Axitinib for the Management of Metastatic Renal Cell Carcinoma

Escudier, Bernard; Gore, Martin

doi:10.1007/bf03259801

Cited by 16 publications

(21 citation statements)

References 53 publications

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“…For example, pancreatic cancer studies have reported a longer survival for patients with sunitinib-or bevacizumab-related hypertension. [45][46][47] In renal carcinoma, similar outcomes have been observed with axitinib treatment. 46 Others were unable to confirm a prognostic value of elevated AP for Arterial hypertension modifies glioma growth A Letourneur et al GBM, but the investigation had a small cohort including a few patients with treatment-induced hypertension.…”

Section: Discussionsupporting

confidence: 54%

“…[45][46][47] In renal carcinoma, similar outcomes have been observed with axitinib treatment. 46 Others were unable to confirm a prognostic value of elevated AP for Arterial hypertension modifies glioma growth A Letourneur et al GBM, but the investigation had a small cohort including a few patients with treatment-induced hypertension. 48 Conversely, Lombardi et al 49 found hypertension to be an effective biomarker in patients suffering from recurrent GBM treated with antiangiogenic agents.…”

Section: Discussionsupporting

confidence: 54%

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Chronic arterial hypertension impedes glioma growth: a multiparametric MRI study in the rat

et al. 2015

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Glioblastoma is the most aggressive brain tumor and is almost always fatal. These tumors are highly vascularized and angiogenesis is one of the pre-eminent mechanisms underlying their growth. Chronic arterial hypertension (CAH) is a common and worldwide pathology that markedlly alters the structure and function of the vasculature. Yet, essential hypertension is associated in the brain with potential locally impaired vasoreactivity, disturbed perfusion supply and hypoxia phenomena. Even though CAH is a global burden and has an important impact on brain function, nothing is known about the way this frequent pathology would interact with the evolution of glioma. We sought to determine if arterial hypertension influences gliobastoma growth. In the present study, rat glioma C6 tumor cells were implanted in the caudate-putamen of spontaneously hypertensive rats (SHR) or their normotensive controls, the Wistar-Kyoto (WKY) rats. The evolution of the tumor was sequentially analyzed by multiparametric magnetic resonance imaging and the inflammatory response was examined by histochemistry. We found that CAH significantly attenuates the growth of the tumor as, at 21 days, the volume of the tumor was 85.4±34.7 and 126.1±28.8 mm(3), respectively, in hypertensive and normotensive rats (P<0.02). Moreover, cerebral blood volume and cerebral blood flow were greater in the tumors of hypertensive rats (P<0.05). The lesser growth of the tumor observed in normotensive animals was not due to an enhanced rejection of the tumor cells in WKY rats, the inflammatory response being similar in both groups. For the first time, these results show that CAH impedes the growth of glioblastoma and illustrate the need to further study the impact of hypertension on the evolution of brain tumors.

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Section: Discussionsupporting

confidence: 54%

Section: Discussionsupporting

confidence: 54%

Chronic arterial hypertension impedes glioma growth: a multiparametric MRI study in the rat

et al. 2015

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“…In that study, the incidence of all grade and high grade hypertension with axitinib was also higher than that with sorafenib (all grade 40% vs. 29%; high grade 16% vs. 11%).The reasons for the higher incidence of hypertension with axitinib as compared with other VEGFR-TKIs might be a difference in spectrum and specificity of target receptors. Axitinib is structurally designed to bind to VEGF receptors with high potency and specificity [2,33]. The in vitro halfmaximal inhibitory concentrations (IC50) of axitinib against VEGFR 1-3 were 0.1-0.3 nmol l -1 [2].…”

Section: Figurementioning

confidence: 99%

“…The in vitro halfmaximal inhibitory concentrations (IC50) of axitinib against VEGFR 1-3 were 0.1-0.3 nmol l -1 [2]. In contrast, the IC50 of sorafenib, sunitinib and pazopanib against VEGFR 1-3 was at least 10-fold greater, at 2-90 nmol l -1 [33]. The IC50 of axitinib for other non-VEGFR TKIs (e.g.…”

Section: Figurementioning

confidence: 99%

Incidence and risk of hypertension with a novel multi‐targeted kinase inhibitor axitinib in cancer patients: a systematic review and meta‐analysis

