title: Hypothyroidism correlates with a better prognosis in metastatic renal cancer patients treated with sorafenib or sunitinib.
abstract: OBJECTIVE
  To investigate prognostic markers in patients with metastatic renal cell carcinoma (mRCC) undergoing treatment with the tyrosine kinase inhibitors (TKIs) sorafenib (So) or sunitinib (Su).
  
  
  METHODS
  Eighty-three patients with mRCC, who were treated at our institution between 2006 and 2009, were evaluated prospectively. Clinical and laboratory parameters were investigated, as well as, treatment-related adverse events. Subclinical hypothyroidism was characterized by serum TSH above the upper limit of normal and both total triiodothyronine (T3) and thyroxine (T4) within normal limits. Clinical hypothyroidism was defined as low serum T3 and T4 together with elevated TSH.
  
  
  RESULTS
  Thirty-one (37.3%) patients received So, and 52 (62.7%) were treated with Su. In univariate analysis, the ECOG status (P < 0.0001) as well as MSKCC criteria (P = 0.003) and response to therapy (P < 0.0001) were associated with progression-free survival (PFS). Twenty-one of 66 (31.8%) evaluable patients developed hypothyroidism during treatment. Of those patients, 8/21 (38.1%) were treated with So and 13/21 (61.9%) with Su. Response rate in this subgroup was 49.2%. Hypothyroidism was associated with a longer PFS (16.0 ± 0.8 months vs. 6.0 ± 0.8 months, P = 0.032). Most patients [16/21 (76.2%)] developed abnormal TSH values during the first 4 weeks of treatment. Hormone replacement with l-thyroxine did not have an influence on survival. In multivariate analyses, only the ECOG status (ECOG 0/1 vs. ECOG 2, P = 0.018) and hypothyroidism (P = 0.01) were independent prognostic parameters.
  
  
  CONCLUSIONS
  The development of hypothyroidism during treatment might be useful as a predictor of PFS for mRCC patients undergoing treatment with targeted agents.
authors.affiliation: Department of Urology, University of Münster, Albert-Schweitzer Strasse 33, 48149, Münster, Germany.
authors.forename: L M
authors.initials: LM
authors.lastname: Riesenbeck
authors.forename: S
authors.initials: S
authors.lastname: Bierer
authors.forename: I
authors.initials: I
authors.lastname: Hoffmeister
authors.forename: T
authors.initials: T
authors.lastname: Köpke
authors.forename: P
authors.initials: P
authors.lastname: Papavassilis
authors.forename: L
authors.initials: L
authors.lastname: Hertle
authors.forename: B
authors.initials: B
authors.lastname: Thielen
authors.forename: E
authors.initials: E
authors.lastname: Herrmann
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001557:Benzenesulfonates / Q000009:adverse effects / Q000627:therapeutic use*; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000401:mortality; D005260:Female; D006801:Humans; D007037:Hypothyroidism / Q000097:blood / Q000139:chemically induced / Q000175:diagnosis*; D007211:Indoles / Q000009:adverse effects / Q000627:therapeutic use*; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009536:Niacinamide / Q000031:analogs & derivatives; D010671:Phenylurea Compounds; D011379:Prognosis; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D011725:Pyridines / Q000009:adverse effects / Q000627:therapeutic use*; D011758:Pyrroles / Q000009:adverse effects / Q000627:therapeutic use*; D012189:Retrospective Studies; D000077157:Sorafenib; D000077210:Sunitinib; D015996:Survival Rate; D013972:Thyrotropin / Q000097:blood; D013974:Thyroxine / Q000097:blood; D016896:Treatment Outcome; D014284:Triiodothyronine / Q000097:blood
chemical_list: D000970:Antineoplastic Agents; D001557:Benzenesulfonates; D007211:Indoles; D010671:Phenylurea Compounds; D011725:Pyridines; D011758:Pyrroles; D014284:Triiodothyronine; D009536:Niacinamide; D013972:Thyrotropin; D000077157:Sorafenib; D011505:Protein-Tyrosine Kinases; D013974:Thyroxine; D000077210:Sunitinib