Side Effects of cabozantinib: A Synthesis of Findings from 26 Studies

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Original Abstract of the Article

Key Research Findings

Cabozantinib is a multi-targeted kinase inhibitor used for the treatment of several cancers. By targeting multiple signaling pathways, MKIs have become cornerstones of the oncologic treatment. Although their use leads to important results in terms of survival, treatment with MKIs can determine important side effects the clinician must be aware of. Among those, arterial hypertension, mucositis and skin lesions are universally reported, while data about metabolic alterations are scarce. In our review, we focused on glucose and lipid alterations in MKI-treated patients. 26

A study evaluating the correlation between the incidence of adverse events and progression-free survival (PFS) in patients treated with cabozantinib for metastatic renal cell carcinoma (mRCC) found that hypertension, hypothyroidism, and hand-foot syndrome were the most frequent, occurring in about two-thirds of patients. Multiple adverse events were also common, with hypertension, hypothyroidism, diarrhea, and liver toxicity significantly associated with longer PFS values. Patients with three or more side effects had significantly longer PFS than those with two or fewer. 5

There have been reports of bronchial perforation occurring when using a combination of cabozantinib and nivolumab for a tumor with bronchial invasion, with the tumor shrinking. In this case, the patient developed fever and cough and was hospitalized for right lobar pneumonia. Long-term antibiotics were given for bronchial fistula with destruction of the bronchial wall and secondary lung abscess. 18

Cabozantinib is approved for the treatment of advanced renal cell carcinoma. Cabozantinib is a multikinase inhibitor that targets VEGF receptor (VEGFR) 2, mesenchymal-epithelial transition receptor, and "anexelekto" receptor tyrosine kinase. Like other VEGFR inhibitors, cabozantinib can cause toxicity that may affect the patient's quality of life. The most frequent adverse events (AEs) are diarrhea, fatigue, hypertension, hand-foot syndrome, weight loss, nausea, and stomatitis. Adequate interventions can ensure optimum adherence and maximize patient outcomes. 21

Reasons for Side Effects

Cabozantinib inhibits multiple receptor tyrosine kinases, including vascular endothelial growth factor receptor (VEGFR) 2, mesenchymal-epithelial transition factor (MET), and AXL. VEGFR is involved in angiogenesis, and inhibiting VEGFR is thought to suppress tumor growth and metastasis. However, VEGFR inhibitors can affect the blood vessels of normal tissues by inhibiting angiogenesis, leading to side effects such as hypertension and hand-foot syndrome. 2

Common Side Effects

Hypertension

This is one of the major side effects of cabozantinib. 2

Hand-foot Syndrome

This is one of the potential side effects that can occur during cabozantinib treatment. 21

Diarrhea

This is one of the potential side effects that can occur during cabozantinib treatment. Crofelemer may help manage diarrhea caused by cabozantinib treatment. 23

Fatigue

This is one of the potential side effects that can occur during cabozantinib treatment. 21

Weight Loss

This is one of the potential side effects that can occur during cabozantinib treatment. 21

Nausea

This is one of the potential side effects that can occur during cabozantinib treatment. 21

Stomatitis

This is one of the potential side effects that can occur during cabozantinib treatment. 21

Hypothyroidism

This is one of the potential side effects that can occur during cabozantinib treatment. 5

Bronchial Perforation

This is one of the potential side effects that can occur during combination therapy with cabozantinib and nivolumab. 18

Countermeasures for Side Effects

Hypertension

If hypertension occurs during cabozantinib treatment, appropriate treatment, such as administration of antihypertensive drugs, is needed. 1

Diarrhea

Crofelemer may help manage diarrhea caused by cabozantinib treatment. 23

Hand-foot Syndrome

If hand-foot syndrome occurs, appropriate measures, such as reducing the dosage of cabozantinib, are needed. 21

Comparison between Studies

Commonalities among Studies

Multiple studies have shown that cabozantinib is effective in treating metastatic renal cell carcinoma. However, cabozantinib can cause side effects such as hypertension, hand-foot syndrome, and diarrhea. 5 21

Differences among Studies

The incidence and severity of side effects from cabozantinib may vary between studies. This is thought to be influenced by differences in the patient population and study design. 5 21

Cautions Regarding Application to Real Life

Cabozantinib has been shown to be effective in treating metastatic renal cell carcinoma, but it can cause side effects such as hypertension, hand-foot syndrome, and diarrhea. To minimize side effects and maximize therapeutic efficacy, it is essential to follow the doctor's instructions carefully and undergo regular checkups. 5 21

