Could thyroid dysfunction influence outcome in sunitinib-treated metastatic renal cell carcinoma?

Sabatier, Renaud; Eymard, J-C.; Walz, Jochen; Deville, Jean‐Laurent; Narbonne, H.; Boher, Jean-Marie; Salem, Naji; Marcy, M.; Brunelle, Serge; Viens, Patrice; Bladou, Franck; Gravis, Gwénaëlle

doi:10.1093/annonc/mdr275

Cited by 61 publications

(61 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…So this study demonstrated the importance of achieving and maintaining optimal exposure to sunitinib. Despite these described evidences, Sabatier et al (2012) in a prospective observational multicenter study have shown that abnormal thyroid function did not increase survival among patients with mRCC treated with sunitinib. In fact, among 102 patients with normal baseline thyroid function, 53% developed thyroid dysfunction and median PFS was not different between the groups with abnormal or normal thyroid function after 6 months of treatment (18.9 and 15.9 months respectively).…”

Section: Hypothyroidism and Tumor's Outcomementioning

confidence: 86%

“…In prospective and observational studies, this complication has been reported in 53-85% of patients (Table 3; Desai et al 2006, Mannavola et al 2007, Wolter et al 2008, Riesenbeck et al 2011, Schmidinger et al 2011, Baldazzi et al 2012, Sabatier et al 2012.…”

Section: Sunitinibmentioning

confidence: 96%

“…Schmidinger et al (2011) showed a statistically significant improvement of OS but not of PFS in hypothyroid patients. It was not specified what therapies were carried out after progression with sunitinib or sorafenib in hypothyroid and euthyroid patients, and how these treatments could have modified OS (Sabatier et al 2012). Instead, Sabatier et al (2012) tried to cancel all these bias.…”

Section: Hypothyroidism and Tumor's Outcomementioning

confidence: 99%

“…Moreover, fatigue may also be a direct hypothyroidism consequence. However, it is important to identify the etiology of TKIassociated asthenia, in particular, if it is related to a curable cause (Sabatier et al 2012).…”

Section: Tki's Hypothyroidism and Its Managementmentioning

confidence: 99%

See 3 more Smart Citations

Thyroid dysfunction and tyrosine kinase inhibitors in renal cell carcinoma

Bianchi¹,

Rossi²,

Tomao³

et al. 2013

Endocrine-Related Cancer

View full text Add to dashboard Cite

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.

show abstract

Section: Hypothyroidism and Tumor's Outcomementioning

confidence: 86%

Section: Sunitinibmentioning

confidence: 96%

Section: Hypothyroidism and Tumor's Outcomementioning

confidence: 99%

Section: Tki's Hypothyroidism and Its Managementmentioning

confidence: 99%

See 2 more Smart Citations

Thyroid dysfunction and tyrosine kinase inhibitors in renal cell carcinoma

Bianchi¹,

Rossi²,

Tomao³

et al. 2013

Endocrine-Related Cancer

View full text Add to dashboard Cite

show abstract

“…Whether prolonged treatment with a TKI, or previous treatments with cytokines (i.e., IFN/IL-2) or another TKI might influence the incidence or the course of thyroid dysfunction remains to be clarified. Among TKI approved for clinical use, sunitinib, a TKI mainly targeting angiogenic kinase-receptors, exposes patients to a higher risk of developing TKI hypothyroidism (14-71% of patients in prospective studies) (146)(147)(148)(149)(150)(151)(152)(153). Thyroid dysfunction has also been described with other antiangiogenic TKI, such as sorafenib, motesanib, pazopanib, cediranib, and linifarib, but at lower rates (Table 2).…”

Section: Tyrosine Kinase Inhibitorsmentioning

confidence: 99%

Thyroid Dysfunction as an Unintended Side Effect of Anticancer Drugs

Torino

Barnabei²,

Paragliola

et al. 2013

Thyroid

101

View full text Add to dashboard Cite

CRISPR‐mediated knockout of VEGFR2/KDR inhibits cell growth in a squamous thyroid cancer cell line

et al. 2022

View full text Add to dashboard Cite

Squamous and anaplastic thyroid cancers are the most aggressive and life‐threatening cancer types in humans, with the involvement of lymph nodes in 59% of cases and distant metastases in 26% of cases of all thyroid cancers. The median survival of squamous thyroid cancer patients is < 8 months and therefore is of high clinical concern. Here, we show that both VEGFC and VEGFR2/KDR are overexpressed in thyroid cancers, indicating that VEGF/VEGFR signaling plays a carcinogenic role in thyroid cancer development. Using CRISPR/Cas9, we established a KDR knockout (KO) SW579 squamous thyroid cancer cell line that exhibited dramatically decreased colony formation and invasion abilities (30% and 60% reduction, respectively) when compared to scrambled control cells. To validate the potential of KDR as a therapeutic target for thyroid cancers, we used the KDR RTK inhibitor sunitinib. Protein analysis and live/dead assay were performed to demonstrate that sunitinib significantly inhibited cell growth signal transduction and induced cell apoptosis of SW579 cells. These results suggest that selective targeting of KDR may have potential for development into novel anti‐cancer therapies to suppress VEGF/VEGFR‐mediated cancer development in patients with clinical advanced thyroid cancer.

show abstract

Could thyroid dysfunction influence outcome in sunitinib-treated metastatic renal cell carcinoma?

Cited by 61 publications

References 29 publications

Thyroid dysfunction and tyrosine kinase inhibitors in renal cell carcinoma

Thyroid dysfunction and tyrosine kinase inhibitors in renal cell carcinoma

Thyroid Dysfunction as an Unintended Side Effect of Anticancer Drugs

CRISPR‐mediated knockout of VEGFR2/KDR inhibits cell growth in a squamous thyroid cancer cell line

Contact Info

Product

Resources

About