Effects of pazopanib: A Synthesis of Findings from 18 Studies

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Original Abstract of the Article

Major Research Findings

Pazopanib is a multi-targeted tyrosine kinase inhibitor that has been approved for the treatment of metastatic renal cell carcinoma and advanced soft tissue sarcoma. 2 、 5 、 1 Similar to other tyrosine kinase inhibitors, pazopanib can prolong cardiac repolarization and cause proarrhythmic effects. 2 Pazopanib can cause hypertension, and the effects may last for a long time after stopping the drug. 17 Pazopanib has shown potential benefits in treating various cancers by inhibiting angiogenesis, the formation of new blood vessels that supply tumors with oxygen and nutrients. 4 、 12 、 1 Pazopanib was found to be effective in treating metastatic tumors in the lungs. In a case report, pazopanib showed a paradoxical antitumor effect in a cutaneous angiosarcoma patient. Pazopanib is a potential treatment option for medullary thyroid cancer, as it may increase progression-free survival and prolong lifetime. 5 In preclinical models, pazopanib has shown promise in treating renal cell carcinoma by inhibiting angiogenesis and tumor growth. 8 Pazopanib could be effective in treating prostate leiomyosarcoma. Pazopanib has shown effectiveness in treating soft tissue sarcoma. 11 Pazopanib is a potential therapeutic agent for hepatocellular carcinoma. 13 Pazopanib and lapatinib, when used together, may synergistically induce apoptosis in cancer cells. 18 Pazopanib can lead to oral side effects. 7 Pazopanib may impact the pharmacokinetics of doxorubicin. 14 Pazopanib can cause liver toxicity, but the administration of taxifolin can prevent it. 16 Pazopanib can improve cognitive function in an Alzheimer’s disease rat model, potentially by suppressing the RIPK1/RIPK3/MLKL necroptosis signaling pathway. 15 Pazopanib is found to be well-tolerated compared to sorafenib and sunitinib in patients with soft tissue sarcoma. 9 The effect of pazopanib might vary based on the polymorphism in the BIM gene. Pazopanib shows good tolerability and may lead to long-term survival in treating metastatic renal cell carcinoma. 10 Pazopanib pharmacokinetics might be affected when it is used with ketoconazole or esomeprazole. 6 Pazopanib is effective in reducing the growth of endometriotic implants. 3

Benefits and Risks

Benefit Summary

Pazopanib has shown potential benefits in treating various cancers, including metastatic renal cell carcinoma, advanced soft tissue sarcoma, and medullary thyroid cancer. 5 、 1 、 10 It has the ability to inhibit angiogenesis, thus potentially slowing down tumor growth. 4 、 12 、 1 Pazopanib may be well-tolerated compared to other tyrosine kinase inhibitors and lead to long-term survival. 9 、、 10 Pazopanib can work synergistically with other anticancer drugs, leading to enhanced therapeutic outcomes. 18 Pazopanib can improve cognitive function in an Alzheimer’s disease rat model, potentially by suppressing the RIPK1/RIPK3/MLKL necroptosis signaling pathway. 15

Risk Summary

Pazopanib comes with potential risks like QT interval prolongation, hypertension, liver toxicity, and oral side effects. 2 、 17 、 7 、 16 It may also affect the pharmacokinetics of doxorubicin. 14 Furthermore, its pharmacokinetics can be impacted when used with ketoconazole or esomeprazole. 6

Comparison of Studies

Commonalities

Many studies consistently show that pazopanib can effectively suppress tumor growth by inhibiting angiogenesis. 4 、 12 、 1 、 8 Moreover, numerous studies indicate that pazopanib demonstrates therapeutic benefits in various types of cancers. 5 、、、 11 、 13

Differences

The findings regarding the side effects of pazopanib vary across studies. 2 、 17 、 7 、 16 The effectiveness of pazopanib can also differ based on the type of cancer and individual patient characteristics.

Consistency and Contradictions

Numerous studies have demonstrated that pazopanib is effective in treating various cancers. 1 However, it’s important to acknowledge that pazopanib carries risks like QT interval prolongation, hypertension, and liver toxicity. 2 、 17 、 16 Since the side effects can differ between patients, it’s crucial to discuss them with your doctor. 9 、 Pazopanib pharmacokinetics can be influenced by co-administration with certain drugs such as ketoconazole or esomeprazole. 6 Consult your doctor before taking pazopanib if you are taking any other medications.

Practical Applications and Considerations

While pazopanib can be a valuable treatment option for certain cancers, it’s essential to be aware of the associated risks. 2 、 17 、 16 Always follow your doctor’s instructions and get regular blood tests while taking pazopanib. 9 Co-administration with other medications can alter the effectiveness and side effects of pazopanib, so inform your doctor about any medications you are currently taking before starting pazopanib. 6 Pazopanib should not be used by pregnant or breastfeeding women.