Limitations of Current Research

Research on the side effects of cabozantinib is still limited. In particular, data on metabolic changes is lacking. Further research is needed on methods to predict and prevent the occurrence of side effects. Additionally, research on the interaction of cabozantinib with other drugs is required. 26

Future Research Directions

It is crucial to investigate the side effects of cabozantinib in more detail and elucidate their mechanisms of occurrence. Further research is needed on methods to predict and prevent the occurrence of side effects. Additionally, investigation into the interaction of cabozantinib with other drugs is necessary. 26

Conclusion

Cabozantinib is a multi-targeted kinase inhibitor that is effective in treating metastatic renal cell carcinoma. However, cabozantinib can cause side effects such as hypertension, hand-foot syndrome, and diarrhea. When receiving cabozantinib treatment, it is important to understand the risks and benefits of the side effects and to consult with your doctor. 5 21

Literature analysis of 26 papers
Positive Content
22
Neutral Content
2
Negative Content
2
Article Type
1
3
5
13
24
1.

[Side effect management of tyrosine kinase inhibitors in urology : Hypertension].

Author: SikicD, MeidenbauerN, LiebV, KeckB

Hypertension

This review focuses on hypertension, a significant side effect of tyrosine kinase inhibitors used in metastatic renal cell carcinoma treatment. The authors provide an overview of hypertension classification and treatment strategies to improve treatment efficacy and patient compliance.

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 : German

2.

Incidence and risk of hypertension associated with cabozantinib in cancer patients: a systematic review and meta-analysis.

Author: ZhangXi, ShaoYongjie, WangKunjie

Cancer treatment
Hypertension

Cabozantinib, a tyrosine kinase inhibitor, is associated with a high incidence of hypertension in cancer patients.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Meta-AnalysisA statistical technique that integrates the results of multiple studies to draw more general conclusions about a particular issue.
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

6.

Fulminant Type 1 Diabetes Mellitus Caused by Long-Term Nivolumab Administration Followed by Nivolumab plus Cabozantinib Combination.

Author: HommaTakamasa, YoshidaNorio, TanakaKuniaki, IsemuraMasaya, ToriiShota, KinoshitaTeruhisa, EsakiHideki, SakakibaraTakashi, TakimotoNorio

Cancer treatment
Fulminant type 1 diabetes
Glycemic control

A patient who received long-term nivolumab, an immune checkpoint inhibitor, followed by combination therapy with nivolumab and cabozantinib, a multikinase inhibitor, developed fulminant type 1 diabetes. This case highlights the potential risk of fulminant diabetes with combination therapy, emphasizing the need for careful glycemic control in such patients.

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.

First Line Sorafenib Treatment for Metastatic Medullary Thyroid Cancer: Efficacy and Safety Analysis.

Author: KocsisJudit, SzekaneczÉva, BassamAli, UhlyarikAndrea, PápaiZsuzsanna, RubovszkyGábor, MezősiEmese, RuczKároly, GaraiIldikó, NagyEndre, UrayIván, HorváthZsolt

MTC treatment

Medullary thyroid cancer (MTC) is a rare disease with poor prognosis for advanced and metastatic disease. This study investigated the efficacy and safety of sorafenib, a tyrosine kinase inhibitor, in patients with metastatic MTC.

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

Language : English

8.

Cabozantinib in hepatocellular carcinoma: results of a phase 2 placebo-controlled randomized discontinuation study.

Author: KelleyR K, VerslypeC, CohnA L, YangT-S, SuW-C, BurrisH, BraitehF, VogelzangN, SpiraA, FosterP, LeeY, Van CutsemE

AFP reduction
HCC treatment
Tumor regression
Diarrhea
Hand-foot syndrome
Thrombocytopenia

This phase 2 randomized discontinuation trial assessed the efficacy and safety of cabozantinib in patients with hepatocellular carcinoma (HCC). The study found that cabozantinib had clinical activity in HCC patients, including objective tumor responses, disease stabilization, and reductions in alpha-fetoprotein (AFP). The most common grade 3/4 adverse events were diarrhea, hand-foot syndrome, and thrombocytopenia, which were managed with dose reductions. This suggests that cabozantinib may be a promising treatment option for HCC, but further research is needed to confirm its efficacy and long-term safety.

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.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.

Language : English

9.

Cabozantinib in the treatment of advanced renal cell carcinoma in adults following prior vascular endothelial growth factor targeted therapy: clinical trial evidence and experience.

Author: OsantoSusanne, van der HulleTom

Higher response rate
Improved survival
Side effects

Cabozantinib, a multitargeted tyrosine kinase inhibitor, is an effective second-line treatment option for patients with advanced renal cell carcinoma.

