A phase I/II trial of celecoxib with chemotherapy and radiotherapy in the treatment of patients with locally advanced oesophageal cancer
A phase I/II trial of celecoxib with chemotherapy and radiotherapy in the treatment of patients with locally advanced oesophageal cancer
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DOI：
10.1007/s10637-006-9016-5
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发表时间：
2007-04-01
影响因子：
3.4
通讯作者：
Zalcberg, J. R.
中科院分区：
文献类型：
--
作者：
Dawson, S. J.;Michael, M.;Zalcberg, J. R.
背景：该研究的目的是确定塞来昔布联合放化疗（CRT）治疗局部晚期食管癌（OC）的最大耐受剂量（MTD）。方法：5FU （1000 mg/m(2)/天，第1 ~ 4天，第1、5周），顺铂（75 mg/m(2)，第1、29天），放疗（50 Gy， 25次，50.4 Gy， 28次）。塞来昔布在CRT期间每天给予五种剂量之一（200mg / d至600mg / d）。每个剂量分配3至6名患者。结果：由于塞来昔布的外部安全性问题，在试验结束前招募了13名患者。中位随访时间为17个月（95% CI 9 - 39）。最高给药剂量为400mg / d (n=4)，该剂量有一个剂量限制性毒性：3级皮疹。5例（38%）和8例（62%）患者分别为3级非血液学和血液学毒性。未发生4级毒性反应。放射反应率为54% （n=7：全部CR）。6例患者行手术切除，1例病理性CR。中位无进展生存期和总生存期分别为8.8个月（95% CI 5.1 - bbb24.8）和19.6个月（95% CI 7.3 - bbb39）。结论：未达到MTD。该方案是可耐受的，表明塞来昔布可以安全地与CRT一起用于局部晚期OC。
Background: The study's aim was to determine the maximum tolerated dose (MTD) of celecoxib combined with chemoradiotherapy (CRT) for locally advanced oesophageal cancer (OC).Methods: CRT comprised of 5FU (1000 mg/m(2)/day, days 1-4, weeks 1 & 5), cisplatin (75 mg/m(2), days 1 & 29) and radiotherapy (50 Gy in 25 fractions or 50.4 Gy in 28 fractions). Celecoxib was given daily during CRT at one of five doses (200 mg bd to 600 mg bd). Three to six patients were assigned per dose.Results: Thirteen patients were recruited before trial closure due to external safety concerns regarding celecoxib. Median follow up was 17 months (95% CI 9 - > 39). The highest administered dose was 400 mg bd (n=4) with one dose-limiting toxicity at this level: grade 3 rash. Five (38%) and 8(62%) patients had grade 3 non-haematological and haematological toxicities respectively. No grade 4 toxicities occurred. Radiological response rate was 54% (n=7: all CR). Six patients had resection with one pathological CR. Median progression-free and overall survival were 8.8 (95% CI 5.1 - > 24.8) and 19.6 months (95% CI 7.3 - > 39) respectively.Conclusions: A MTD was not reached. The regimen was tolerable, indicating that celecoxib can be safely administered with CRT for locally advanced OC.