Phase II Study of Gemcitabine, Carboplatin, and Bevacizumab in Patients With Advanced Unresectable or Metastatic Urothelial Cancer
Phase II Study of Gemcitabine, Carboplatin, and Bevacizumab in Patients With Advanced Unresectable or Metastatic Urothelial Cancer
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DOI：
10.1200/jco.2012.42.5215
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发表时间：
2013-02-20
影响因子：
45.3
通讯作者：
Bajorin, Dean F.
中科院分区：
文献类型：
--
作者：
Balar, Arjun V.;Apolo, Andrea B.;Bajorin, Dean F.
目的虽然吉西他滨和卡铂 (GCa) 是不适合顺铂治疗的晚期尿路上皮癌 (UC) 患者的标准选择，但结果仍然不佳。该试验评估了贝伐珠单抗联合 GCa 在晚期 UC 中的疗效和安全性。 患者和方法 卡诺夫斯基体力状态为 60% 至 70%、肌酐清除率低于 60 mL/min、内脏转移或孤立肾的患者符合资格，并接受贝伐珠单抗 10 mg/kg 的导入剂量，随后 2 周后每天接受吉西他滨 1,000 mg/m(2)。 1和8，卡铂[浓度-时间]曲线下面积(AUC) 5.0或4.5，贝伐单抗15 mg/kg，第1天每21天一次，共六个周期。达到疾病至少稳定 (SD) 的患者继续每 21 天服用 15 mg/kg 贝伐珠单抗，持续 18 个周期。该研究的结果是，与历史对照相比，中位无进展生存期 (PFS) 提高了 50%。 结果 51 名患者，中位年龄 67 岁（范围：42 至 83 岁）被纳入该研究，并可进行毒性评估。 20 人 (39%) 经历了 3 至 4 级毒性，10 人 (20%) 发生血栓栓塞事件（深静脉血栓或肺栓塞）。其中 4 人接受了一个或更少的周期，剩下 47 人可评估结果。 23 例 (49%) 获得缓解（3 例完全缓解；20 例部分缓解），11 例出现 SD。中位 PFS 为 6.5 个月（95% CI，4.7 至 7.8 个月）；卡铂 AUC 5.0 组的 PFS 更高 (P = .04)。中位总生存期 (OS) 为 13.9 个月。 结论 中位 PFS 4.77 个月的 95% 单侧置信下限未达到预先指定的超过 4.8 个月的 PFS，被认为足以进行进一步研究。中位 OS 高于预期。一项针对符合顺铂治疗条件的患者正在进行的 III 期试验将明确贝伐珠单抗在 UC 中的作用。 J 临床肿瘤杂志 31：724-730。 (C) 2013 年美国临床肿瘤学会
PurposeAlthough gemcitabine and carboplatin (GCa) is a standard option for patients with advanced urothelial cancer (UC) who are ineligible for cisplatin, outcomes remain poor. This trial evaluated the efficacy and safety of bevacizumab with GCa in advanced UC.Patients and MethodsPatients with Karnofsky performance status of 60% to 70%, creatinine clearance less than 60 mL/min, visceral metastasis, or solitary kidney were eligible and received a lead-in dose of bevacizumab 10 mg/kg followed 2 weeks later by gemcitabine 1,000 mg/m(2) on days 1 and 8 and carboplatin at area under the [concentration-time] curve (AUC) 5.0 or 4.5 and bevacizumab 15 mg/kg on day 1 every 21 days for six cycles. Patients achieving at least stable disease (SD) continued bevacizumab 15 mg/kg every 21 days for 18 additional cycles. The study was powered to detect a 50% improvement in median progression-free survival (PFS) over a historical control.ResultsFifty-one patients, median age 67 years (range, 42 to 83 years), were enrolled onto the study and were evaluable for toxicity. Twenty (39%) experienced grade 3 to 4 toxicity, and 10 (20%) had thromboembolic events (deep venous thrombosis or pulmonary embolism). Four received one or fewer cycles leaving 47 evaluable for outcomes. Twenty-three (49%) achieved response (three complete; 20 partial), and 11 had SD. Median PFS was 6.5 months (95% CI, 4.7 to 7.8 months); PFS was greater in the carboplatin AUC 5.0 group (P = .04). Median overall survival (OS) was 13.9 months.ConclusionThe 95% one-sided lower confidence bound of 4.77 months for median PFS did not meet the predesignated PFS of more than 4.8 months considered sufficient for further study. Median OS was greater than expected. An ongoing phase III trial in patients who are eligible for therapy with cisplatin will define the role of bevacizumab in UC. J Clin Oncol 31:724-730. (C) 2013 by American Society of Clinical Oncology