减量FOLFIRINOX方案挽救性治疗吉西他滨抵抗的晚期胰腺癌:一项Ⅱ期研究

背景与目的奥沙利铂、伊立替康、氟尿嘧啶和亚叶酸的联合化疗方案(FOLFIRINOX)极大提高了晚期胰腺癌患者的生存期。然而,FOLFIRINOX方案作为吉西他滨失败后二线治疗的疗效尚未进行前瞻性的检测。我们研究了减量FOLFIRINOX方案治疗吉西他滨抵抗的晚期胰腺癌患者的可行性和安全性。方法在14家医院进行了这一多中心II期前瞻、开放标签的单臂研究。经组织学确诊为胰腺浸润性导管腺癌、有可测量或可评价的病灶、东部肿瘤协作组体能状况评分0或1分、器官功能良好、年龄19岁或以上的患者符合入组条件。减量FOLFIRINOX方案的组成:奥沙利铂65 mg/m2、伊立替康135 mg/m2和亚叶酸400 mg/m2,第1天静脉注射;5?氟尿嘧啶2000 mg/m2,第1–2天持续静脉输注46 h;每2周重复。主要终点为FOLIFLIOX治疗起始后的无进展生存期。次要终点为客观缓解率、疾病控制率、总生存期、安全性和耐受性。采用Kaplan?Meier法评估了总生存期和无进展生存期。结果我们招募了来自14个中心的39例患者。客观缓解率为10.3%,疾病控制率为64.1%。6个月和1年总生存率分别为59.0%和15.4%。中位无进展生存期和总生存期分别为3.8个月[95%置信区间(confidence interval,CI)=1.5–6.0个月]和8.5个月(95%CI=5.6–11.4个月)。3或4级不良事件为中性粒细胞减少(41%)、恶心(10.3%)、食欲减退(10.3%)、贫血(7.7%)、黏膜炎(7.7%)、肺炎/胸膜融合(5.1%)和乏力(5.1%)。发生1例由感染性休克引起的治疗相关死亡。结论减量FOLFIRINOX方案有望作为二线方案治疗吉西他滨抵抗的胰腺癌。

Attenuated FOLFIRINOX in the salvage treatment of gemcitabine-refractory advanced pancreatic cancer: a phase II study

Background:Combination therapy with oxaliplatin,irinotecan,fluorouracil,and leucovorin(FOLFIRINOX)chemotherapy drastically improves survival of advanced pancreatic cancer patients.However,the efficacy of FOLFIRINOX as a second-line treatment after gemcitabine failure has not been tested prospectively.We investigated the feasibility and safety of attenuated FOLFIRINOX in patients with gemcitabine-refractory advanced pancreatic cancer.Methods:A multicenter phase II prospective open-label,single-arm study was conducted at 14 hospitals.Patients with histologically proven invasive ductal pancreatic adenocarcinoma,a measurable or evaluable lesion,Eastern Cooperative Oncology Group performance status 0 or 1,adequate organ function,and aged 19 years or older were eligible.Attenuated FOLFIRINOX consisted of oxaliplatin 65 mg/m2,irinotecan 135 mg/m2,and leucovorin 400 mg/m2 injected intravenously on day 1 and 5-fluorouracil 2000 mg/m2 continuously infused intravenously over 46 h on days 1-2,repeated every 2 weeks.The primary endpoint was progression-free survival from the initiation of FOLFIRINOX.Secondary endpoints were the objective response rate,disease control rate,overall survival,safety,and tolerability.We estimated overall survival and progression-free survival using the Kaplan-Meier methods.Results:We enrolled 39 patients from 14 institutions.The objective response rate was 10.3%,while the disease control rate was 64.1%.The 6-month and 1-year overall survival rates were 59.0%and 15.4%,respectively.Median progression-free survival and overall survival were 3.8 months(95%confidence interval[CI]1.5-6.0 months)and 8.5 months(95%CI 5.6-11.4 months),respectively.Grade 3 or 4 adverse events were neutropenia(41.0%),nausea(10.3%),anorexia(10.3%),anemia(7.7%),mucositis(7.7%),pneumonia/pleural effusion(5.1%),and fatigue(5.1%).One treatment-related death attributable to septic shock occurred.Conclusion:Attenuated FOLFIRINOX may be promising as a second-line therapy for gemcitabine-refractory pancre-atic cancer.