Limitations of Current Research

Research on pazopanib is still ongoing, and more research is needed, especially on how pazopanib affects different types of cancer and how to prevent or reduce its side effects. 、 3 、 9

Future Research Directions

Further research is needed to explore ways to minimize the side effects of pazopanib. 9 Research is also necessary to enhance the effectiveness of pazopanib. 9 Pazopanib holds promise for treating various cancers, so more research is needed to investigate its effectiveness across different cancer types. 1 Since side effects can vary between individuals, additional research is needed to predict and manage these effects. 9

Conclusion

Pazopanib could be an effective treatment option for cancers like metastatic renal cell carcinoma and advanced soft tissue sarcoma. 5 However, it is crucial to understand that pazopanib carries risks, including QT interval prolongation, hypertension, and liver toxicity. 2 、 17 、 16 Consult your doctor regularly and get regular blood tests to monitor your health while taking pazopanib. 9 Always inform your doctor about all medications you are currently taking before starting pazopanib, as interactions with other drugs can affect its effectiveness and side effects. 6 Pazopanib is contraindicated during pregnancy and breastfeeding.

Literature analysis of 18 papers
Positive Content
17
Neutral Content
0
Negative Content
1
Article Type
0
0
1
2
17
1.

The role of pazopanib on tumour angiogenesis and in the management of cancers: A review.

Author: ChellappanDinesh Kumar, ChellianJestin, NgZhao Yin, SimYan Jinn, ThengChiu Wei, LingJoyce, WongMei, FooJia Hui, YangGoh Jun, HangLi Yu, NathanSaranyah, SinghYogendra, GuptaGaurav

Anti-angiogenic effect
Cancer treatment

Pazopanib is a chemotherapy drug with anti-angiogenic properties, which can inhibit the growth of blood vessels that supply tumors. This review analyzed 352 studies about pazopanib and its anti-angiogenic effects in various cancers. Pazopanib showed anti-angiogenic effects in several cancers, such as renal cell carcinoma, solid tumors, and soft tissue sarcoma.

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.
Systematic ReviewA review that systematically collects, evaluates, and integrates relevant research to answer a specific research question.

Language : English

3.

Effects of Pazopanib, Sunitinib, and Sorafenib, Anti-VEGF Agents, on the Growth of Experimental Endometriosis in Rats.

Author: YildizCaglar, KacanTurgut, AkkarOzlem Bozoklu, KarakusSavas, KacanSelen Baloglu, OzerHatice, CetinAli

Reduced endometriosis

Pazopanib, sunitinib, and sorafenib are drugs that can be used to treat endometriosis. This study found that pazopanib and sunitinib were more effective than sorafenib in reducing the growth of endometriotic implants in rats, but none of the drugs affected ovarian reserve.

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.

Anti-angiogenic effects of the receptor tyrosine kinase inhibitor, pazopanib, on choroidal neovascularization in rats.

Author: YafaiYousef, YangXiu Mei, NiemeyerMarc, NishiwakiAkiko, LangeJohannes, WiedemannPeter, KingAndrew G, YasukawaTsutomu, EichlerWolfram

Angiogenesis inhibition
CNV treatment

Pazopanib, a drug that targets multiple receptor tyrosine kinases, is a promising inhibitor of angiogenesis. In a study of rats with experimentally induced choroidal neovascularization (CNV), topical pazopanib treatment significantly decreased leakage and thickness of CNV lesions.

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.

Pazopanib, Cabozantinib, and Vandetanib in the Treatment of Progressive Medullary Thyroid Cancer with a Special Focus on the Adverse Effects on Hypertension.

Author: MillingRikke Vilsbøll, GrimmDaniela, KrügerMarcus, GrosseJirka, KoppSascha, BauerJohann, InfangerManfred, WehlandMarkus

Increased PFS
MTC treatment
Prolonged lifetime
Cardiovascular disease
Hypertension

Tyrosine kinase inhibitors (TKIs) are effective in treating medullary thyroid cancer (MTC) and have shown promising results in increasing progression-free survival, but they are associated with hypertension, which can worsen patient well-being.

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.

Effects of ketoconazole and esomeprazole on the pharmacokinetics of pazopanib in patients with solid tumors.

Author: TanAntoinette R, GibbonDarlene G, SteinMark N, LindquistDiana, EdenfieldJeffery W, MartinJulie C, GregoryCharles, SuttleA Benjamin, TadaHiroomi, BotbylJeffrey, StephensonJoseph J

Drug interaction

This study examines the effect of ketoconazole and esomeprazole on the pharmacokinetics and safety of pazopanib, a drug primarily metabolized by CYP3A4. The findings suggest potential interactions between these drugs and pazopanib.

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.
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

7.

Oral Side Effects in Patients with Metastatic Renal Cell Carcinoma Receiving the Antiangiogenic Agent Pazopanib-Report of Three Cases.

