Pooled Analysis of Phase II Trials Evaluating Weekly or Conventional Cisplatin as First-Line Therapy for Advanced Urothelial Carcinoma
Pooled Analysis of Phase II Trials Evaluating Weekly or Conventional Cisplatin as First-Line Therapy for Advanced Urothelial Carcinoma
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DOI：
10.1016/j.clgc.2012.12.007
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发表时间：
2013-09-01
影响因子：
3.2
通讯作者：
Sonpavde, Guru
中科院分区：
文献类型：
--
作者：
Maughan, Benjamin L.;Agarwal, Neeraj;Sonpavde, Guru
在 II 期试验的汇总分析中，吉西他滨联合第 1 天顺铂 (GC) 或每周顺铂 (wGC) 在晚期尿路上皮癌中产生了相似的结果和毒性。考虑到 wGC 在肾功能不全患者中的可行性，GC 和 wGC 的前瞻性比较可能会促进广泛的化疗骨干，并加速与生物制剂联合的开发。背景：每 3-4 周一次吉西他滨联合 GC 被认为是晚期尿路上皮癌 (UC) 的常规一线化疗。每周分次剂量顺铂联合 wGC 可能毒性较小且具有相似的活性，但尚未与 GC 进行比较。我们汇总了已发表的 GC 和 wGC 的 II 期试验，以比较疗效和安全性。患者和方法：确定了两项 wGC 试验和 3 项 GC 试验。由于数据并非来自随机试验，因此未对 GC 和 wGC 进行正式比较，并计算了反应率和≥(3) 级毒性的准确 95% 准二项式置信区间 (CI)。结果：95% CI 重叠，表明 wGC 和 GC 一致。 GC 和 wGC 之间的缓解率和≥ 3 级毒性没有明显差异。结论：在 II 期试验的假设生成汇总分析中，吉西他滨联合第 1 天顺铂和 wGC 在晚期 UC 中产生相似的反应和≥3 级毒性。考虑到分次顺铂的肾毒性可能较低，可能有必要对符合顺铂资格和不符合顺铂资格的患者进行 wGC 前瞻性评估，以开发单一化疗模板，以便在广大患者群体中开发与生物制剂的组合。 (C) 2013 Elsevier Inc. 保留所有权利。
In a pooled analysis of phase II trials, gemcitabine combined with day 1 cisplatin (GC) or weekly cisplatin (wGC) yielded similar outcomes and toxicities in advanced urothelial carcinoma. Considering the feasibility of wGC in patients with renal dysfunction, a prospective comparison of GC and wGC might facilitate a broad chemotherapy backbone and accelerate the development of combinations with biological agents.Background: Weekly gemcitabine with GC every 3-4 weeks is considered conventional first-line chemotherapy for advanced urothelial carcinoma (UC). Weekly split-dose cisplatin with wGC might be less toxic and have similar activity, but has not been compared with GC. We pooled published phase II trials of GC and wGC to compare efficacy and safety. Patients and Methods: Two trials of wGC and 3 trials of GC were identified. Because the data were not derived from randomized trials, GC and wGC were not formally compared, and exact 95% quasi-binomial confidence intervals (CI), for response rates and grade >=(3) toxicities were calculated. Results: The 95% CI overlapped, suggesting agreement between wGC and GC. No clear difference in response rates and grade >= 3 toxicities between GC and wGC were observed. Conclusion: Gemcitabine combined with day 1 cisplatin and wGC yielded similar responses and grade >= 3 toxicities in advanced UC in a hypothesis-generating pooled analysis of phase II trials. Considering the probable lower nephrotoxicity of fractionated cisplatin, prospective evaluation of wGC might be warranted across cisplatin-eligible and -ineligible patients to develop a single chemotherapy template for the development of combinations with biological agents in a broad population of patients. (C) 2013 Elsevier Inc. All rights reserved.