Department of Internal Medicine, Medicine Institute.
Department of Solid Tumor Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH, USA.
Ann Oncol. 2010 Aug;21(8):1618-1622. doi: 10.1093/annonc/mdp603. Epub 2010 Jan 20.
Although clinical trials with sunitinib and sorafenib in metastatic renal cell carcinoma (mRCC) have included patients with moderate renal insufficiency (RI), the incidence of renal toxicity induced by their administration as well as the safety of these agents in patients with more severe renal insufficiency has not been extensively reported.
Patients with mRCC treated with vascular endothelial growth factor-targeted therapy with either RI at time of treatment initiation or who developed RI during therapy were identified. RI was defined as serum creatinine (Cr) > or = 1.9 mg/dl or a creatinine clearance (CrCl) < 60 ml/min/1.73 m(2) for >3 months before treatment. Objective outcomes and toxic effects of treatment were also measured.
A total of 39 patients were identified: 21 patients who initiated therapy with preexisting RI and 18 patients who developed RI during treatment. In patients with RI at the start of therapy, Cr increased in 57%, and 48% of patients required dose reduction. The median time to maximum RI was 6.6 months (range 0.4-19.6 months). In patients who developed RI while receiving therapy, median serum Cr and CrCl at the start of therapy were 1.5 mg/dl (range 1.1-1.8) and 61 ml/min (range 43-105), respectively. Patients experienced a median increase in serum Cr of 0.8 mg/dl (range 0.3-2.8) and a median decrease in CrCl of 25 ml/min (range 8.54-64.76). Overall, 5 patients (24%) achieved a partial response (PR), 13 (62%) had stable disease (SD) and 3 (14%) had progressive disease (PD). Estimated progression-free survival (PFS) was 8.4 months. The most common toxic effects (all grades) were fatigue (81%), hand-foot syndrome (HFS) (52%) and diarrhea (48%). Six patients experienced grade III toxicity (29%), primarily HFS.
Sunitinib and sorafenib can be safely given to patients with renal insufficiency, provided adequate monitoring of renal function. For those patients developing an increase in Cr, dose modifications may be required to allow continuation of therapy. The clinical outcome of patients with baseline renal dysfunction and patients who develop renal dysfunction does not appear to be compromised.
虽然舒尼替尼和索拉非尼治疗转移性肾细胞癌（mRCC）的临床试验纳入了有中度肾功能不全（RI）的患者，但尚未广泛报道其治疗引起的肾毒性发生率以及这些药物在更严重肾功能不全患者中的安全性。
本研究确定了接受血管内皮生长因子靶向治疗的 mRCC 患者，这些患者在治疗开始时即有 RI，或在治疗期间发生 RI。RI 定义为血清肌酐（Cr）>或=1.9mg/dl 或治疗前 3 个月 CrCl<60ml/min/1.73m2。同时还测量了治疗的客观疗效和毒性作用。
共确定了 39 例患者：21 例患者在开始治疗时就有 RI，18 例患者在治疗期间发生 RI。在开始治疗时就有 RI 的患者中，Cr 增加了 57%，48%的患者需要减少剂量。最大 RI 出现的中位时间为 6.6 个月（范围 0.4-19.6 个月）。在接受治疗期间发生 RI 的患者中，治疗开始时的中位血清 Cr 和 CrCl 分别为 1.5mg/dl（范围 1.1-1.8）和 61ml/min（范围 43-105）。患者的血清 Cr 中位数增加了 0.8mg/dl（范围 0.3-2.8），CrCl 中位数下降了 25ml/min（范围 8.54-64.76）。总的来说，5 例患者（24%）达到部分缓解（PR），13 例（62%）病情稳定（SD），3 例（14%）病情进展（PD）。估计无进展生存期（PFS）为 8.4 个月。最常见的毒性作用（所有等级）是疲劳（81%）、手足综合征（HFS）（52%）和腹泻（48%）。6 例患者发生 3 级毒性（29%），主要是 HFS。
在充分监测肾功能的情况下，舒尼替尼和索拉非尼可以安全地用于肾功能不全的患者。对于那些 Cr 升高的患者，可能需要调整剂量以允许继续治疗。基线肾功能不全的患者和发生肾功能不全的患者的临床结局似乎没有受到影响。
