吉西他滨联合顺铂治疗晚期非小细胞肺癌的 II 期临床试验。
Phase II trial of gemcitabine plus cisplatin in patients with advanced non-small cell lung cancer.
机构信息
Department of Chemo-therapy Center, Zhejiang Cancer Hospital, Hangzhou, China.
出版信息
Acta Pharmacol Sin. 2010 Jun;31(6):746-52. doi: 10.1038/aps.2010.50.
AIM
To investigate the pharmacodynamics and pharmacokinetics of gemcitabine (dFdC) administered on d 1 and 5 plus cisplatin administered on d 1 in chemonaive patients with stage IIIB or IV non-small cell lung cancer (NSCLC).
METHODS
In each combination cycle, gemcitabine was administered at a dose of 1250 mg/m(2) as a 30 min intravenous (iv) infusion on d 1 and 5 followed by cisplatin at a dose of 75 mg/m(2) as a 3 h iv infusion on d 1 every 3 weeks. There was an interval of 1 h between the two infusions. Clinical response and toxicity of the regimen were observed. Furthermore, the plasma concentrations of gemcitabine (dFdC) and its metabolite (dFdU) at different time points were detected during the first cycle of infusion. Pharmacokinetic software (PKS) was used to estimate the pharmacokinetic parameters of gemcitabine and its metabolite dFdU.
RESULTS
A total of 28 patients was enrolled in the study. The median age was 54 years (range 27-75 years), and most patients were in good clinical condition. Twenty-seven patients received two or more treatment cycles. The overall clinical response rate was 33.3%. The median overall survival time was 13 months. The estimated median time to tumor progression (TTP) was 6.2 months, and the 1-year survival rate was 55.6%. Toxicities were tolerated. The main toxicity was myelosuppression; 35.7% of patients had grade 3/4 hematologic toxicities and 28.6% had grade 3/4 non-hematologic toxicities, which were commonly gastrointestinal responses. The pharmacokinetic parameters of dFdC and dFdU were not different between pre- and post-administration of gemcitabine on d 1 and 5. dFdU was minimal (0.729+/-0.637 microg/mL) before gemcitabine was infused on d 5, and gemcitabine was not present.
CONCLUSION
The regimen is active and well tolerated in chemonaive patients with advanced NSCLC. After gemcitabine was administered on d 1 and 5, the pharmacokinetic parameters of dFdC and dFdU showed no difference from those before the infusion, and dFdU was minimal before gemcitabine was administered on d 5.
目的
研究吉西他滨（dFdC）于第 1 天和第 5 天给药联合顺铂于第 1 天给药方案在未经化疗的 IIIB 或 IV 期非小细胞肺癌（NSCLC）患者中的药效学和药代动力学。
方法
在每个联合周期中，吉西他滨以 1250mg/m(2)剂量作为 30 分钟静脉内（iv）输注，于第 1 天和第 5 天给药，随后顺铂以 75mg/m(2)剂量作为 3 小时 iv 输注于第 1 天给药，每 3 周一次。两种输注之间有 1 小时的间隔。观察该方案的临床反应和毒性。此外，在第一个输注周期期间检测不同时间点的吉西他滨（dFdC）及其代谢物（dFdU）的血浆浓度。使用药代动力学软件（PKS）来估计吉西他滨及其代谢物 dFdU 的药代动力学参数。
结果
共纳入 28 例患者。中位年龄为 54 岁（范围 27-75 岁），大多数患者临床状况良好。27 例患者接受了两个或更多治疗周期。总体临床缓解率为 33.3%。中位总生存时间为 13 个月。估计中位肿瘤进展时间（TTP）为 6.2 个月，1 年生存率为 55.6%。毒性可耐受。主要毒性为骨髓抑制；35.7%的患者有 3/4 级血液学毒性，28.6%有 3/4 级非血液学毒性，常见的是胃肠道反应。吉西他滨于第 1 天和第 5 天给药前后，dFdC 和 dFdU 的药代动力学参数无差异。dFdU 在吉西他滨于第 5 天输注前很少（0.729+/-0.637 microg/mL），而吉西他滨则不存在。
结论
该方案在未经化疗的晚期 NSCLC 患者中具有活性且可耐受。吉西他滨于第 1 天和第 5 天给药后，dFdC 和 dFdU 的药代动力学参数与输注前无差异，且吉西他滨于第 5 天给药前 dFdU 很少。
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