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

Schmidinger, Manuela; Danesi, Romano

doi:10.1634/theoncologist.2017-0335

Cited by 63 publications

(46 citation statements)

References 108 publications

(191 reference statements)

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“…Consequently, it has been suggested that VEGFR and c-Kit inhibition may cause diarrhoea [28]. Management of HFSR, diarrhoea and hypertension is especially important; although they are associated with positive treatment outcomes, they are among the most frequently experienced AEs [2][3][4][5].…”

Section: Association Of Tki Aes With Positive Treatment Outcomesmentioning

confidence: 99%

“…Use of a food diary may be helpful for identifying particular items that exacerbate diarrhoea [51]. Additionally, consumption of bananas, rice, potatoes, apple sauce, toast and probiotics may help to alleviate symptoms [28,53]. It is important to ensure that patients with diarrhoea do not become dehydrated; fluid intake should be increased, and electrolytes monitored and replaced when necessary [36,40,43,45,47].…”

Section: Diarrhoeamentioning

confidence: 99%

“…Patients with fatigue should also be assessed and treated for hypothyroidism, which is commonly associated with TKI treatments [36,37,41,43,45]. Other potential underlying causes of fatigue, such as low testosterone in men, pain, sleep dysfunction, emotional distress, depression and anaemia, should also be considered and treated as required [28,37,45,47,49]. Psychostimulants may be considered for treatment of TKI-related fatigue [45,49,50,53].…”

Section: Fatiguementioning

confidence: 99%

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Management of adverse events associated with tyrosine kinase inhibitors: Improving outcomes for patients with hepatocellular carcinoma

Rimassa

Danesi

Pressiani

et al. 2019

Cancer Treatment Reviews

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175

163

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Hepatocellular carcinoma (HCC) is the most common form of primary liver cancer. Sorafenib, regorafenib, lenvatinib and cabozantinib are tyrosine kinase inhibitors (TKIs) that target, in part, vascular endothelial growth factor receptors, and are approved in various regions of the world for the treatment of advanced HCC. All these agents are associated with a range of adverse events (AEs) that can have a substantial impact on patients' healthrelated quality of life. Fatigue, diarrhoea, hand-foot skin reaction, nausea, vomiting, decreased appetite, hypertension and weight loss are among the most common AEs experienced with these four TKIs. In this review, we discuss strategies for the management of these AEs in patients with advanced HCC, with the aim of maximizing treatment benefits and minimizing the need for TKI treatment discontinuation. We also consider potential TKI-drug interactions and discuss the use of TKIs in patients with liver dysfunction or who have experienced tumour recurrence after liver transplantation. Use of appropriate AE management strategies and avoidance of contraindicated drugs should help patients with advanced HCC to achieve optimal outcomes with TKIs.

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Section: Association Of Tki Aes With Positive Treatment Outcomesmentioning

confidence: 99%

Section: Diarrhoeamentioning

confidence: 99%

Section: Fatiguementioning

confidence: 99%

See 1 more Smart Citation

Management of adverse events associated with tyrosine kinase inhibitors: Improving outcomes for patients with hepatocellular carcinoma

Rimassa

Danesi

Pressiani

et al. 2019

Cancer Treatment Reviews

Self Cite

175

163

View full text Add to dashboard Cite

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“…If patients do not have cardiovascular comorbidity, angiotensin receptor blockers may be the agent of choice as they have been shown to inhibit angiotensin II-mediated growth and migration of cancer cells and angiogenesis. β-Blockers may also have some role in reducing hypertension induced by VEGF pathway inhibitors as they have shown to induce apoptosis in endothelial cells [19]. Our patient was started on amlodipine and metoprolol, which controlled her blood pressure well; ACE inhibitors were not used due to her underlying kidney disease.…”

Section: Discussionmentioning

confidence: 92%

Atypical Posterior Reversible Encephalopathy Syndrome due to Oral Tyrosine Kinase Inhibitor Cabozantinib: First Case Report

Patwari

Bhatlapenumarthi

Pascual³

2020

Case Rep Oncol

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We report here a rare case of atypical posterior reversible encephalopathy syndrome (PRES) due to oral tyrosine kinase inhibitor cabozantinib. No case reports of such have been found in our literature search. The patient, a 70-year-old female with metastatic renal cell cancer on oral tyrosine kinase inhibitor cabozantinib, was brought into the emergency room because of confusion and seizures, found to have elevated blood pressure and atypical MRI findings consistent with PRES due to cabozantinib.

