Hypothyroidism as a predictive clinical marker of better treatment response to sunitinib therapy

Anticancer Res. 2014 Jun;34(6):3177-84.

Abstract

Background: Tyrosine kinase inhibitors are standard treatment in patients with metastatic renal cell carcinoma (mRCC). Several studies have indicated that side-effects including hypothyroidism may serve as potential predictive biomarkers of treatment efficacy.

Patients and methods: All patients with clear cell mRCC treated with sunitinib in the first-line setting in our Center between November 2008 and October 2013 were included. Thyroid function was assessed after every 2 cycles. Prognostic factors were tested using Cox proportional hazards model for univariate analysis.

Results: During treatment, 29.3% developed hypothyroidism, with a median of peak TSH values of 34.4 mIU/L. Patients who had both TSH >4 mIU/L and were receiving substitution therapy with levothyroxine had prolonged PFS compared to all other patients (25.3 months vs. 9.0 months; p=0.042).

Conclusion: The rate of hypothyroidism as a side-effect of sunitinib in patients with mRCC is significant. Patients with symptomatic hypothyroidism experienced significantly longer PFS, but without difference in OS.

Keywords: Clinical markers; hypothyroidism; levothyroxine substitution therapy; predictive factor; renal cell carcinoma; sunitinib.

MeSH terms

  • Aged
  • Antineoplastic Agents / therapeutic use*
  • Biomarkers, Tumor / analysis*
  • Carcinoma, Renal Cell / drug therapy*
  • Carcinoma, Renal Cell / secondary
  • Cohort Studies
  • Female
  • Follow-Up Studies
  • Humans
  • Hypothyroidism / chemically induced
  • Hypothyroidism / diagnosis*
  • Indoles / therapeutic use*
  • Kidney Neoplasms / drug therapy*
  • Kidney Neoplasms / pathology
  • Male
  • Neoplasm Metastasis
  • Neoplasm Staging
  • Pyrroles / therapeutic use*
  • Sunitinib
  • Survival Rate
  • Treatment Outcome

Substances

  • Antineoplastic Agents
  • Biomarkers, Tumor
  • Indoles
  • Pyrroles
  • Sunitinib

Supplementary concepts

  • Clear-cell metastatic renal cell carcinoma