Shen

et al. 2013

Brit J Clinical Pharma

107

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AIMSTo investigate the overall incidence and risk of hypertension in cancer patients who receive axitinib and compare the differences in incidences between axitinib and the other four approved vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitors (TKIs). METHODSSeveral databases were searched, including Pubmed, Embase and Cochrane databases. Eligible studies were phase II and III prospective clinical trials of patients with cancer assigned axitinib at a starting dose of 5 mg orally twice daily with data on hypertension available. Overall incidence rates, relative risk (RR), and 95% confidence intervals (CI) were calculated employing fixed or random effects models depending on the heterogeneity of the included trials. RESULTSA total of 1908 patients from 10 clinical trials were included. The overall incidences of all grade and high grade hypertension in cancer patients were 40.1% (95% CI 30.9, 50.2%) and 13.1% (95% CI 6.7, 24%). The use of axitinib was associated with significantly increased risk of all grade (RR 3.00, 95% CI 1.29, 6.97, P = 0.011) and high grade hypertension (RR1.71, 95% CI 1.21, 2.43, P = 0.003). The risk of axitinib associated all grade and high grade hypertension in renal cell carcinoma (RCC) was significantly higher than that in non-RCC. Additionally, the risk of hypertension with axitinib was substantially higher than other approved VEGFR-TKIs, while the risk of all grade hypertension with axitinib was similar to pazopanib (RR 1.05; 95% CI 0.95-, 1.17, P = 0.34). CONCLUSIONSWhile sharing a similar spectrum of target receptors with other VEGFR-TKIs, axitinib is associated with an unexpectedly high risk of developing hypertension. Close monitoring and appropriate management for hypertension are recommended during the treatment. WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT• The use of vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitors (TKIs) is associated with an increased risk of developing hypertension. Axitinib is a novel, selective VEGFR-TKI, but its overall incidence and risk of developing hypertension is still unknown. WHAT THIS STUDY ADDS• The use of axitinib is associated with an unexpectedly high risk of developing hypertension when compared with the other four approved VEGFR-TKIs. Close monitoring and appropriate management for hypertension are recommended during treatment.

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“…2,3 Among these, the most recent addition to the mRCC treatment guidelines is axitinib, an oral, multitargeted TKI, which inhibits vascular endothelial growth factor (VEGF) receptors 1, 2, and 3 at subnanomolar concentrations in vitro. 4 Agents in development such as tivozanib, dovitinib, and lenvatinib will not be discussed in this paper.…”

mentioning

confidence: 98%

Axitinib for the Treatment of Metastatic Renal Cell Carcinoma

Larkin¹,

Fishman

Wood

et al. 2014

American Journal of Clinical Oncology

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Axitinib is a novel, oral, multitargeted tyrosine kinase inhibitor, which inhibits vascular endothelial growth factor receptors 1, 2, and 3 at subnanomolar concentrations in vitro. In the phase III clinical trial in patients with metastatic renal cell carcinoma, axitinib showed a high objective response rate, and significantly prolonged progression-free survival compared with sorafenib. Thus, it is the first drug that has proven the concept of sequencing tyrosine kinase inhibitors in second-line treatment in a phase III prospective randomized trial. Although generally well tolerated and associated with a low incidence of grade 3 or 4 toxicities, axitinib shows a distinct pattern of adverse events that require monitoring and management. The most common adverse events observed with axitinib include diarrhea, hypertension, fatigue, nausea, and vomiting. This article summarizes the most important adverse events observed and proposes recommendations for their monitoring, prevention, and treatment. The recommendations are based on the existing literature and discussion by an expert group of international physicians and nurses specialized in oncologic treatment of metastatic renal cell carcinoma, which gathered in July 2011 in London, UK. Proactive assessment and management of adverse events during axitinib therapy can minimize treatment interruptions and ensure optimal effect of treatment.

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Axitinib for the Management of Metastatic Renal Cell Carcinoma

Cited by 16 publications

References 53 publications

Chronic arterial hypertension impedes glioma growth: a multiparametric MRI study in the rat

Chronic arterial hypertension impedes glioma growth: a multiparametric MRI study in the rat

Incidence and risk of hypertension with a novel multi‐targeted kinase inhibitor axitinib in cancer patients: a systematic review and meta‐analysis

Axitinib for the Treatment of Metastatic Renal Cell Carcinoma

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