多柔比星脂质体联合化疗（CCOP）方案治疗外周 T 细胞淋巴瘤的药效学和药代动力学研究。
Pharmacodynamic and pharmacokinetic study of pegylated liposomal doxorubicin combination (CCOP) chemotherapy in patients with peripheral T-cell lymphomas.
机构信息
Department of Chemotherapy Center, Zhejiang Cancer Hospital, Hangzhou, China.
出版信息
Acta Pharmacol Sin. 2011 Mar;32(3):408-14. doi: 10.1038/aps.2010.217.
AIM
To investigate the pharmacodynamic and pharmacokinetic parameters of pegylated liposomal doxorubicin (PLD) combined with cyclophosphamide, vincristine, and prednisolone in patients with peripheral T-cell lymphomas (PTCL).
METHODS
Seven chemonaive patients and four patients with relapsed peripheral T-cell lymphomas were treated with a CCOP regimen consisting of an intravenous administration of cyclophosphamide (750 mg/m(2)), vincristine (1.4 mg/m(2)), and PLD (30 mg/m(2)) on d 1, as well as an oral administration of prednisolone (60 mg/m(2)) on d 1-5. This regimen was repeated every 3 weeks for six cycles, and the clinical response and toxicity of the regimen were monitored. In addition, the plasma concentration of PLD at different time points was determined before and after treatment. The pharmacokinetics (PKs) software was used to estimate the pharmacokinetic parameters of PLD.
RESULTS
The 11 PTCL patients received 35 treatment cycles. Three of them achieved complete response (CR), two partial response (PR), four stable disease (SD), and two progressive disease (PD). The overall response rate (ORR) was 45.5%, and the CR rate was 27.3%. In the 7 chemonaive patients, three achieved CR, two PR, one SD, and one PD. The ORR was 71.4%, and CR rate was 42.9%. The median follow-up time was 15 months, but 6 out of 11 patients were dead at the time of data analysis. The 1-year overall survival rate was 45.5%, and the median progression-free survival (PFS) rate was 6.5 [95% confidence interval (95% CI) 3.17-19.02] with a survival rate of 11.5 months (95% CI 6.65-16.36). The main toxicity was myelosuppression. Oral mucositis and hand-foot syndrome seldom occurred. The PLD plasma concentration from nine patients ranged from 1.7036 to 9.2207 mg·L(-1) after administration of the CCOP regimen (0-168 h). The pharmacokinetic parameters AUC(0-∞), CL, t(1/2), and V(d) were 910.76 mg/L·h, 0.043 L·h(-1)·m(-2), 68.40 h, and 3.56 L/m(2), respectively.
CONCLUSION
The CCOP regimen was effective and well tolerated in patients with peripheral T-cell lymphomas. The results of the pharmacokinetic parameters showed that PLD had long retention time in blood circulation.
目的
研究多柔比星脂质体（PLD）联合环磷酰胺、长春新碱和泼尼松治疗外周 T 细胞淋巴瘤（PTCL）的药效学和药代动力学参数。
方法
7 例初治 PTCL 患者和 4 例复发的外周 T 细胞淋巴瘤患者采用 CCOP 方案治疗，方案包括静脉注射环磷酰胺（750 mg/m2）、长春新碱（1.4 mg/m2）和 PLD（30 mg/m2），于 d1 给药，同时口服泼尼松（60 mg/m2），于 d1-5 给药。该方案每 3 周重复 6 个周期，并监测方案的临床反应和毒性。此外，在治疗前后不同时间点测定 PLD 的血浆浓度。使用药代动力学（PKs）软件估计 PLD 的药代动力学参数。
结果
11 例 PTCL 患者接受了 35 个治疗周期。其中 3 例达到完全缓解（CR），2 例部分缓解（PR），4 例稳定疾病（SD），2 例进展疾病（PD）。总缓解率（ORR）为 45.5%，CR 率为 27.3%。在 7 例初治患者中，3 例达到 CR，2 例 PR，1 例 SD，1 例 PD。ORR 为 71.4%，CR 率为 42.9%。中位随访时间为 15 个月，但在数据分析时，11 例患者中有 6 例死亡。1 年总生存率为 45.5%，中位无进展生存期（PFS）率为 6.5[95%置信区间（95%CI）为 3.17-19.02]，生存率为 11.5 个月（95%CI 为 6.65-16.36）。主要毒性为骨髓抑制。口腔黏膜炎和手足综合征很少发生。9 例患者在接受 CCOP 方案治疗后（0-168 h）的 PLD 血浆浓度范围为 1.7036-9.2207 mg·L-1。AUC（0-∞）、CL、t（1/2）和 V（d）的药代动力学参数分别为 910.76 mg/L·h、0.043 L·h-1·m-2、68.40 h 和 3.56 L/m2。
结论
CCOP 方案在外周 T 细胞淋巴瘤患者中有效且耐受良好。药代动力学参数结果表明，PLD 在血液中具有较长的滞留时间。
Zotero 插件