拓扑替康口服与静脉剂型二线治疗敏感复发小细胞肺癌的对比研究

Comparison between oral and intravenous topotecan as second-line treatment of relapsed sensitive small cell lung cancer

目的 :系统评价拓扑替康不同剂型在化疗敏感复发小细胞肺癌治疗中的疗效及不良反应。方法 :76例敏感复发小细胞肺癌患者,根据给药方式不同分为2组。口服组37例,每天口服拓扑替康(2.3 mg/m^2),连续5 d;静脉组39例,每天静脉滴注拓扑替康1.5 mg/m^2,连续5 d;21 d为1个周期。有72例患者完成2~6个周期,每2个周期评价1次疗效。主要观察指标为客观缓解率、疾病控制率、无进展生存时间、总生存时间和不良反应。结果 :口服组与静脉组的客观缓解率分别为22.8%和21.6%,疾病控制率分别为71.4%和75.7%,2组差异均无统计学意义(P值均>0.05);2组患者的中位无进展生存时间分别为12和10周,差异无统计学意义(P=0.867);中位总生存时间分别为21和19周,差异无统计学意义(P=0.876)。2组的不良反应均主要为骨髓抑制,口服组3~4度中性粒细胞减少症的发生率为5.4%,明显低于静脉组的21.3%,差异具有统计学意义(P=0.029);口服组血小板下降的发生率为2.7%,低于静脉组的7.7%,但两者的差异无统计学意义(P>0.05);贫血率口服组低于静脉组,2组均未出现3~4度的贫血反应。2组患者非血液学毒性主要是恶心、呕吐、乏力、发热和脱发等,组间差异均无统计学意义(P值均>0.05)。结论 :对于经过一线化疗的敏感型复发小细胞肺癌患者,拓扑替康作为二线用药,口服制剂与静脉制剂疗效相当,但口服制剂的骨髓抑制的发生率更低,应用更方便。

Objective：To evaluate the safety and adverse reactions of different dosage forms of topotecan in the treatment of sensitive recurrent small cell lung cancer（SCLC）.Methods：All of 76 patients with sensitive recurrent SCLC were randomly divided into two groups according to the different strategies of topotecan administration.The oral administration group of 37 cases were treated with oral topotecan（2.3mg·m^-2·d^-1for 5 days）,while the intravenous administration group of 39 cases were treated with intravenously injected topotecan（1.5 mg·m^-2·d^-1for 5 d）.The time of every treatment cycle was 21 days,and there were 72 patients completed 2 to 6 cycles.The efficacy was evaluated per 2 cycles.The main endpoints were objective response rate,disease control rate,progression-free survival,overall survival and adverse reactions.Results：The objective response rates in the oral administration group and intravenous administration group were 22.8%and 21.6%,and the disease control rates were 71.4%and 75.7%,respectively;there was no statistically significant difference between two groups（both P〉0.05）.The median progression-free survival time in the two groups were 12 and 10 weeks,respectively;the difference was not statistically significant（P = 0.867）.The median overall survival time in the two groups were 21 and 19 weeks,respectively;there was no statistic difference（P = 0.876）.The main adverse reaction of the two groups was hematology toxicity.The incidence rate of grade 3/4 neutropenia in oral administration group was lower than that in intravenous administration group（5.4%vs 21.3%）,and the difference was statistically significant（P = 0.029）.The incidence rate of grade 3/4 thrombocytopenia in oral administration group was lower than that in intravenous administration group（2.7%vs 7.7%）,but the difference was not statistically significant（P〉0.05）.The anemia rate in oral administration group was lower than that in intravenous administration group,and there were no patients with the grade 3/4 of anemia reaction in the two groups.The mainly non-hematology toxicities in the two groups were nausea,vomiting,fatigue,fever and alopecia,and the difference between the two groups was not statistically significant（all P〉0.05）.Conclusion：As a drug for second-line therapy,the oral topotecan has similar efficacy to intravenous topotecan in the patients with sensitive relapsed SCLC after first-line chemotherapy.But the incidence rate of bone marrow suppression in oral administration group is reduced,so the application of oral topotecan is more convenient.