The safety of vandetanib for the treatment of thyroid cancer

Tsang, Venessa; Robinson, Bruce G.; Learoyd, Diana

doi:10.1080/14740338.2016.1201060

Cited by 27 publications

(17 citation statements)

References 27 publications

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“…As some TKIs can induce hepatic and renal toxicities, it is important to monitor hepatic and renal function in patients receiving potentially hepatotoxic or nephrotoxic drugs (98)(99)(100)(101)(102)(103)(104)(105)(106)(107)(108)(109)(110)(111)(112)(113)(114)(115). If prescription of a hepatotoxic or nephrotoxic drug is necessary for patients with HI or RI, and there are no better tolerated alternatives, preventive methods, including hepatic and renal function monitoring, adverse reactions monitoring and appropriate dosage adjustment, should be considered.…”

Section: Discussionmentioning

confidence: 99%

Dose adjustment for tyrosine kinase inhibitors in non‑small cell lung cancer patients with hepatic or renal function impairment (Review)

Zhao¹,

Chen²,

Long³

et al. 2020

Oncol Rep

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In recent years, a number of tyrosine kinase inhibitors (TKIs) have been approved for the treatment of non-small cell lung cancer. These novel treatments exhibit improved efficacy and toxicity when compared to conventional chemotherapy agents. TKIs are administered orally, which has the advantages of improved flexibility and convenience for the patients. However, challenges have arisen in the use of these novel agents. Prescribing drugs for patients with hepatic or renal function impairment poses a challenge for clinicians due to the large pharmacokinetic variability in each individual patient. Moreover, several TKIs have been shown to cause laboratory test abnormalities normally associated with hepatic or renal injury. The aim of the present review was to discuss the effects of hepatic and renal function impairment on the pharmacokinetic variability of 17 TKIs and their potential hepatotoxicity and nephrotoxicity, and to recommend dose adjustment for patients with hepatic or renal impairment.

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Section: Discussionmentioning

confidence: 99%

Dose adjustment for tyrosine kinase inhibitors in non‑small cell lung cancer patients with hepatic or renal function impairment (Review)

Zhao¹,

Chen²,

Long³

et al. 2020

Oncol Rep

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“…Notably, vandetanib caused a remarkable inhibition of SARS-CoV-2 propagation in our study against all clades of SARS-CoV-2. Vandetanib, an FDA-approved EGFR inhibitor, is an inexpensive drug with low toxicity that has been used for the treatment of certain tumours of the thyroid gland 52,53 .…”

Section: Discussion 251mentioning

confidence: 99%

SARS-CoV-2 aberrantly elevates mitochondrial bioenergetics to induce robust virus propagation

Shin

Yoon

et al. 2021

Preprint

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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a respiratory pathogen leading to serious multi-organ damage. However, little is known about SARS-CoV-2-induced cellular alterations for understanding robust virus propagation yet. Here we report that SARS-CoV-2 aberrantly elevates mitochondrial bioenergetics and activates epidermal growth factor receptor (EGFR)-mediated cell survival signal cascade for sustaining persistence of SARS-CoV-2. We found that SARS-CoV-2 causes increase in mitochondrial transmembrane potential by SARS-CoV-2 RNA-nucleocapsid cluster, thereby abnormally promoting mitochondrial biogenesis and oxidative phosphorylation (OXPHOS) process followed by abundant ATP production. SARS-CoV-2 also activated EGFR signal cascade and subsequent mitochondrial EGFR accumulation which contributes to the maintenance of abnormal OXPHOS and viral propagation. Therapeutic options for the treatment of COVID-19 are still inadequate. The FDA-approved EGFR inhibitors caused a remarkable reduction in SARS-CoV-2 propagation. Among EGFR inhibitors, vandetanib showing the highest anti-SARS-CoV-2 efficacy exhibited the potent antiviral activity against various SARS-CoV-2 variants including B.1.1.7 (UK variant) and B.1.351 (SA variant) lineages in both in vitro cell culture and in vivo animal experiments using wild-type aged mouse susceptible to SARS-CoV-2 infection, suggesting that EGFR is an attractive host target for combatting COVID-19. Overall, our results suggest that SARS-CoV-2 induces aberrant mitochondrial dynamics and bioenergetics, which significantly contributes to robust SARS-CoV-2 propagation.

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“…Administration of vandetanib may prolong the QT interval and lead to cases of torsades de pointes and sudden deaths . Because of these risks, the compound can be prescribed by practitioners only after completion of the so‐called Risk Evaluation and Mitigation Strategy (REMS) Program, aiming at ensuring that benefits resulting from vandetanib prescription outweigh the known severe toxicities.…”

Section: Current Therapies In Thyroid Carcinomasmentioning

confidence: 99%

“…[73][74][75][76] Administration of vandetanib may prolong the QT interval and lead to cases of torsades de pointes and sudden deaths. 77 Because of these risks, the compound can be prescribed by practitioners only after completion of the socalled Risk Evaluation and Mitigation Strategy (REMS) Program, aiming at ensuring that benefits resulting from vandetanib prescription outweigh the known severe toxicities. Notwithstanding that, dose reduction is often required, as well as treatment discontinuation, due to life-threatening risks: 2% of patients treated to date with vandetanib experienced lethal toxicity.…”

Section: F I G U R E 5 Tyrosine Kinase Inhibitors Under Clinical Invementioning

confidence: 99%

Novel therapeutic clues in thyroid carcinomas: The role of targeting cancer stem cells

Antonelli

Motta

2017

Medicinal Research Reviews

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Thyroid carcinomas (TCs), the most common endocrine tumors, represent the eighth most common cancer diagnosed worldwide in both women and men. To treat these malignancies, several drugs are now available and a number of novel ones have been enrolling in clinical trials, addressing both oncogenic pathways in cancer cells and angiogenic pathways in tumor endothelial cells. However, their use is not devoid of serious toxicities and their efficacy is limited, being dependent on carcinoma typology and the occurrence of acquired resistance. Accordingly, it is time to recast therapeutic strategies against these types of tumors to get to newer and fully effective drugs. In this perspective, latest findings demonstrate that cancer stem cells (CSCs) represent a challenging target to strike. They possess core traits of self-renewal and differentiation, being resistant to the effects of chemotherapy and radiation and playing a key role in mediating metastasis. Therefore, basic molecular elements sustaining both development of thyroid cancer stem cells and their residence in the stemness condition represent a set of innovative and still unexplored targets to address. In this review, a thorough literature survey has been accomplished, to take stock of mechanisms governing thyroid carcinomas and to point out both their currently available treatments and the novel forthcoming ones. Pubmed, Scifinder and ClinicalTrials.gov were exploited as research applications and registry database, respectively. Original articles, reviews, and editorials published within the last ten years, as well as open clinical investigations in the field, were analyzed to suggest new exciting therapeutic opportunities for people affected by TCs.

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The safety of vandetanib for the treatment of thyroid cancer

Abstract: Vandetanib has an important role in the management of patients with progressive metastatic MTC. The use in patients with stable or asymptomatic disease has no proven benefit. The side effects can usually be managed with dose reduction, interruption, and/or specific symptomatic therapy.

Cited by 27 publications

References 27 publications

Dose adjustment for tyrosine kinase inhibitors in non‑small cell lung cancer patients with hepatic or renal function impairment (Review)

Dose adjustment for tyrosine kinase inhibitors in non‑small cell lung cancer patients with hepatic or renal function impairment (Review)

SARS-CoV-2 aberrantly elevates mitochondrial bioenergetics to induce robust virus propagation

Novel therapeutic clues in thyroid carcinomas: The role of targeting cancer stem cells

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