State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Sun Yat-sen University, Guangzhou, 510060, People's Republic of China.
Research Unit of Precision Diagnosis and Treatment for Gastrointestinal Cancer, Chinese Academy of Medical Sciences, Guangzhou, 510060, People's Republic of China.
Invest New Drugs. 2021 Jun;39(3):836-845. doi: 10.1007/s10637-020-01045-7. Epub 2021 Jan 7.
Background Gemcitabine plus cisplatin is regarded as the standard first-line therapy for patients with advanced biliary tract cancer (BTC); however, no standard chemotherapy has yet been recommended after treatment failure. Modified FOLFIRINOX (mFOLFIRINOX) appears to be a better-tolerated regimen, which leads to improved survival in metastatic pancreatic cancer that has histological and molecular similarities with BTC. We assessed the efficacy and safety of mFOLFIRINOX as salvage therapy in advanced BTC patients who were refractory to previous chemotherapy. Methods A total of 15 consecutive patients with documented unresectable locally advanced or metastatic BCT who received the mFOLFIRINOX regimen were included in the study. Patients were intravenously administrated with oxaliplatin (65 mg/m), leucovorin (400 mg/m), irinotecan (150 mg/m), and continuous infusion of fluorouracil (2400 mg/m) over 46 h. The objective response rates (ORR), disease control rates (DCR), progression-free survival (PFS), overall survival (OS), and adverse events (AEs) were recorded. Results At least three cycles of mFOLFIRINOX regimen were delivered to 15 patients with a median number of 6.0 cycles (IQR 5.5-11.0). The median duration of treatment was 3.8 months (IQR 2.9-8.5). Four patients (26.7%) achieved an ORR, and 12 patients (80.0%) had a DCR. The median PFS and OS were 6.7 months (95%CI 2.3-11.1) and 13.2 months (95%CI 7.3-19.1), respectively. Five patients (33.3%) had treatment-related grade 3/4 AEs. The most common grade 3/4 AE was neutropenia (n = 3, 20.0%), while there was no occurrence of febrile neutropenia. Conclusion Treatment with mFOLFIRINOX has promising efficacy and favorable tolerance as salvage therapy in patients with refractory advanced BCT.
背景 吉西他滨联合顺铂被认为是晚期胆道癌（BTC）患者的标准一线治疗方法；然而，在治疗失败后，尚无标准的化疗推荐。改良 FOLFIRINOX（mFOLFIRINOX）方案似乎耐受性更好，在转移性胰腺癌中可改善生存，而转移性胰腺癌在组织学和分子上与 BTC 相似。我们评估了 mFOLFIRINOX 作为先前化疗耐药的晚期 BTC 患者的挽救治疗的疗效和安全性。
方法 共纳入 15 例经组织学证实无法切除的局部晚期或转移性 BTC 患者，接受 mFOLFIRINOX 方案治疗。患者静脉滴注奥沙利铂（65mg/m）、亚叶酸（400mg/m）、伊立替康（150mg/m）和氟尿嘧啶持续输注（2400mg/m）46 小时。记录客观缓解率（ORR）、疾病控制率（DCR）、无进展生存期（PFS）、总生存期（OS）和不良事件（AE）。
结果 15 例患者至少接受了 3 个周期的 mFOLFIRINOX 方案治疗，中位周期数为 6.0 个周期（IQR 5.5-11.0）。中位治疗时间为 3.8 个月（IQR 2.9-8.5）。4 例患者（26.7%）获得 ORR，12 例患者（80.0%）获得 DCR。中位 PFS 和 OS 分别为 6.7 个月（95%CI 2.3-11.1）和 13.2 个月（95%CI 7.3-19.1）。5 例患者（33.3%）发生与治疗相关的 3/4 级 AE。最常见的 3/4 级 AE 是中性粒细胞减少症（n=3，20.0%），无发热性中性粒细胞减少症发生。
结论 mFOLFIRINOX 作为难治性晚期 BTC 患者的挽救性治疗具有良好的疗效和耐受性。
