Phase II placebo-controlled randomized discontinuation trial of sorafnib in patients with metastatic renal cell carcinoma
Phase II placebo-controlled randomized discontinuation trial of sorafnib in patients with metastatic renal cell carcinoma
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DOI：
10.1200/jco.2005.03.6723
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发表时间：
2006-06-01
影响因子：
45.3
通讯作者：
O'Dwyer, Peter J.
中科院分区：
文献类型：
--
作者：
Ratain, Mark J.;Eisen, Tim;O'Dwyer, Peter J.
目的：这项II期随机停药试验评价了针对肿瘤和血管系统的口服多激酶抑制剂索拉非尼(BAY 43-9006)对转移性肾癌患者肿瘤生长的影响。12周后，二维肿瘤测量值变化小于基线的25%的患者被随机分配到索拉非尼或安慰剂治疗另外12周；肿瘤缩小25%的患者继续接受开放标签索拉非尼治疗；肿瘤增长25%的患者停止治疗。主要终点是随机分配的患者在开始服用索拉非尼24周后保持无进展的百分比。结果在磨合期接受治疗的202名患者中，73名患者的肿瘤缩小率为25%。将65名12周后病情稳定的患者随机分为索拉非尼组(n=32)和安慰剂组(n=33)。24周后，接受索拉非尼治疗的患者有50%没有进展，而接受安慰剂治疗的患者只有18%(P=0.0077)。随机分组的中位无进展生存期(PFS)索拉非尼组(24周)显著长于安慰剂组(6周；P=.0087)。整个肾癌人群(n=202)的中位数总体无症状生存时间为29周。在服用安慰剂的28名病情恶化的患者中，索拉非尼再次接受治疗；这些患者继续服用索拉非尼，直到病情进一步恶化，中位数为24周。常见不良反应为皮疹/脱皮、手足皮肤反应、乏力，9%的患者停止治疗，无1例中毒死亡。结论索拉非尼对转移性肾细胞癌具有显著的稳病作用，可耐受长期日常治疗。
Purpose This phase II randomized discontinuation trial evaluated the effects of sorafenib (BAY 43-9006), an oral multikinase inhibitor targeting the tumor and vasculature, on tumor growth in patients with metastatic renal cell carcinoma.Patients and Methods Patients initially received oral sorafenib 400 mg twice daily during the initial run-in period. After 12 weeks, patients with changes in bidimensional tumor measurements that were less than 25% from baseline were randomly assigned to sorafenib or placebo for an additional 12 weeks; patients with >= 25% tumor shrinkage continued open-label sorafenib; patients with 25% tumor growth discontinued treatment. The primary end point was the percentage of randomly assigned patients remaining progression free at 24 weeks after the initiation of sorafenib.Results Of 202 patients treated during the run-in period, 73 patients had tumor shrinkage of >= 25%. Sixty-five patients with stable disease at 12 weeks were randomly assigned to sorafenib (n = 32) or placebo (n = 33). At 24 weeks, 50% of the sorafenib-treated patients were progression free versus 18% of the placebo-treated patients (P = .0077). Median progression-free survival (PFS) from randomization was significantly longer with sorafenib (24 weeks) than placebo (6 weeks; P = .0087). Median overall PFS was 29 weeks for the entire renal cell carcinoma population (n = 202). Sorafenib was readministered in 28 patients whose disease progressed on placebo; these patients continued on sorafenib until further progression, for a median of 24 weeks. Common adverse events were skin rash/desquamation, hand-foot skin reaction, and fatigue; 9% of patients discontinued therapy, and no patients died from toxicity.Conclusion Sorafenib has significant disease-stabilizing activity in metastatic renal cell carcinoma and is tolerable with chronic daily therapy.