Phase I trial of concurrent chemoradiation with weekly nedaplatin in patients with squamous cell carcinoma of the uterine cervix.
Phase I trial of concurrent chemoradiation with weekly nedaplatin in patients with squamous cell carcinoma of the uterine cervix.
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DOI：
10.1016/j.ygyno.2006.06.034
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发表时间：
2007
影响因子：
4.7
通讯作者：
K. Yoshinaga;H. Niikura;Y. Ogawa;K. Nemoto;S. Nagase;T. Takano;K. Ito;N. Yaegashi
中科院分区：
文献类型：
--
作者：
K. Yoshinaga;H. Niikura;Y. Ogawa;K. Nemoto;S. Nagase;T. Takano;K. Ito;N. Yaegashi
目的：本项宫颈癌I期临床试验有三个目的：评价以奈达铂每周一次为特征的同步放化疗方案的毒性;确定奈达铂用于II期同步放化疗试验的推荐剂量;并通过药代动力学研究评价预测奈达铂曲线下面积的公式。子宫颈入组。奈达铂每周给药一次，持续6周。奈达铂的起始剂量为25 mg/m2/周，每个剂量水平计划增加5 mg/m2/周。每个剂量水平入组3例病例。放射治疗采用外照射远距离放射治疗和腔内近距离放射治疗（HDR-RALS）。第二疗程进行药代动力学研究，顺铂25、30、35 mg/m2剂量组各3例安全。然而，在40 mg/m2剂量下，所有3例病例均发生3级中性粒细胞减少症。观察到的曲线下面积值与预测值密切相关，两个曲线下面积值之间的差异在25%以内。所有12例均达到临床完全反应，评价与RECIST.CONCLUSIONSOUR推荐剂量为II期临床试验的同时放化疗与每周奈达铂是35 mg/m2。该公式可以根据曲线下面积预测奈达铂的未结合浓度，误差在25%以内。
OBJECTIVEThis phase I clinical trial for cervical carcinoma had three objectives: to evaluate the toxicity of a concurrent chemoradiation regimen featuring weekly nedaplatin; to determine the recommended dose of nedaplatin for a phase II concurrent chemoradiation trial; and to evaluate the formula for predicting area under the curve data for nedaplatin through pharmacokinetic studies.PATIENTS AND METHODSTwelve patients with locally advanced squamous cell carcinoma of the uterine cervix were enrolled. Nedaplatin was administered once a week for 6 weeks. The starting dose of nedaplatin was 25 mg/m2/week, with increments of 5 mg/m2/week planned for each dose level. Three cases were enrolled at each of the dose levels. Radiation therapy was delivered with both external beam teletherapy and intracavitary brachytherapy with HDR-RALS. Volunteering patients underwent pharmacokinetics studies during the second course.RESULTSNedaplatin at a dose of 25, 30, and 35 mg/m2was safely administered for three cases at each dose level. At a dose of 40 mg/m2, however, all three cases had Grade 3 neutropenia. Observed area under the curve value and predicted value was closely correlated, with differences between the two area under the curve values within 25%. All 12 cases achieved a clinical complete response, as evaluated with RECIST.CONCLUSIONSOur recommended dose for a phase II trial of concurrent chemoradiation with weekly nedaplatin is 35 mg/m2. The formula can predict unbound concentration of nedaplatin based on area under the curve within 25% error.