CAJ | 학술논문

目的观察局部进展或转移性结直肠癌患者化疗后,氟尿嘧啶(5-Fu)血药浓度与疗效及不良反应之间的关系,探讨其在进一步提高化疗疗效和减少不良反应中的作用.方法 86例不可切除的局部进展或转移性结直肠癌患者中,50例接受FOLFOX4方案(奥沙利铂+亚叶酸钙+氟尿嘧啶)、36例接受FOLFIRI方案(伊立替康+亚叶酸钙+氟尿嘧啶)一线化疗.于每周期5-Fu持续滴注开始后12h,应用高效液相色谱法检测患者的5-Fu血药浓度.按照3个周期血药浓度的平均值,将86例患者分为＜ 25 ng/ml组、25 ～ 35 ng/ml组和＞35 ng/ml组,回顾性分析不同5-Fu血药浓度与化疗疗效和不良反应之间的关系.结果＜25 ng/ml组、25～ 35 ng/ml组和＞35 ng/ml组5-Fu血药浓度分别为(23.48±1.95) ng/ml、(31.47±2.33) ng/ml和(39.89±3.87) ng/ml,差异有统计学意义(P＜0.01).3组的疾病控制率(DCR)分别为61.5％、74.3％和80.0％,中位总生存期(OS)分别为13.0、18.0和17.5个月,中位无进展生存期(PFS)分别为4.5、7.5和8.0个月.与＜25 ng/ml组相比,25～35 ng/ml组和＞35 ng/ml组DCR分别提高了20.8％和30.1％,中位OS分别提高了5.0和4.5个月(P＜0.01),中位PFS分别提高了3.0和3.5个月(P＜0.01).随着5-Fu血药浓度的增高,化疗引起骨髓抑制、黏膜炎和腹泻的发生率增高,程度加重(P值分别为0.02、0.04和0.02).结论晚期结直肠癌患者经过以5-Fu为基础的方案化疗后,5-Fu血药浓度在25～35 mg/L的患者预后较好,骨髓抑制、黏膜炎和腹泻等不良反应的发生率亦较低.
목적 관찰국부진전혹전이성결직장암환자화료후,불뇨밀정(5-Fu)혈약농도여료효급불량반응지간적관계,탐토기재진일보제고화료료효화감소불량반응중적작용.방법 86례불가절제적국부진전혹전이성결직장암환자중,50례접수FOLFOX4방안(오사리박+아협산개+불뇨밀정)、36례접수FOLFIRI방안(이립체강+아협산개+불뇨밀정)일선화료.우매주기5-Fu지속적주개시후12h,응용고효액상색보법검측환자적5-Fu혈약농도.안조3개주기혈약농도적평균치,장86례환자분위＜ 25 ng/ml조、25 ～ 35 ng/ml조화＞35 ng/ml조,회고성분석불동5-Fu혈약농도여화료료효화불량반응지간적관계.결과 ＜25 ng/ml조、25～ 35 ng/ml조화＞35 ng/ml조5-Fu혈약농도분별위(23.48±1.95) ng/ml、(31.47±2.33) ng/ml화(39.89±3.87) ng/ml,차이유통계학의의(P＜0.01).3조적질병공제솔(DCR)분별위61.5％、74.3％화80.0％,중위총생존기(OS)분별위13.0、18.0화17.5개월,중위무진전생존기(PFS)분별위4.5、7.5화8.0개월.여＜25 ng/ml조상비,25～35 ng/ml조화＞35 ng/ml조DCR분별제고료20.8％화30.1％,중위OS분별제고료5.0화4.5개월(P＜0.01),중위PFS분별제고료3.0화3.5개월(P＜0.01).수착5-Fu혈약농도적증고,화료인기골수억제、점막염화복사적발생솔증고,정도가중(P치분별위0.02、0.04화0.02).결론 만기결직장암환자경과이5-Fu위기출적방안화료후,5-Fu혈약농도재25～35 mg/L적환자예후교호,골수억제、점막염화복사등불량반응적발생솔역교저.
Objective To investigate the relationship between serum concentration of fluorouracil and therapeutic efficacy as well as adverse reactions in patients with unresectable locally advanced or measurable metastatic colorectal cancer,and to analyze its role in further improving therapeutic efficacy and reducing adverse reactions of fluorouracil-based chemotherapy.Methods Eighty-six patients were randomly assigned into three groups according to the average plasma concentration of fluorouracil after three cycles of chemotherapy with the initial regimen of two weeks FOLFOX-4 ( oxaliplatin + leucovorin + fluorouracil) or FOLFIRI (irinotecan + leucovorin + fluorouracil):group 1 (plasma concentration of fluorouracil ＜25 ng/ml),group 2 (25-35 ng/ml) and group 3 ( ＞35 ng/ml).The blood samples were taken at 12 h after continuous infusion of fluorouracil in each cycle and the plasma concentration of fluorouracil was detected by high performance liquid chromatography (HPLC) (about 5 am ± 1 h).The relationship between the drug plasma concentration,therapeutic efficacy and adverse reactions in different fluorouracil plasma concentration arms was analyzed retrospectively.Results The average plasma concentrations of fluorouracil of the three groups were (23.48 ± 1.95) ng/ml,(31.47 ± 2.33 ) ng/ml and (39.89 ± 3.87) ng/ml,respectively ( P ＜ 0.01 ).As for therapeutic efficacy,the median OS of the groups 2 and 3 were 18.0 and 17.5 months,significantly higher than that in the group 1 (13.0 months,P＜0.01).The PFS were 4.5,7.5 and 8.0 months,respectively ( P ＜ 0.01 ). In terms of adverse reactions,the incidences of bone marrow suppression,mucositis and diarrhea in the group 3 were significantly higher than that in the first two groups (P =0.02,P =0.04 and P =0.02).Conclusions The patients with local advanced and metastatic colorectal cancer,receiving fluorouracil-based chemotherapy,and with an average plasma concentration of fluorouracil between 25-35 mg/L have a better prognosis,and lower incidence of adverse reactions such as bone marrow suppression,mucositis and diarrhea.