Park Se Jun, Shin Kabsoo, Kim Hyunho, Park Hyung Soon, Hong Tae Ho, Kim In-Ho, Lee MyungAh
Division of Medical Oncology, Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, South Korea.
Cancer Research Institute, College of Medicine, The Catholic University of Korea, Seoul, South Korea.
Ther Adv Med Oncol. 2025 May 1;17:17588359251335879. doi: 10.1177/17588359251335879. eCollection 2025.
The prognosis for patients with advanced biliary tract cancer (BTC) who have not responded to gemcitabine and cisplatin (GP)-based therapy is dismal. Fluorouracil (5-FU)-based chemotherapy could be considered for those patients who are refractory to GP-based treatments. Our study aimed to evaluate the real-world efficacy and safety of 5-FU-based chemotherapy for BTC patients who had progressed after gemcitabine-based treatment.
This study analyzed patients from Seoul St. Mary's Hospital and St. Vincent's Hospital with advanced BTC who had previously failed treatment with GP-based chemotherapy. From June 2020 and May 2024, these patients received 5-FU-based chemotherapy as a second-line treatment. The 5-FU-based systemic treatments encompassed 5-FU, leucovorin, and oxaliplatin (FOLFOX); 5-FU, leucovorin, and liposomal irinotecan (Nal-IRI/FL); and 5-FU, leucovorin, irinotecan, and oxaliplatin (FOLFIRINOX). Our investigation focused on evaluating the survival outcomes and safety profiles of each regimen within this cohort.
In our analysis of 147 patients, the primary tumor sites were distributed with 56 (38.1%) having intrahepatic cholangiocarcinoma, 51 (34.7%) with extrahepatic cholangiocarcinoma, and 40 (27.2%) with gallbladder cancer. Regarding the 5-FU-based regimens, 57 patients (38.8%) were treated with FOLFOX, 56 (38.1%) with Nal-IRI/FL, and 34 (23.1%) with FOLFIRINOX. The median progression-free survival (PFS) and overall survival (OS) were 2.3 months (95% confidence interval (CI), 2.0-2.6) and 4.8 months (95% CI, 3.8-5.8), respectively. Poor performance status and higher histologic grade were associated with worse PFS and OS, while female gender and prior surgery were linked to improved OS. FOLFOX and Nal-IRI/FL demonstrated comparable efficacy, with a median OS of 5.4 months (95% CI, 3.5-7.3) for FOLFOX and 4.7 months (95% CI, 2.6-6.9) for Nal-IRI/FL, and no significant differences were observed across subgroups. Grade 3 or higher neutropenia and biliary events were less frequent with FOLFOX, which also showed a lower incidence of adverse events and higher relative dose intensity than Nal-IRI/FL or FOLFIRINOX.
In patients with advanced BTC who failed GP treatment, the FOLFOX regimen demonstrated comparable efficacy, and a more favorable safety profile compared to other 5-FU-based treatments. Given its favorable toxicity profile in a real-world setting, FOLFOX should be considered a standard second-line treatment option.
对吉西他滨和顺铂（GP）为基础的治疗无反应的晚期胆管癌（BTC）患者预后不佳。对于对基于GP治疗难治的患者，可考虑基于氟尿嘧啶（5-FU）的化疗。我们的研究旨在评估基于5-FU的化疗对吉西他滨为基础的治疗后进展的BTC患者的真实疗效和安全性。
本研究分析了来自首尔圣母医院和圣文森特医院的晚期BTC患者，这些患者先前接受基于GP的化疗失败。从2020年6月至2024年5月，这些患者接受基于5-FU的化疗作为二线治疗。基于5-FU的全身治疗包括5-FU、亚叶酸钙和奥沙利铂（FOLFOX）；5-FU、亚叶酸钙和脂质体伊立替康（Nal-IRI/FL）；以及5-FU、亚叶酸钙、伊立替康和奥沙利铂（FOLFIRINOX）。我们的研究重点是评估该队列中每种方案的生存结果和安全性。
在我们对147例患者的分析中，原发肿瘤部位分布为肝内胆管癌56例（38.1%），肝外胆管癌51例（34.7%），胆囊癌40例（27.2%）。对于基于5-FU的方案，57例患者（38.8%）接受FOLFOX治疗，56例（38.1%）接受Nal-IRI/FL治疗，34例（23.1%）接受FOLFIRINOX治疗。中位无进展生存期（PFS）和总生存期（OS）分别为2.3个月（95%置信区间（CI），2.0-2.6）和4.8个月（95%CI，3.8-5.8）。体能状态差和组织学分级高与较差的PFS和OS相关，而女性性别和既往手术与改善的OS相关。FOLFOX和Nal-IRI/FL显示出相当的疗效，FOLFOX的中位OS为5.4个月（95%CI，3.5-7.3），Nal-IRI/FL为4.7个月（95%CI，2.6-6.9），各亚组间未观察到显著差异。FOLFOX的3级或更高中性粒细胞减少和胆系事件较少，其不良事件发生率也低于Nal-IRI/FL或FOLFIRINOX，相对剂量强度更高。
在GP治疗失败的晚期BTC患者中，FOLFOX方案显示出与其他基于5-FU的治疗相当的疗效，且安全性更佳。鉴于其在真实世界中的良好毒性特征，FOLFOX应被视为标准的二线治疗选择。