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.

Effects of tyrosine kinase inhibition on bone metabolism: untargeted consequences of targeted therapies.

Author: AlemánJosé O, FarookiAzeez, GirotraMonica

Bone resorption inhibition
Cancer treatment
Bone health effects

Tyrosine kinase inhibitors (TKIs) have redefined oncologic treatment with tolerable side effect profiles compared with cytotoxic agents. This review examines the effects of TKIs on bone mineral metabolism, focusing on the off-target effects that contribute to changes in bone cell maturation, activity, and bone mass.

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

12.

Treatment of advanced thyroid cancer with targeted therapies: ten years of experience.

Author: ViolaDavid, ValerioLaura, MolinaroEleonora, AgateLaura, BotticiValeria, BiaginiAgnese, LorussoLoredana, CappagliVirginia, PieruzziLetizia, GianiCarlotta, SabiniElena, PassannatiPaolo, PuleoLuciana, MatroneAntonio, Pontillo-ContilloBenedetta, BattagliaValentina, MazzeoSalvatore, VittiPaolo, EliseiRossella

Thyroid cancer treatment

Tyrosine kinase inhibitors (TKIs) are showing promise in the treatment of advanced cases of thyroid cancer. TKIs such as sorafenib, lenvatinib, vandetanib, and cabozantinib have been approved for use in clinical practice for different types of thyroid cancer.

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

13.

Exposure-toxicity relationship of cabozantinib in patients with renal cell cancer and salivary gland cancer.

Author: KrensStefanie D, van BoxtelWim, UijenMaike J M, JansmanFrank G A, DesarIngrid M E, MulderSasja F, van HerpenCarla M L, van ErpNielka P

RCC treatment
SGC treatment
Toxicity

This study explored the cabozantinib exposure in patients with different tumor types, finding that salivary gland carcinoma patients had significantly higher cabozantinib exposure at the starting dose compared to renal cell carcinoma patients.

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

Language : English

15.

[Collecting duct carcinoma].

Author: SondermannMarcus, GüntherMarlis, EnzmannThomas

Survival prolongation
Targeted therapy
Short survival
Side effects

Collecting duct carcinoma is a rare and aggressive type of kidney cancer. This article discusses the current treatment options for this disease, including surgery, chemotherapy, immunotherapy, and targeted therapy.

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 : German

16.

A systematical comparison of anti-angiogenesis and anti-cancer efficacy of ramucirumab, apatinib, regorafenib and cabozantinib in zebrafish model.

Author: WuJia-Qi, FanRuo-Yue, ZhangShi-Ru, LiChong-Yong, ShenLi-Zong, WeiPin, HeZhi-Heng, HeMing-Fang

Anti-angiogenic therapy
Safety

This study systemically compared the anti-angiogenesis, anti-cancer efficacy, and safety of four anti-angiogenic drugs (ramucirumab, apatinib, regorafenib, and cabozantinib) for the treatment of gastric 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

17.

Molecular targets of tyrosine kinase inhibitors in thyroid cancer.

Author: FallahiPoupak, FerrariSilvia Martina, GaldieroMaria Rosaria, VarricchiGilda, EliaGiusy, RagusaFrancesca, PaparoSabrina Rosaria, BenvengaSalvatore, AntonelliAlessandro

Cancer treatment
DTC treatment
Drug resistance
Side effects

Thyroid cancer (TC) is the eighth most frequently diagnosed cancer worldwide with a rising incidence in the past 20 years. This review discusses the use of tyrosine kinase inhibitors (TKIs) as new treatments for DTC, MTC and anaplastic TC (ATC).

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

18.

Simultaneous tumor shrinkage and bronchial perforation induced by nivolumab plus cabozantinib combination therapy in a patient with collecting duct carcinoma.

Author: OkumuraHiroki, MuraseKyoko, OkaSuguru, KizawaRika, YamaguchiTakeshi, TanabeYuko, SuyamaKoichi, SakaguchiKazushige, UrakamiShinji, MiuraYuji

Nivolumab + cabozantinib perforation

This case report describes a patient who developed bronchial perforation following tumor shrinkage after treatment with nivolumab plus cabozantinib. This highlights the importance of considering bronchial perforation as a potential side effect of vascular endothelial growth factor receptor tyrosine kinase inhibitors, especially in patients with bronchial invasion.

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

19.

Therapy of endocrine disease: response and toxicity of small-molecule tyrosine kinase inhibitors in patients with thyroid carcinoma: a systematic review and meta-analysis.

