Pazopanib: An Oral Multitargeted Tyrosine Kinase Inhibitor for Use in Renal Cell Carcinoma

LaPlant, Kourtney; Louzon, Paige D

doi:10.1345/aph.1m251

Cited by 13 publications

(5 citation statements)

References 21 publications

(5 reference statements)

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“…A review of the literature [46] identified thyroid dysfunction attributable to pazopanib with an incidence of 7% in patients treated for mRCC. The incidence and severity of thyroid dysfunction were explored in 578 pazopanib-treated patients participating in 3 trials, and it was found that 37 patients (6%) had elevated TSH at baseline (>5 mU/L), 167 (29%) had a TSH value of >5 mU/L during treatment.…”

Section: Pazopanibmentioning

confidence: 99%

Thyroid dysfunctions induced by tyrosine kinase inhibitors

Fallahi

Ferrari

Vita

et al. 2014

Expert Opin. Drug Saf.

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Section: Pazopanibmentioning

confidence: 99%

Thyroid dysfunctions induced by tyrosine kinase inhibitors

Fallahi

Ferrari

Vita

et al. 2014

Expert Opin. Drug Saf.

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“…Patients treated with sunitinib have a twofold increased risk of requiring thyroid hormone replacement therapy compared with sorafenib. Hypothyroidism was not listed as a common AE in phase III studies of sorafenib or pazopanib (Escudier et al 2007a, 2009, Sternberg et al 2010; however, a randomized, double-blinded, placebocontrolled phase III study (La Plant & Louzon 2010) identified thyroid dysfunction attributable to pazopanib with an incidence of fewer than 10% (%7%) in patients treated for mRCC, with grade 3/4 events reported in !1% of patients (Sternberg et al 2010). These results have been confirmed by another randomized, open-label, phase III trial of pazopanib vs sunitinib (Motzer et al 2012) where hypothyroidism occurred among 12% of patients treated with pazopanib (Table 3; Motzer et al 2012).…”

Section: Sorafenib and Pazopanibmentioning

confidence: 99%

“…The newer agent, axitinib, is a potent, selective, second-generation inhibitor of VEGFR-1, 2, and 3 , Cohen et al 2008, Schiller et al 2009, Torino et al 2009, La Plant & Louzon 2010, Rugo et al 2011. A recent pivotal phase III trial randomized a total of 723 patients with advanced RCC in order to compare axitinib and sorafenib as second-line therapy (Table 1; Rini et al 2011).…”

Section: Introductionmentioning

confidence: 99%

Thyroid dysfunction and tyrosine kinase inhibitors in renal cell carcinoma

Bianchi¹,

Rossi²,

Tomao³

et al. 2013

Endocrine-Related Cancer

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The most recent World Health Organization classification of renal neoplasms encompassed nearly 50 distinctive renal neoplasms. Different histological subtypes have different clinical outcomes and show different responses to therapy. Overall, the incidence of kidney cancer has increased worldwide in the last years. Although the most common type of kidney cancer is localized renal cell carcinoma (RCC), with a 5-year survival rate of 85%, about one third of patients present advanced or metastatic disease at diagnosis, with a 5-year survival rate of only 10%. Multi-targeted receptor tyrosine kinase inhibitors (TKIs, sunitinib and sorafenib), the anti-VEGF MAB bevacizumab in association with interferon-a, and the mTOR inhibitors are now approved for the treatment of mRCC. Recently, the novel agents pazopanib and axitinib have also demonstrated efficacy in mRCC patients. Several recent retrospective and prospective trials have suggested that some of their adverse events, such as hypertension, hypothyroidism, and hand foot syndrome (HFS) may act as potential biomarkers of response and efficacy of treatment. In this review, we analyzed the studies that have suggested a relationship between hypothyroidism onset and a better outcome of mRCC patients treated with TKIs. The biological mechanisms suggesting and explaining this correlation are not well known and different speculative theories have been considered in order to investigate the clinical link between hypothyroidism occurrence and the prolonged therapy with TKIs in solid tumors. Furthermore, the management of this unexplained side effect is very important to maximize the efficacy of therapy in mRCC patients because there is a clear and consistent relationship between drug dose and efficacy of treatment. Certainly, other studies are needed to clarify whether a better outcome is associated with hypothyroidism induced to TKIs in patients with mRCC.

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“…Studies indicated that tyrosine kinase inhibitors lead to thyroid dysfunction in various extent 20,21 , however its mechanism is still not clearly understood. 22 In this study, 8 out of 55 patients (14.5%) were diagnosed with thyroid dysfunction related to TKIs and TSH levels were at normal range after an initiation of levothyroxine treatment.…”

Section: Discussionmentioning

confidence: 99%

Clinical Pharmacy Practices in Oncology Patients Treated with Tyrosine Kinase Inhibitors

Bayraktar-Ekincioglu¹

2018

UHOD

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Tyrosine kinase inhibitors (TKIs) have a good efficacy profile in treatment of cancers but also have a potential risk for drug interactions and adverse effects. The aim of this study was to identify and evaluate drug-drug interactions and adverse effects related to TKIs in patients by the involvement of a clinical pharmacist within an outpatient setting. This study was conducted at an outpatient clinic of the University Oncology Hospital between October 2015 and April 2016. The patients on TKIs treatment were included and monitored during 3 months by a clinical pharmacist. The severity and a clinical significance of drug interactions were assessed by using different information resources. An occurrence of adverse effects in patients was evaluated in the first and the second visits. Fifty-five patients were included in the study. A total of 92 drug interactions were identified, of those 54 (58.69%) were assessed as a clinically significant. Among clinically significant drug interactions, a pharmacist recommended treatment modifications for 18 drug interactions, all were accepted by doctors and necessary modifications were implemented. Adverse effects (n= 32) were identified in 55 patients during the 3 months where a pharmacist made 32 recommendations, of which 29 (91%) were accepted by doctors. Statistically significant decrease was found in the number of occurred gastrointestinal disorders (p= 0.001) and fatigue (p= 0.021) between the first and the second visits. Close monitoring of patients by clinical pharmacists whom are integrated into the outpatient settings may further contribute to the health outcomes in collaboration with a multidisciplinary team in oncology.

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Pazopanib: An Oral Multitargeted Tyrosine Kinase Inhibitor for Use in Renal Cell Carcinoma

Cited by 13 publications

References 21 publications

Thyroid dysfunctions induced by tyrosine kinase inhibitors

Thyroid dysfunctions induced by tyrosine kinase inhibitors

Thyroid dysfunction and tyrosine kinase inhibitors in renal cell carcinoma

Clinical Pharmacy Practices in Oncology Patients Treated with Tyrosine Kinase Inhibitors

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