Chronic tyrosine kinase inhibitor (TKI) use in metastatic renal cell carcinoma (mRCC): can this lead to the adverse effect of hypogonadism?

ABSTRACT

Background: Patients with metastatic renal cell carcinoma (mRCC) are commonly treated with tyrosine kinase inhibitors (TKIs). An adverse effect frequently suffered by patients is lethargy, which often leads to dose reduction or drug cessation. We aimed to assess whether hypogonadism is related to treatment with TKIs.

Methods: We prospectively assessed gonadal function in 41 consecutive males with mRCC treated with TKIs. Demographic, clinical, and biochemical variables were collected, and statistical analyses performed to assess correlation and survival. Data Capture for each patient was perfomred at the time of entry in the study.

Results: There was a 77% incidence of hypogonadism in this cohort. Assessment of testosterone level and time on TKI treatment revealed a correlation with linear regression R² of 0.24 and regression coefficient of −0.003 (p = 0.019). Odds ratio for hypogonadism at >30 months on TKIs was 12.1 (p = 0.011). Odds ratios above and below this value showed a confirmatory trend, suggesting that this may be a chronic adverse effect.

Conclusions: Our findings provide an important and robust hypothesis for a prospective clinical trial to be performed.

Expert Opinion: Given the present data, patients who have symptoms suggestive of hypogonadism must have an assessment of gonadal function and be treated.

KEYWORDS:

• Tyrosine kinase inhibitors
• hypogonadism
• renal cell carcinoma
• testosterone
• lethargy

Article highlights

• Question: Do TKIs cause hypogonadism?

• Finding: Certain TKIs used chronically are likely to cause hypogonadism

• Meaning: Any health-care professional involved in the care pathway of mRCC patients on TKI therapy must be aware of the risk of hypogonadism in these patients.

Declaration of interest

The authors declare consultancy fees and honoraria from Pfizer, Novartis and Bayer plc.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Author contributions

M Afshar: Study design, patient enrolment, data collection, data analysis, document writing

HRH Patel: Document writing and review

A Jain: Data collection, Patient enrolment, document writing

A Kumar: Statistical analysis

P Patel: Document writing and review

ND James: Document writing and review

E Porfiri: Study concept, design, patient enrolment, document writing

Additional information

Funding

This paper was not funded.