Safety and toxicity analysis of oxaliplatin combined with fluorouracil or as a single agent in patients with previously treated advanced colorectal cancer
Safety and toxicity analysis of oxaliplatin combined with fluorouracil or as a single agent in patients with previously treated advanced colorectal cancer
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DOI：
10.1200/jco.2003.11.045
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发表时间：
2003-08-01
影响因子：
45.3
通讯作者：
Kardinal, CG
中科院分区：
文献类型：
--
作者：
Ramanathan, RK;Clark, JW;Kardinal, CG
目的：在美国和加拿大进行了两项连续的同情使用奥沙利铂的研究，研究对象是5000多名局部晚期或转移性结直肠癌患者，这些患者在至少一次化疗方案后经历了治疗失败。患者和方法：主要关注安全性。在不同的治疗方案中，患者被分配到单药奥沙利铂或奥沙利铂联合氟尿嘧啶（FU）以及加或不加亚叶酸素（IV）。反应数据收集不是试验目的，但在第一队列（1370例患者）中记录了治疗失败时间（TTF）。结果：所有治疗方案耐受性良好，3级或4级血液学毒性总发生率为23.2%，3级或4级治疗相关胃肠道毒性总发生率为26.4%（包括腹泻、呕吐和粘膜炎），3级神经感觉毒性总发生率为3.9%。在第二队列（3,806例患者）中报告了类似的结果，其中的资格标准限制较少。在第一个队列中（其中83%先前接受过伊立替康治疗），中位TTF为14周，并且在联合奥沙利铂和FU合并或不合并LV的五种方案中相似，但单药奥沙利铂组的TTF明显缩短。奥沙利铂的总剂量强度维持在方案规定剂量的85.5%（范围，80.6%至94.3%）（平均36.7 mg/m(2)/周）。结论：这些数据在大量预处理的患者人群中证实，奥沙利铂作为单一药物或与各种基于fu的方案一起用于晚期结直肠癌患者的挽救治疗是安全的。
Purpose: Two consecutive compassionate use studies of oxaliplatin were conducted in the United States and Canada in more than 5,000 patients with locally advanced or metastatic colorectal carcinoma who had experienced treatment failure after at least one prior chemotherapy regimen.Patients and Methods: The main focus was safety. Patients were assigned to treatment with either single-agent oxaliplatin or oxaliplatin in combination with fluorouracil (FU) and with or without leucovorin (IV) in various regimens. Response data collection was not a trial objective, but time to treatment failure (TTF) was recorded in the first cohort (1,370 patients).Results: All treatment regimens were well tolerated, with an overall incidence of grade 3 or 4 hematologic toxicity of 23.2%, grade 3 or 4 treatment-related gastrointestinal toxicity of 26.4% (including diarrhea, vomiting, and mucositis), and grade 3 neurosensory toxicity 3.9%. Similar results were reported in the second cohort (3,806 patients), in which the eligibility criteria were much less restrictive. In the first cohort (in which 83% received prior irinotecan), median TTF was 14 weeks, and was similar for the five regimens combining oxaliplatin and FU with or without LV, but significantly shorter for the single-agent oxaliplatin arm. The overall dose-intensity of oxaliplatin was maintained at 85.5% (range, 80.6% to 94.3%) of that prescribed by protocol (average 36.7 mg/m(2)/wk).Conclusion: These data in a heavily pretreated patient population confirm that oxaliplatin is safe when used as a single agent or with a variety of FU-based regimens as salvage therapy in patients with advanced colorectal cancer.