Author: PapadopoulouErofili, VardasEmmanouil, TzivelekaStyliani, GeorgakiMaria, KouriMaria, KatoumasKonstantinos, PiperiEvangelia, NikitakisNikolaos G

Tumor growth inhibition
Bleeding
Jaw osteonecrosis

This study reports three cases of patients with metastatic renal cell carcinoma (mRCC) who developed adverse oral events related to pazopanib, a potent multi-kinase inhibitor. The reported adverse events include gingival bleeding and medication-related osteonecrosis of the jaw (MRONJ). The cases emphasize the importance of informing healthcare professionals about the potential oral side effects of pazopanib in patients with mRCC.

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

10.

Good tolerability, long-term survival and easy management of side effects in a patient with metastatic renal cell carcinoma treated with pazopanib.

Author: FrascaroliMara, Di CesarePamela

Efficacy of pazopanib
Good tolerability
Elevated transaminase levels

This case report describes a patient with metastatic renal cell carcinoma who was successfully treated with pazopanib, a tyrosine kinase inhibitor. The patient experienced few side effects and maintained a good quality of life during 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.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.

Language : English

11.

Establishment of a novel clear cell sarcoma cell line (Hewga-CCS), and investigation of the antitumor effects of pazopanib on Hewga-CCS.

Author: OutaniHidetatsu, TanakaTakaaki, WakamatsuToru, ImuraYoshinori, HamadaKenichiro, ArakiNobuhito, ItohKazuyuki, YoshikawaHideki, NakaNorifumi

CCS research

A novel CCS cell line called Hewga-CCS was established and used to develop an orthotopic tumor xenograft model for comprehensive research in CCS.

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

12.

The B-Raf status of tumor cells may be a significant determinant of both antitumor and anti-angiogenic effects of pazopanib in xenograft tumor models.

Author: GrilBrunilde, PalmieriDiane, QianYong, AnwarTalha, IlevaLilia, BernardoMarcelino, ChoykePeter, LiewehrDavid J, SteinbergSeth M, SteegPatricia S

Anti-angiogenesis
Tumor growth inhibition

Pazopanib, a vascular endothelial growth factor receptor inhibitor, was found to be effective against tumors expressing certain B-Raf genotypes, particularly those with exon 11 mutations.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, N.I.H., IntramuralFunding provided by the NIH for research projects within the NIH.
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

13.

Antiangiogenic effects of pazopanib in xenograft hepatocellular carcinoma models: evaluation by quantitative contrast-enhanced ultrasonography.

Author: ZhuXiao-Dong, ZhangJu-Bo, FanPei-Li, XiongYu-Quan, ZhuangPeng-Yuan, ZhangWei, XuHua-Xiang, GaoDong-Mei, KongLing-Qun, WangLu, WuWei-Zhong, TangZhao-You, DingHong, SunHui-Chuan

Antiangiogenic effects
Tumor growth inhibition

Pazopanib, a pan-vascular endothelial growth factor receptor inhibitor, showed anti-angiogenic effects on human hepatocellular carcinoma cell lines and effectively inhibited tumor growth in xenograft nude mice models.

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

14.

The effects of pazopanib on doxorubicin pharmacokinetics in children and adults with non-rhabdomyosarcoma soft tissue sarcoma: a report from Children's Oncology Group and NRG Oncology study ARST1321.

Author: GartrellJ, PanettaJ C, BakerS D, ChenY L, HawkinsD S, OstrengaA, ScharschmidtT J, SpuntS L, WangD, WeissA R

Pathological response

This exploratory aim study assessed the effect of pazopanib on doxorubicin pharmacokinetic (PK) parameters in patients receiving chemotherapy and pazopanib for non-rhabdomyosarcoma soft tissue sarcomas.

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

16.

Protective effects of taxifolin on pazopanib-induced liver toxicity: an experimental rat model.

Author: AkagunduzBaran, OzerMuhammet, OzcıcekFatih, KaraAli Veysel, LacınSahin, ÖzkaracaMustafa, ÇobanAbdulkadir, SuleymanBahadır, MammadovRenad, SuleymanHalis

Hepatotoxicity prevention

Taxifolin, a flavonoid, was effective in preventing pazopanib-induced hepatotoxicity in rats.

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

Language : English

17.

Long-term cardiovascular effects of vandetanib and pazopanib in normotensive rats.

Author: CooperSamantha L, CarterJoanne J, MarchJulie, WoolardJeanette

PDGF inhibition
VEGF inhibition
Cardiovascular risk
Hypertension

This study investigated the longer-term cardiovascular implications of vandetanib and pazopanib, multi-targeted inhibitors of VEGF and PDGF receptor tyrosine kinases, in conscious rats. Both drugs caused sustained increases in blood pressure, suggesting that their cardiovascular effects persist even after cessation of 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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