Biweekly vinorelbine and gemcitabine:: a phase I dose-finding study in patients with advanced solid tumors
Biweekly vinorelbine and gemcitabine:: a phase I dose-finding study in patients with advanced solid tumors
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DOI：
10.1093/annonc/mdg196
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发表时间：
2003-05-01
影响因子：
50.5
通讯作者：
Colomer, R
中科院分区：
文献类型：
--
作者：
Castellano, D;Hitt, R;Colomer, R
背景：本研究的目的是确定长春瑞滨加吉西他滨组合治疗晚期实体瘤患者的剂量限制毒性 (DLT) 和最大耐受剂量，每两周一次。 患者和方法：本 I 期研究中包括的晚期或难治性实体瘤患者接受长春瑞滨治疗，随后接受吉西他滨治疗。长春瑞滨在 10 分钟内静脉注射，吉西他滨以 10 mg/m(2)/min 的固定剂量输注速度静脉注射。探讨了长春瑞滨/吉西他滨的六种剂量水平：20/2000、25/2500、25/3000、30/3000、30/3500 和 30/2500 mg/m(2)。 结果：本研究纳入 19 名患者。十四名患者接受了化疗和/或放疗的预处理。总共进行了123个周期的化疗。 DLT 在剂量水平 5 (30/3500 mg/m(2)) 时为中性粒细胞减少性发热和 3 级乏力；在剂量水平 4 (30/3000 mg/m(2)) 时，出现 3 级乏力、辐射回忆反应和肺炎。十六名患者进行了疗效评估。 5 名患者获得客观缓解（1 名完全缓解，4 名部分缓解），总缓解率为 31%。 结论：II 期研究的推荐剂量为长春瑞滨 30 mg/m(2) 和吉西他滨 2500 mg/m(2)，每 2 周给药一次。该方案在该剂量下是可行的且耐受性良好，并且在所探索的所有水平上都显示出良好的临床活性。
Background: The purpose of this study was to determine the dose-limiting toxicity (DLT) and maximum tolerated dose of a combination of vinorelbine plus gemcitabine administered on a biweekly schedule in patients with advanced solid tumors.Patients and methods: Patients with advanced or refractory solid tumors included in this phase I study were treated with vinorelbine followed by gemcitabine. Vinorelbine was given intravenously over 10 min, and gemcitabine was given intravenously at an fixed-dose infusion rate of 10 mg/m(2)/min. Six dose levels of vinorelbine/gemcitabine were explored: 20/2000, 25/2500, 25/3000, 30/3000, 30/3500 and 30/2500 mg/m(2).Results: Nineteen patients were included in the study. Fourteen patients were pretreated with chemotherapy and/or radiotherapy. A total of 123 cycles of chemotherapy were administered. DLTs were neutropenic fever and grade 3 asthenia at dose level 5 (30/3500 mg/m(2)); at dose level 4 (30/3000 mg/m(2)) they were grade 3 asthenia, and a radiation-recall reaction and pneumonitis. Sixteen patients were evaluable for efficacy. Five patients had an objective response (one complete response and four partial responses), for an overall response rate of 31%.Conclusions: The recommended dose for phase II study is vinorelbine 30 mg/m(2) and gemcitabine 2500 mg/m(2) administered once every 2 weeks. This regimen is feasible and well-tolerated at this dose, and shows a good clinical activity in all levels explored.