口服长春瑞滨联合顺铂与静滴长春瑞滨联合顺铂治疗局部晚期或转移的非小细胞肺癌的Ⅱ期临床研究

Effect of Oral Vinorelbine plus Cisplatin in Unresectable Localized or Metastatic Non-Small Cell Lung Cancer (NSCLC): A Report of Stage-Ⅱ Clinical Research

目的:评价口服长春瑞滨联合顺铂和静滴长春瑞滨联合顺铂治疗局部晚期或转移的非小细胞肺癌(NSCLC)的疗效,分析两组患者的无进展生存期、毒性反应以及治疗的安全性。方法:符合入组标准的患者按1:1比例随机分配到口服长春瑞滨联合顺铂的试验组和静滴长春瑞滨联合顺铂的对照组。两组均接受每3周一次的化疗方案。第一疗程中口服长春瑞滨按60mg/m^2,d1、d8,静滴长春瑞滨按25mg/m^2,d1、d8,顺铂均按80mg/m^2,d1。若第一疗程中未出现严重的血液学毒性,第二疗程开始口服长春瑞滨的剂量增加至80mg/m^2,静滴长春瑞滨的剂量增至30mg/m^2。按RECIST标准评价肿瘤缓解情况,按NCI-CTC2.0版本评价毒性分级。结果:中山大学肿瘤防治中心共入组39例合格受试者,试验组19例,对照组20例,两组受试者在性别、年龄、KPS评分、临床分期、组织学类型及吸烟状况是均衡的。采用意向性人群分析方法。试验组和对照组的客观缓解率分别为31.6%和42.1%(P=0.737),临床获益率分别为52.6%和68.4%(P=0.508),中位无进展生存期分别为85天和115天(P=0.705)。两组主要的毒性反应均为中性粒细胞减少症、贫血、胃肠道反应、静脉炎。对照组2级静脉炎发生率明显高于试验组(68.4% vs 21.1%),差异有统计学意义(P=0.008)。其他的不良反应和Ⅲ～Ⅳ度的不良反应两组受试者未观察到有统计学差异。结论:口服长春瑞滨联合顺铂与静滴长春瑞滨联合顺铂的方案在治疗晚期非小细胞肺癌的疗效相似,毒副作用减轻,值得开展更大规模Ⅲ期临床研究进一步评价口服长春瑞滨在亚洲人群中的疗效和毒性。

Objective： To evaluate the efficacy of oral vinorelbine plus cisplattn and Ⅳ vmorelbine plus cisplaatin aavanced non-small-cell lung cancer （NSCLC）, and to appraise the progression-free survival, toxicity, and the safety of both therapeutic applications. Methods： Patients who met the inclusion criteria were randomly （1：1） assigned to the experimental group with oral vinorelbine plus cisplatin （arm A） or the control group with intravenous （IV） vinorelbine plus cisplatin （arm B）. Patients in both the groups were treated with the two therapeutic regimens administered once every 3 weeks. In the first course of treatment, the oral vinorelbine was administrated at a dose of 60 mg/m2 on day 1 and 8, while the Ⅳ vinorelbine was administrated at a dose of 25 mg/m2 on day 1 and 8. In both groups, cisplatin was administrated at the dose Of 80 mg/m2 on day 1. In the second course of treatment, the dose of oral vinorelbine was raised up to 80 mg/m2 and the Ⅳ vinorelbine was raised to 30 mg/m2 for the following cycles, if no severe hematological toxicity was found in these patients. Tumor response rate was appraised according to RECIST criteria, and the toxicity grading was appraised based on NCI-CTC Version 2.0. Results： A total of 39 eligible subjects were enrolled in the Cancer Center of Sun Yat-Sen University, with 19 in the experimental group and 20 controls. Characteristics including gender, age, performance status, clinical stage, histo-types and. smoking status were balanced in the patients of both groups. Data were analyzed in the intentiomto-treat manner. The objective remission rate was 31.6% and 42.1% （P=0.737）, and the clinical benefit rate was 52.6% and 68.4% （P=-0.508） in arm A and B, respectively. The median progression-free survival was 85 and 115 days, respectively, in arm A and B （P=0.705）. Toxic reactions in both groups included neutropenia, anemia, gastrointestinal reactions and phlebitis. Grade-2 phlebitis notably increased in arm B （68.4% vs. 21.0%）, with a statistically significant difference between the two groups （P=-0.008）. No significant differehces were found in the comparison of other adverse effects and grade-Ⅲ -Ⅳ untoward reactions between the subjects of the 2 groups. Conclusion： The efficacy of oral vinorelbine plus cisplatin regimen is similar to that of the IV vinorelbine and cisplatin regimen in the cases with advanced non-small-cell lung cancer （NSCLC）. The hematological toxicity and non-hematological toxicity were lower in the experimental group than in the controls. A larger-scale phase-Ⅲ clinical study is needed to further evaluate the efficacy and toxicity of oral vinorelbine in Asian patients.