Ιmpact of sunitinib-induced hypothyroidism on survival of patients with metastatic renal cancer

Theofanis VasileiadisEmail author,
Michail Chrisofos,
Michail Safioleas,
Konstantinos Kontzoglou,
Konstantinos Papazisis and
Athina Sdrolia

BMC Cancer201919:407

https://doi.org/10.1186/s12885-019-5610-8

Received: 10 July 2017
Accepted: 12 April 2019
Published: 30 April 2019

Open Peer Review reports

Abstract

Background

Sunitinib plays an important role in managing the metastatic renal cell cancer (mRCC). Sunitinib-induced hypothyroidism is a common side-effect of the drug. There have been attempts to link hypothyroidism with a better clinical outcome in sunitinib-treated (mRCC) patients. Our aim was to relate the impact of hypothyroidism to the survival of these patients.

Methods

We have evaluated 70 patients with mRCC that received sunitinib as a first line treatment. Thyroid-stimulating hormone (TSH) was measured at baseline, after 15 days of treatment (day-15) and at the end of the second cycle (day-75).

Biomarker data and correlations with response were analysed with Microsoft Excel. Comparison results from Student’s t-test with a p less than 0.05 were considered statistically significant. Kaplan-Meyer and log-rank tests were performed using GraphPad Prism 5 for Windows.

Results

Regarding the response to treatment, a progression-free survival (PFS) of 9.47 months and an overall survival (OS) of 22.03 months were demonstrated. Our data are consistent with published data by other authors.

On day-15 from the beginning of the treatment an important number of patients exhibited a TSH elevation. On day-15 42.86% had a TSH over the upper normal limit and 50.0% at the end of the second cycle (day-75).

TSH increased earlier in patients that exhibited an objective response (× 3.33 times the baseline values on day-15) than patients that exhibited disease stabilisation (× 2.18) or disease progression (× 1.59). Early increases in TSH were associated with a longer PFS (11.92 vs. 8.82 months, p = 0.0476) and a longer OS (3.10 vs. 1.08 years, p = 0.0011).

Conclusions

Early TSH-increase is associated with a clinical benefit. The patients that showed at least a twofold increase of their baseline TSH, responded to therapy by stabilisation or by regression of disease.

This is the only study to our knowledge which shows that early increases - 2 weeks from starting the treatment - in TSH levels have a prognostic value. Both PFS and OS of the patients who demonstrated a higher than a twofold rise were significantly longer than the PFS and the OS of the patients that presented a lower or no TSH-increase.