Background & objectives: Gallbladder (GBC) is an aggressive form of cancer and most patients present with advanced unresectable disease due to lack of early signs and symptoms. This retrospective study was conducted to present the treatment outcomes with three lines of chemotherapies in a subset of patients with advanced, unresectable GBC with the primary objective to determine the response rates with nab-paclitaxel as the third-line chemotherapy after failure of the first-line gemcitabine and platinum and the second-line FOLFOX-4 (oxaliplatin, leucovorin and 5-FU) therapy. Another objective was to evaluate the toxicity, progression-free survival (PFS) and overall survival (OS).
Methods: Treatment-naive patients with histologically proven inoperable GBC treated with gemcitabine/platinum, FOLFOX-4 and nab-paclitaxel as the first-, second- and third-line chemotherapy were included in this study. The dose of gemcitabine and cisplatin or carboplatin was 1 g/m^[2] on days 1 and 8 and 75 mg/m^[2] (or target AUC of 5) on day 1, in a 21-day cycle. FOLFOX-4 was administered every two weeks and nab-paclitaxel was administered as 125 mg/m^[2] on days 1, 8 and 15 in a 28-day cycle.
Results: There were eight men and 13 women with a median age of 57 yr who received nab-paclitaxel therapy. The overall response rate of the first-, second- and third-line chemotherapy was 61.9, 57.1 and 52.4 per cent, respectively. The median PFS for the gemcitabine/platinum, FOLFOX-4 and nab-paclitaxel therapy was 5.5, 5.4 and 2.9 months, respectively. The median OS with three lines of therapies was 14.0 months. Common Terminology Criteria (CTC) grade 3 or 4 haematological toxicities were observed in 28.6, 38.1 and 23.8 per cent of patients on gemcitabine/platinum, FOLFOX-4 and nab-paclitaxel therapy, respectively.
Interpretation & conclusions: Our study suggests the clinical benefit of nab-paclitaxel chemotherapy in prolonging OS in a selected subgroup of advanced, unresectable GBC patients after failure of the first-line gemcitabine and platinum and the second-line FOLFOX-4 therapy.

中文翻译：

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Nab-紫杉醇：晚期不可切除胆囊癌患者的有效三线化疗

背景和目标：胆囊 (GBC) 是一种侵袭性癌症，大多数患者由于缺乏早期体征和症状而出现无法切除的晚期疾病。这项回顾性研究旨在介绍三线化疗对部分晚期不可切除 GBC 患者的治疗结果，主要目的是确定白蛋白结合型紫杉醇作为一线化疗失败后三线化疗的反应率。一线吉西他滨和铂以及二线FOLFOX-4（奥沙利铂、亚叶酸和5-FU）治疗。另一个目标是评估毒性、无进展生存期 (PFS) 和总生存期 (OS)。
方法：本研究纳入了接受吉西他滨/铂、FOLFOX-4 和白蛋白结合型紫杉醇作为一线、二线和三线化疗的组织学证实无法手术的 GBC 的初治患者。吉西他滨和顺铂或卡铂的剂量在第 1天和第 8 天为 1 g/m ^{[2] ，在第 1 天为 75 mg/m [2]}（或目标 AUC 为 5），以 21 天为一个周期。FOLFOX-4 每两周给药一次，白蛋白结合型紫杉醇在第 1、8 和 15 天以 125 mg/m ^{[2]的剂量给药，周期为 28 天。}
结果：有 8 名男性和 13 名女性接受了白蛋白结合型紫杉醇治疗，中位年龄为 57 岁。一线、二线和三线化疗的总体反应率分别为 61.9%、57.1% 和 52.4%。吉西他滨/铂、FOLFOX-4 和白蛋白结合型紫杉醇治疗的中位 PFS 分别为 5.5、5.4 和 2.9 个月。三线治疗的中位 OS 为 14.0 个月。在接受吉西他滨/铂、FOLFOX-4 和白蛋白结合型紫杉醇治疗的患者中，分别有 28.6%、38.1% 和 23.8% 的患者出现通用术语标准 (CTC) 3 级或 4 级血液学毒性。
解释和结论：我们的研究表明，在一线吉西他滨和铂类药物以及二线 FOLFOX-4 治疗失败后，白蛋白结合型紫杉醇化疗在延长选定的晚期、不可切除 GBC 患者亚组的 OS 方面具有临床益处。