Hypertension Management in Patients with Renal Cell Cancer Treated with Anti-Angiogenic Agents

Larochelle, Pierre; Kollmannsberger, Christian; Feldman, Ross D.; Schiffrin, Ernesto L.; Poirier, Luc; Patenaude, François; Ruether, Dean; Myers, Martin G.; Bjarnason, Georg A.

doi:10.3747/co.19.972

Cited by 26 publications

(32 citation statements)

References 28 publications

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“…Hand-foot skin reaction (HFSR) is the most common [11][12][13][14]56,57] and dose-limiting toxicity of sorafenib [35,58]. HFSR is characterized by tender palmar-plantar lesions such as erythema, oedema and pain on the palms of the hands and/ or the soles of the feet.…”

Section: Hand-foot Skin Reaction (Hfsr)mentioning

confidence: 99%

“…Once treatment has begun, patients are advised to have their blood pressure measured on a weekly basis. Hypertension can be managed with standard antihypertensive agents, such as angiotensin-converting enzyme (ACE) inhibitors and b-blockers, without a dose reduction of sorafenib [34,35]. Temporary or permanent discontinuation of sorafenib therapy should be considered in patients who develop severe and persistent hypertension.…”

Section: Hypertensionmentioning

confidence: 99%

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The Adverse Effects of Sorafenib in Patients with Advanced Cancers

Gao

2015

Basic Clin Pharma Tox

134

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Sorafenib is the first multi-kinase inhibitor (TKI) approved for the treatment of advanced hepatocellular cancer (HCC) and metastatic renal cell cancer (RCC) and is increasingly being used to treat patients with well-differentiated radioiodine-resistant thyroid cancer (DTC). Sorafenib demonstrates targeted activity on several families of receptor and non-receptor tyrosine kinases that are involved in angiogenesis, tumour growth and metastatic progression of cancer. Sorafenib treatment results in longterm efficacy and low incidence of life-threatening toxicities. Although sorafenib has demonstrated many benefits in patients, the adverse effects cannot be ignored. The most common treatment-related toxicities include diarrhoea, fatigue, hand-foot skin reaction and hypertension. Most of these toxicities are considered mild to moderate and manageable to varying degrees; however, cardiovascular events might lead to death. In this MiniReview, we summarize the adverse effects of sorafenib that commonly occur in patients with advanced cancers.Over the past few years, targeted therapy utilizing multi-tyrosine kinase inhibitors (TKIs) has been widely used for treatment of cancers. TKIs are designed to block specific cancer cell processes and are usually better tolerated than most conventional chemotherapeutic drugs. Sorafenib is the first orally active TKI approved by the Food and Drug Administration (FDA). Sorafenib mainly targets vascular endothelial growth factor (VEGFR1-3) and Raf kinases. Other reported targets include K-Ras, BRAF, V599E mutant BRAF, platelet-derived growth factor receptor-b (PDGFR-b), FMS-like tyrosine kinase 3 (FLT3), c-Kit and RET, and several other receptor tyrosine kinases (RTKs) via various modes of action, such as inhibition of the Ras/Raf/MAPK and PI3K/AKT/mTOR signalling pathways [1][2][3]. The anticancer activity of sorafenib thus results from a dual inhibitory effect towards angiogenesis and tumour cell proliferation. Sorafenib also possesses the function of inducing apoptosis in cancer cells by inhibiting the phosphorylation of initiation factor eIF4E and loss of the antiapoptotic protein myeloid cell leukaemia-1(Mcl-1) [4].In 2007, sorafenib was approved by the FDA for the treatment of advanced hepatocellular cancer (HCC) [5,6] and metastatic renal cell cancer (RCC) [7,8]. Oral administration of sorafenib is associated with improved quality of life and prolonged overall survival of patients [9]. Recently, the most positive phase III results were observed in well-differentiated radioiodine-resistant thyroid cancer (DTC) [10], resulting in the increased use of sorafenib to treat patients with DTC.

