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

BackgroundSunitinib 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.MethodsWe have evaluated 70 patients with mRCC that received sunitinib as a first line treatment. Thyroid-stimulating hormone (TSH) was measured at baseline, after 15days 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.ResultsRegarding the response to treatment, a progression-free survival (PFS) of 9.47months and an overall survival (OS) of 22.03months 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 (x3.33 times the baseline values on day-15) than patients that exhibited disease stabilisation (x2.18) or disease progression (x1.59). Early increases in TSH were associated with a longer PFS (11.92 vs. 8.82months, p=0.0476) and a longer OS (3.10 vs. 1.08years, p=0.0011).ConclusionsEarly 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.