Thyroid Dysfunction in Patients Treated with Tyrosine Kinase Inhibitors, Sunitinib, Sorafenib and Axitinib, for Metastatic Renal Cell Carcinoma

Daimon, Makoto; Kato, Tomoyuki; Kaino, Wataru; Takase, Kaoru; Karasawa, Shigeru; Wada, Kiriko; Kameda, Wataru; Susa, Shinji; Oizumi, Toshihide; Tomita, Yoshihiko; Kato, Takeshi

doi:10.1093/jjco/hys076

Cited by 42 publications

(22 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…A transient decrease in TSH, suggesting a thyroiditis-induced thyrotoxic phase, was also identified in some of their patients. Several subsequent studies have confirmed a high frequency of axitinib-related thyroid dysfunction, ranging from 88% to 100% (2,7,8). Consistent with earlier reports, the six patients reported here developed thyroid dysfunction.…”

Section: Discussionsupporting

confidence: 91%

“…Thyroid dysfunction has also been described with other antiangiogenic agents, such as sorafenib and sunitinib, although at lower rates (1,3,8). In this study, the relationship between TSH and thyroid hormone levels was also evaluated in patients treated with sunitinib and sorafenib; the results showed a weaker tendency compared to the axitinib-treated patients.…”

mentioning

confidence: 86%

“…Axitinib is a potent and selective second-generation TKI that effectively blocks vascular endothelial growth factor (VEGF) receptors at subnanomolar concentrations (5). Although several studies have reported a high frequency of thyroid dysfunction in patients taking axitinib (2,(6)(7)(8), the associated mechanism and clinical features have not been determined. Here, we report six consecutive patients with metastatic renal cell carcinoma (RCC) that developed thyroid dysfunction during axitinib treatment.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Inappropriate Elevation of Serum Thyrotropin Levels in Patients Treated with Axitinib

Ohba

Takayama

Matsunaga

et al. 2013

Thyroid

View full text Add to dashboard Cite

show abstract

Section: Discussionsupporting

confidence: 91%

mentioning

confidence: 86%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Inappropriate Elevation of Serum Thyrotropin Levels in Patients Treated with Axitinib

Ohba

Takayama

Matsunaga

et al. 2013

Thyroid

View full text Add to dashboard Cite

show abstract

“…In a phase I/II trial, up to 89% patients showed increased TSH level [15]. Another study reported that the risk of hypothyroidism was higher for axitinib than for sorafenib and sunitinib (HR 4.53, p = 0.01) [16]. As the frequency and timing of hypothyroidism may differ for each TKI, TKIs should be considered individually.…”

Section: Discussionmentioning

confidence: 99%

Axitinib-Induced Hypothyroidism as a Predictor of Long-Term Survival in Patients with Metastatic Renal Cell Carcinoma

Takada¹,

Hashishita²,

Nagamori³

2019

Urol Int

View full text Add to dashboard Cite

Background: The side effects of sunitinib, namely onset of hypertension and hypothyroidism, have been reported to be predictive biomarkers of treatment efficacy. However, the relationship between hypothyroidism and prolongation of survival in treatment with axitinib, a drug similar to sunitinib, has not yet been reported. Objective: In this study, we examined the relationship between the onset of hypothyroidism caused by axitinib and overall survival (OS) and progression-free survival (PFS). Methods: In this retrospective study, 44 Japanese patients, including 30 men and 14 women, were enrolled. The average age of subjects in this study was 67 years. Results: During treatment, 68% of patients developed hypothyroidism, with an average peak thyroid-stimulating hormone (TSH) value of 15.7 mIU/L. Patients with TSH > 4 mIU/L and required thyroid hormone regulation with levothyroxine had prolonged PFS (11.1 vs. 3.5 months; p = 0.002) and OS (26.4 vs. 15.6 months; p = 0.02). Hypothyroidism was found to be a significant side effect of axitinib in patients with metastatic renal cell carcinoma (mRCC). Patients with hypothyroidism had significantly longer PFS and OS. Conclusion: Our findings indicate that hypothyroidism may be a predictive marker of therapeutic effect of axitinib against mRCC.

show abstract

“…45 In terms of thyroid dysfunction, a Japanese study observed that mRCC patients treated with axitinib developed incident thyroid dysfunction more commonly and within a shorter time frame when compared to those treated with sorafenib or sunitinib. 46 However, these findings were limited by the small retrospective nature of the study. Nevertheless, these findings together highlight the important toxicity considerations and clinical monitoring necessary while using axitinib.…”

mentioning

confidence: 93%

Axitinib in the treatment of renal cell carcinoma: patient selection and perspectives

Narayan

Haas

2016

IJNRD

View full text Add to dashboard Cite

Background: Axitinib is a next-generation, selective tyrosine kinase inhibitor targeting the vascular endothelial growth factor receptors. It is approved for the treatment of metastatic renal cell carcinoma (mRCC) based on a demonstrated progression-free survival advantage over sorafenib in the second-line treatment setting. However, given the variety of available targeted therapies for mRCC, appropriate patient selection for the available therapies remains a significant clinical challenge. Purpose: This review summarizes the available evidence on the clinical, toxicity, and pharmacologic considerations for determining appropriate patient selection for axitinib therapy. In addition, it describes recent data on the use of predictive biomarkers to guide clinical management. This paper consists of material obtained via PubMed and Medline literature searches through October 2015. Conclusion: Axitinib has a well-established role in the management of mRCC. Consistent clinical efficacy has been demonstrated across prognostic risk groups and prior therapeutic exposures. Although axitinib is generally well tolerated, appropriate toxicity management is critical to maximizing drug delivery and optimizing treatment outcomes. Although incident hypertension has been associated with improved clinical outcomes on axitinib, there are currently no validated clinical or genetic predictive biomarkers to guide patient selection.

show abstract

Thyroid Dysfunction in Patients Treated with Tyrosine Kinase Inhibitors, Sunitinib, Sorafenib and Axitinib, for Metastatic Renal Cell Carcinoma

Cited by 42 publications

References 18 publications

Inappropriate Elevation of Serum Thyrotropin Levels in Patients Treated with Axitinib

Inappropriate Elevation of Serum Thyrotropin Levels in Patients Treated with Axitinib

Axitinib-Induced Hypothyroidism as a Predictor of Long-Term Survival in Patients with Metastatic Renal Cell Carcinoma

Axitinib in the treatment of renal cell carcinoma: patient selection and perspectives

Contact Info

Product

Resources

About