Author: Klein HesselinkE N, SteenvoordenD, KapiteijnE, CorssmitE P, van der Horst-SchriversA N A, LefrandtJ D, LinksT P, DekkersO M

TC treatment
Toxicity

This systematic review and meta-analysis compared the efficacy and toxicity of tyrosine kinase inhibitors (TKIs) in patients with differentiated thyroid carcinoma (DTC) and medullary thyroid carcinoma (MTC). The aim was to summarize the response and toxicity profiles of TKIs in these specific subtypes of thyroid cancer.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Meta-AnalysisA statistical technique that integrates the results of multiple studies to draw more general conclusions about a particular issue.
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.
Systematic ReviewA review that systematically collects, evaluates, and integrates relevant research to answer a specific research question.

Language : English

20.

Recent advances in the molecular targeted drugs for prostate cancer.

Author: GaoPudong, LiTao, ZhangKuiyuan, LuoGuangheng

Prostate cancer treatment
Adverse drug reactions
Hormone resistance

This study explores the challenges of treating advanced prostate cancer (PCa) in China, including refractory hormone resistance and adverse drug reactions.

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.

Language : English

21.

Management of Adverse Events Associated with Cabozantinib Therapy in Renal Cell Carcinoma.

Author: SchmidingerManuela, DanesiRomano

Improved PFS
Improved survival
Diarrhea
Fatigue
Hand-foot syndrome
Hypertension
Nausea
Stomatitis
Weight loss

Cabozantinib is approved for treating advanced renal cell carcinoma (RCC) after treatment with vascular endothelial growth factor (VEGF)-targeted therapy. This study summarizes the safety profile of cabozantinib in RCC patients and offers guidance for managing adverse events such as diarrhea, fatigue, hypertension, hand-foot syndrome, weight loss, nausea, and stomatitis.

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

22.

Regorafenib in hepatocellular carcinoma: latest evidence and clinical implications.

Author: PersoneniNicola, PressianiTiziana, SantoroArmando, RimassaLorenza

HCC treatment

This review discusses the recent therapeutic advances in the treatment of hepatocellular carcinoma (HCC), highlighting the emergence of multikinase inhibitors and immunotherapy as promising treatment options. The authors emphasize the potential of regorafenib and cabozantinib in second-line settings and the promising signals from nivolumab in immunotherapy.

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

23.

Improved Control of Tyrosine Kinase Inhibitor-Induced Diarrhea with a Novel Chloride Channel Modulator: A Case Report.

Author: GreeneClaire, BarlesiBrigid, Tarroza-DavidSigrid, FriedlanderTerence

Diarrhea control

This case report describes the successful management of cabozantinib-induced diarrhea using crofelemer in a patient with metastatic papillary renal cell carcinoma.

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

Language : English

24.

The dilemma of metastatic medullary thyroid carcinoma: when to start systemic treatment.

Author: SianoMarco, AlfieriSalvatore, GranataRoberta, CalaresoGiuseppina, OrlandiEster, BergaminiCristiana, LocatiLaura Deborah

MTC treatment
MTC progression
TKI toxicity

This case report presents a patient with recurrent/metastatic medullary thyroid carcinoma (MTC) exhibiting a discordant disease behavior, with spontaneous regression in some areas while bone metastases progressed. This case highlights the challenges in deciding when and which tyrosine kinase inhibitor (TKI) to initiate in MTC patients.

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

25.

Pigmentary changes in patients treated with targeted anticancer agents: A systematic review and meta-analysis.

Author: DaiJulia, BelumViswanath R, WuShenhong, SibaudVincent, LacoutureMario E

Pigmentary changes

Targeted cancer therapies are associated with a significant risk of developing pigmentary changes in the skin and hair. A systematic review and meta-analysis of 36 clinical trials involving 8052 patients found that the incidence of pigmentary changes was 17.7% for skin and 21.5% for hair. The relative risks were 93.7 for skin and 20.1 for hair. The most common offending agents were epidermal growth factor receptor and breakpoint cluster region-abelson inhibitors.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Meta-AnalysisA statistical technique that integrates the results of multiple studies to draw more general conclusions about a particular issue.
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

26.

Metabolic adverse events of multitarget kinase inhibitors: a systematic review.

Author: AcitelliElisa, MaiorcaCarlo, GraniGiorgio, MaranghiMarianna

Cancer treatment
Arterial hypertension
Metabolic alterations
Mucositis
Skin lesions

This review focuses on glucose and lipid alterations in patients treated with multitargeted kinase inhibitors (MKIs), highlighting the importance of understanding these metabolic alterations as potential side effects of MKI therapy.

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.

Language : English

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