Department of Urology, University of Münster, Albert-Schweitzer Strasse 33, 48149, Münster, Germany.
World J Urol. 2011 Dec;29(6):807-13. doi: 10.1007/s00345-010-0627-2. Epub 2010 Dec 14.
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).
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.
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.
The development of hypothyroidism during treatment might be useful as a predictor of PFS for mRCC patients undergoing treatment with targeted agents.
研究接受酪氨酸激酶抑制剂（TKI）索拉非尼（So）或舒尼替尼（Su）治疗的转移性肾细胞癌（mRCC）患者的预后标志物。
对 2006 年至 2009 年在我院接受治疗的 83 例 mRCC 患者进行前瞻性评估。研究了临床和实验室参数以及与治疗相关的不良反应。亚临床甲状腺功能减退症的特点是血清促甲状腺激素（TSH）高于正常上限，而总三碘甲状腺原氨酸（T3）和甲状腺素（T4）均在正常范围内。临床甲状腺功能减退症定义为血清 T3 和 T4 水平降低，同时 TSH 水平升高。
31 例（37.3%）患者接受 So 治疗，52 例（62.7%）患者接受 Su 治疗。单因素分析显示，ECOG 状态（P < 0.0001）、MSKCC 标准（P = 0.003）和治疗反应（P < 0.0001）与无进展生存期（PFS）相关。在 66 例可评估的患者中，有 21 例（31.8%）在治疗期间发生甲状腺功能减退症。其中，8/21（38.1%）例患者接受 So 治疗，13/21（61.9%）例患者接受 Su 治疗。该亚组的反应率为 49.2%。甲状腺功能减退症与较长的 PFS 相关（16.0 ± 0.8 个月比 6.0 ± 0.8 个月，P = 0.032）。大多数患者（16/21（76.2%））在治疗的前 4 周内出现异常 TSH 值。用左甲状腺素进行激素替代治疗对生存没有影响。多因素分析显示，只有 ECOG 状态（ECOG 0/1 比 ECOG 2，P = 0.018）和甲状腺功能减退症（P = 0.01）是独立的预后参数。
在接受靶向药物治疗的 mRCC 患者中，治疗期间发生甲状腺功能减退症可能是预测 PFS 的有用指标。