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“…The widespread diffusion of cabozantinib in the treatment algorithm of mRCC raised the question about the clinical effects of its exposure on cardiac function. Of note, the development of hypertension as a result of cabozantinib therapy represents 1 of the most frequently reported side effects, with an incidence of 37% in the METEOR trial (15% of grade 3–4) and of 81% in the CABOSUN study (28% of grade 3–4) . A meta‐analysis of randomized trials of cabozantinib (in different indications) confirmed the increased risk of developing all‐ and high‐grade hypertension, the latter of which had a substantially higher frequency compared to other approved VEGFRs‐TKIs (sorafenib, sunitinib, and pazopanib) .…”

Section: Discussionmentioning

confidence: 95%

Cabozantinib‐related cardiotoxicity: a prospective analysis in a real‐world cohort of metastatic renal cell carcinoma patients

Iacovelli

Ciccarese

Fornarini

et al. 2019

Brit J Clinical Pharma

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Aims: Data regarding the cardiac toxicity of cabozantinib lacks. The aim of our study was to assess the risk of cabozantinib-related cardiotoxicity in mRCC patients. Methods:We performed a multicentre prospective study on mRCC patients treated with cabozantinib between October 2016 and November 2017. Transthoracic echocardiogram and plasma biomarkers assay were assessed at baseline, 3 and 6 months after cabozantinib initiation.Results: The study population included 22 mRCC patients. At baseline, 9.1% had a reduced left ventricular ejection fraction (LVEF), but none had a left ventricular systolic dysfunction. Patients with baseline reduced LVEF did not show further significant LVEF modification after 3 months. After 6 months, only 1 had an LVEF decline >10% compared to baseline, resulting in LV systolic dysfunction. At baseline, 64.7% and 27.3% of patients had elevated precursor brain natriuretic peptide (proBNP) and high-sensitivity troponin I (hsTnI), respectively. Among patients with basal normal proBNP and hsTnI, none had elevated values at 3 and 6 months. No correlation was found between basal elevated proBNP and basal reduced LVEF (P = .29), and between elevated proBNP and reduced LVEF after 6 months (P = .37). Similarly, we found no correlations between elevated hsTnI and reduced LVEF or elevated proBNP at baseline (P = .47; P = .38), at 3 (P = .059; P = .45) and after 6 months (P = .72;Conclusions: This prospective study revealed a modest risk of developing left ventricular systolic dysfunction related to cabozantinib. A lack of correlation between elevated cardiac biomarkers and reduced LVEF at different time-points was detected.Assessments of the cardiac function should be reserved at the occurrence of clinical symptoms. KEYWORDS cabozantinib, cardiotoxicity, high-sensitivity troponin I, metastatic renal cell carcinoma, precursor brain natriuretic peptide Small-molecule tyrosine kinase inhibitors (TKIs) targeting the vascular endothelial growth factor receptors (VEGFRs)-sunitinib, pazopanib, sorafenib, axitinib and cabozantinib-have revolutionized the treatment algorithm of patients with metastatic renal cell carcinoma (mRCC), by improving clinical outcomes in randomized phase III trials. 1 In the last 10 years, as a result of the routine use of VEGFRs-TKIs in clinical practice, the median overall survival (OS) of mRCC patients reached 30 months, with variations depending on the patients prognostic risk group. Cabozantinib (a MET, VEGFRs and AXL TKI) represents the only one that demonstrated an OS-besides progression-free survival (PFS) and objective response rate-advantage compared with everolimus in pretreated mRCC patients in the phase III METEOR study. 2 Moreover, a phase II study (CABOSUN trial) tested the activity of cabozantinib in first-line in previously untreated mRCC patients of intermediate-or poor-risk according to the International Metastatic Renal Cell Carcinoma Database Consortium risk model. 3 Albeit with concerns regarding the relatively poor efficacy of the control arm in which suniti...

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

Cited by 63 publications

References 108 publications

Management of adverse events associated with tyrosine kinase inhibitors: Improving outcomes for patients with hepatocellular carcinoma

Management of adverse events associated with tyrosine kinase inhibitors: Improving outcomes for patients with hepatocellular carcinoma

Atypical Posterior Reversible Encephalopathy Syndrome due to Oral Tyrosine Kinase Inhibitor Cabozantinib: First Case Report

Cabozantinib‐related cardiotoxicity: a prospective analysis in a real‐world cohort of metastatic renal cell carcinoma patients

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