A phase I/II study of nedaplatin and 5-fluorouracil with concurrent radiotherapy in patients with esophageal cancer
A phase I/II study of nedaplatin and 5-fluorouracil with concurrent radiotherapy in patients with esophageal cancer
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DOI：
10.1007/s00280-006-0193-x
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发表时间：
2006-02
影响因子：
3
通讯作者：
Y. Sato;T. Takayama;T. Sagawa;T. Okamoto;K. Miyanishi;Tsutomu Sato;Hironobu Araki;S. Iyama;S. Abe;K. Murase;R. Takimoto;H. Nagakura;M. Hareyama;J. Kato;Y. Niitsu
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文献类型：
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作者：
Y. Sato;T. Takayama;T. Sagawa;T. Okamoto;K. Miyanishi;Tsutomu Sato;Hironobu Araki;S. Iyama;S. Abe;K. Murase;R. Takimoto;H. Nagakura;M. Hareyama;J. Kato;Y. Niitsu
目的：目的探讨奈达铂联合5-FU和大剂量放疗治疗食管癌的推荐剂量。II期试验的目的是确定疗效并进一步确定副作用特征。方法：26例临床I期至IVA期食管鳞状细胞癌患者接受了固定剂量氟尿嘧啶的非手术治疗（第1-5天和第8-12天连续静脉输注400 mg/m2）加递增剂量奈达铂第1、8天分别给予40 mg/m2、50 mg/m2或60 mg/m2剂量的第1、2、3级放疗，每3周重复2次，同时给予60戈伊的放疗。在研究的I期，12名患者在每个剂量水平3至6名患者的连续队列中接受治疗。在水平3时达到最大耐受剂量，出现2例4级中性粒细胞减少症和1例4级血小板减少症。因此，推荐的给药方案为水平2。在RD 2级治疗的20例患者中，包括RD I期部分的6例患者，8/20例患者（40%）发生3-4级中性粒细胞减少症，5例患者（25. 0%）发生3 -4级血小板减少症，4例患者（20. 0%）发生3级贫血，4例患者（20. 0%）发生3-4级食管炎。其他毒副反应相对较轻，一般为2级或2级以下。26例患者（总有效率为88.5%）有客观反应，其中11例（42.3%）完全缓解。1年和3年生存率分别为65.1%和37.2%，中位生存时间为21.2 month.Conclusions：奈达铂和5-FU联合放疗是一种可行的方案，显示出良好的抗肿瘤活性，在食管癌患者中具有可接受的安全性。
Purpose: To determine the recommended dose (RD) of cis-diammine-glycolatoplatinum (nedaplatin) when given concurrently with 5-FU and high dose radiation therapy in the treatment of esophageal cancer. The purpose of the phase II trial is to determine efficacy and further define the side effect profile.Methods: Twenty-six patients with clinical stage I to IVA squamous cell carcinoma of the esophagus were enrolled in a non-surgical treatment comprised of a fixed dose of fluorouracil (400 mg/m2administered as continuous intravenous infusion on days 1–5 and days 8–12) plus escalating doses of nedaplatin (40 mg/m2in level 1, 50 mg/m2in level 2, or 60 mg/m2in level 3 on days 1 and 8), repeated twice every 3 weeks with concurrent radiotherapy (60 Gy).Results: Between July 1998 and February 2004, a total of 26 patients entered this trial, all of whom were considered evaluable for toxicity assessment. In phase I of the study, 12 patients were treated in sequential cohorts of three to six patients per dose level. The maximum tolerated dose was reached at level 3 with two grade 4 neutropenia and one grade 4 thrombocytopenia. Thus, the recommended dosing schedule is level 2. Of the 20 patients treated at the RD level 2, including 6 patients of the RD phase I portion, 8 out of 20 patients (40%) had grade 3–4 neutropenia, 5 patients (25.0%) had grade 3–4 thrombocytopenia, 4 patients (20.0%) had grade 3 anemia and 4 patients (20.0%) had grade 3–4 esophagitis. Other toxicities were relatively mild and usually of grade 2 or less. Objective responses were noted in the 26 patients (overall response rate, 88.5%) including 11 (42.3%) complete remissions. The 1- and 3-year survival rates were 65.1 and 37.2%, respectively, with a median survival time of 21.2 months.Conclusions: The combination of nedaplatin and 5-FU with radiation is a feasible regimen that shows promising antitumor activity with an acceptable safety profile in patients with esophageal cancer.