib on creatinine clearance and renal hemodynamics.

Author: Meijer-SchaapLysbert, Van PuttenJohn W G, JanssenWilbert M T

Not applicable
Nephrotoxicity

Crizotinib treatment may increase glomerular pressure, potentially increasing the risk of long-term nephrotoxicity.

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

Language : English

12.

Long-term effects of crizotinib in ALK-positive tumors (excluding NSCLC): A phase 1b open-label study.

Author: Gambacorti-PasseriniCarlo, OrlovSergey, ZhangLi, BraitehFadi, HuangHuiqiang, EsakiTaito, HoribeKeizo, AhnJin-Seok, BeckJoseph T, EdenfieldWilliam Jeffrey, ShiYuankai, TaylorMatthew, TamuraKenji, Van TineBrian A, WuShang-Ju, PaoliniJolanda, SelaruPaulina, KimTae Min

ALK-positive lymphoma treatment
IMT treatment
Diarrhea
Vision disorders

Crizotinib, a drug that targets the ALK, MET, and ROS1 proteins, showed strong and durable activity in patients with ALK-positive lymphoma and inflammatory myofibroblastic tumors (IMTs). In a phase 1b study, 53% of lymphoma patients and 67% of IMT patients achieved a response, with a median treatment duration of almost 3 years. The most common side effects were diarrhea and vision disorders, mainly grade 1.

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.
Multicenter StudyResearch conducted in collaboration with multiple research institutions. It aims to collect a wide range of data and obtain more generalizable results.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

15.

Synergistic Effects of Crizotinib and Temozolomide in Experimental FIG-ROS1 Fusion-Positive Glioblastoma.

Author: DasArabinda, ChengRon Ron, HilbertMegan L T, Dixon-MohYaenette N, DecandioMichele, VandergriftWilliam Alex, BanikNaren L, LindhorstScott M, CachiaDavid, VarmaAbhay K, PatelSunil J, GiglioPierre

GB treatment

This study investigated the synergistic antitumor activity of crizotinib and temozolomide in FIG-ROS1-positive glioblastoma (GB) cells. Ex vivo culture models were used to predict drug response and guide patient selection for clinical trials.

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

Language : English

16.

The effects of ketoconazole and rifampin on the single-dose pharmacokinetics of crizotinib in healthy subjects.

Author: XuHuiping, O'GormanMelissa, TanWeiwei, BregaNicoletta, BelloAkintunde

Crizotinib pharmacokinetics
Well tolerated

Ketoconazole, a strong CYP3A inhibitor, increased crizotinib exposure by 3.2-fold. Rifampin, a strong CYP3A inducer, decreased crizotinib exposure by 82%.

Clinical TrialA clinical trial is a planned study conducted on humans to evaluate the efficacy and safety of pharmaceuticals, medical devices, and treatment methods. It aims to explore the possibilities of new treatments and improve the health of patients.
Controlled Clinical TrialA clinical trial that evaluates the effectiveness of a treatment by comparing a group that receives the intervention with a group that receives a placebo or standard 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

17.

[Therapeutic effects of crizotinib in EML4-ALK-positive patients with non-small-cell lung cancer].

Author: WuXuan, LiJianxiong

Improved PFS in ALK-positive patients
None mentioned

Crizotinib is a more effective treatment for non-small-cell lung cancer (NSCLC) patients with EML4-ALK rearrangement than platinum-based chemotherapy, with an objective response rate of 61.9% and a median response duration of 16 months.

Clinical TrialA clinical trial is a planned study conducted on humans to evaluate the efficacy and safety of pharmaceuticals, medical devices, and treatment methods. It aims to explore the possibilities of new treatments and improve the health 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 : Chinese

18.

Synergistic effects of crizotinib and radiotherapy in experimental EML4-ALK fusion positive lung cancer.

Author: DaiYing, WeiQuanxiang, SchwagerChristian, MoustafaMahmoud, ZhouCheng, LipsonKenneth E, WeichertWilko, DebusJürgen, AbdollahiAmir

Improved NSCLC treatment

Crizotinib, a tyrosine kinase inhibitor, showed a synergistic effect with radiotherapy in ALK-positive non-small cell lung cancer (NSCLC). This combination was more effective in reducing tumor proliferation, microvascular density, and perfusion in an ALK-positive xenograft tumor model compared to radiotherapy alone.

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.

Crizotinib effects on creatinine and non-creatinine-based measures of glomerular filtration rate.

Author: CamidgeD Ross, BrosnanEvelyn M, DeSilvaChamath, KooPhillip J, ChoncholMichel

Crizotinib treatment
Reduced GFR

Crizotinib use may lead to rapid reductions in creatinine-based estimates of the glomerular filtration rate (GFR), but further investigation is needed to determine if this is due to drug-induced changes or the validity of creatinine as a measure of kidney function.

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.
Research Support, N.I.H., ExtramuralResearch funding provided by the NIH to external research institutions and researchers.

Language : English

20.

MET tyrosine kinase inhibitor crizotinib (PF-02341066) shows differential antitumor effects in non-small cell lung cancer according to MET alterations.

Author: TanizakiJunko, OkamotoIsamu, OkamotoKunio, TakezawaKen, KuwataKiyoko, YamaguchiHaruka, NakagawaKazuhiko

Lung cancer treatment

Crizotinib is a tyrosine kinase inhibitor that is being studied for the treatment of lung cancer. This study examined the antitumor action of crizotinib in lung cancer cells that are positive or negative for MET amplification or mutation.

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

Language : English

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