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Section: Hand-foot Skin Reaction (Hfsr)mentioning

confidence: 99%

Section: Hypertensionmentioning

confidence: 99%

The Adverse Effects of Sorafenib in Patients with Advanced Cancers

Gao

2015

Basic Clin Pharma Tox

134

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“…Antiangiogenic agents are frequently used in treating cancer. One side effect of this therapy is hypertension (14). This effect may be similar to the effect shown in preeclampsia in which plasma levels of fms-like tyrosine kinase 1 (sFlt1), an antagonist of VEGF, are elevated (15).…”

Section: Introductionmentioning

confidence: 53%

Rapid Decreases in Blood Pressure from Antihypertensive Treatment were Associated with Increased Cancer Mortality in the Systolic Hypertension in the Elderly Program

Swerdel

Janević

Cabrera

et al. 2014

Cancer Epidemiology, Biomarkers &Amp; Prevention

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Background: Research on the association between antihypertensive drug treatment (HTDT) and cancer is equivocal. We tested the hypothesis that large, rapid decreases in blood pressure following HTDT are associated with higher cancer mortality.Methods: Data from the Systolic Hypertension in the Elderly Program (SHEP) with 15-year cause-specific follow-up for mortality were used. We used changes from baseline in seated and standing systolic blood pressure (SBP) measurements at 3, 6, 9, and 12 months after the initiation of HTDT. Hazard ratios adjusted for demographics, comorbidities, and competing risk of non-cancer-related deaths were estimated to determine the association between SBP change, as a continuous or time-dependent measure, and cancer-related death.Results: SHEP participants taking antihypertensive medication who exhibited a decrease in seated SBP of 29 mm Hg or more (50th percentile and above) at 3 months were at a 58% greater risk of cancer-related death during a 15-year follow-up compared with those with no decrease in SBP (P ¼ 0.007, 42% increased risk P ¼ 0.02 for standing SBP). Those participants whose maximal seated SBP change occurred in the first 3 months of treatment had 2.6-times greater risk of cancer mortality compared with those whose maximal seated SBP change occurred at 12 months (P ¼ 0.004).Conclusions: Large SBP decreases early in HTDT were associated with an increased risk of cancer-related death during a 15-year follow-up. Further studies are needed to confirm and explore the potential mechanisms for this association.Impact: Rapid decreases in blood pressure following HTDT may be a risk factor for cancer. Cancer Epidemiol Biomarkers Prev; 23(8); 1589-97. Ó2014 AACR.

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“…52,55 When using calcium channels blockers (CCBs), nondihydropyridine CCBs such as diltiazem or verapamil should be avoided, as they inhibit cytochrome P450 3A4, which metabolizes VEGF inhibitors, leading to high levels of plasma VEGF inhibitors. 52,56 Diarrhea is a common AE in TKI-treated patients. The incidence of any grade of diarrhea was 39% in the REFLECT trial.…”

Section: Management Of Aes During Treatment With Lenvatinibmentioning

confidence: 99%

“…Both ARB and ACEi are recommended in patients with proteinuria, which is another AE of lenvatinib, because of their renoprotective effects . When using calcium channels blockers (CCBs), non‐dihydropyridine CCBs such as diltiazem or verapamil should be avoided, as they inhibit cytochrome P450 3A4, which metabolizes VEGF inhibitors, leading to high levels of plasma VEGF inhibitors …”

Section: Introductionmentioning

confidence: 99%

Novel approaches for molecular targeted therapy against hepatocellular carcinoma

Eso

Marusawa

2018

Hepatology Research

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Systemic chemotherapy using a multitargeted tyrosine kinase inhibitor is an established treatment for advanced-stage tumors in various organs. Comprehensive genomic analyses using next-generation sequencing technology revealed the intra- and intertumor heterogeneity of human hepatocellular carcinomas (HCCs), and provided evidence for the use of therapeutic agents effective against multiple targets in tumor cells. Recently, the efficacy and safety of a multitargeted tyrosine kinase inhibitor, lenvatinib, was confirmed by a randomized global phase III trial; thus, lenvatinib was approved as first-line therapy for HCC, providing a new therapeutic option for patients at an advanced stage. In this article, we introduce the application of molecular targeted therapy using lenvatinib and discuss future aspects of therapeutic options for advanced HCC.

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Hypertension Management in Patients with Renal Cell Cancer Treated with Anti-Angiogenic Agents

Cited by 26 publications

References 28 publications

The Adverse Effects of Sorafenib in Patients with Advanced Cancers

The Adverse Effects of Sorafenib in Patients with Advanced Cancers

Rapid Decreases in Blood Pressure from Antihypertensive Treatment were Associated with Increased Cancer Mortality in the Systolic Hypertension in the Elderly Program

Novel approaches for molecular targeted therapy against hepatocellular carcinoma

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