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First evidence for the antitumor activity of nanoliposomal irinotecan with 5-fluorouracil and folinic acid in metastatic biliary tract cancer

纳米脂质体伊立替康与 5-氟尿嘧啶和亚叶酸在转移性胆道癌中的抗肿瘤活性的第一个证据

  • 影响因子:2.95
  • DOI:10.1007/s00280-020-04094-0
  • 作者列表:"Taghizadeh, Hossein","Unseld, Matthias","Schmiderer, Andreas","Djanani, Angela","Wilthoner, Klaus","Buchinger, Dieter","Prager, Gerald W.
  • 发表时间:2020-06-18
Abstract

Background Therapeutic options are limited for advanced, metastatic biliary tract cancer. The pivotal NAPOLI-1 trial demonstrated the superior clinical benefit of nanoliposomal irinotecan (Nal-IRI) in gemcitabine-pretreated patients with metastatic pancreatic ductal adenocarcinoma; however, the antitumor activity of Nal-IRI in biliary tract cancer is unknown. This is the first report describing the efficacy of Nal-IRI in biliary tract cancer. Methods In this multicenter retrospective cohort analysis, we identified patients with metastatic biliary tract adenocarcinoma who were treated with Nal-IRI in combination with 5-fluorouracil and folinic acid following tumor progression under standard therapy at one of the study centers between May 2016 and January 2019. We assessed disease control rate (DCR), progression-free survival (PFS), and overall survival (OS). Results There were 14 patients; the median age at the time of diagnosis and the median age at the initiation of Nal-IRI were 59.3 and 60.0 years, respectively. Nal-IRI in combination with 5-fluorouracil and folinic acid was administered as second-, third-, fourth-, and fifth-line treatment in 6 (43%), 5 (36%), 2 (14%), and 1 (7%) patient with metastatic disease, respectively. The objective DCR with Nal-IRI was 50% (7/14 patients). Six patients (43%) had partial response, and one patient (7%) had stable disease. Progressive disease was observed in seven patients. The median PFS and median OS following Nal-IRI initiation were 10.6 and 24.1 months, respectively. Conclusions This retrospective analysis provides the first evidence that Nal-IRI might exhibit a clinical meaningful antitumor activity in metastatic biliary tract cancer.

摘要

背景: 晚期、转移性胆道癌的治疗选择有限。关键的 NAPOLI-1 试验证明了纳米脂质体伊立替康 (Nal-IRI) 在吉西他滨预处理的转移性胰腺导管腺癌患者中的优越临床益处; 然而,nal-IRI 在胆道癌中的抗肿瘤活性尚不清楚。本文首次报道了 Nal-IRI 在胆道癌中的疗效。方法在这个多中心回顾性队列分析中,我们确定了 2016 年 5 月至 2019 年 1 月在其中一个研究中心在标准治疗下肿瘤进展后接受 Nal-IRI 联合 5-氟尿嘧啶和亚叶酸治疗的转移性胆道腺癌患者。。我们评估了疾病控制率 (DCR) 、无进展生存期 (PFS) 和总生存期 (OS)。结果 14 例患者,确诊时的中位年龄为 59.3 岁,初治时的中位年龄为 60.0 岁。Nal-IRI 联合 5-氟尿嘧啶和亚叶酸作为二线、三线、四线和五线治疗,分别给予 6 (43%) 、 5 (36%) 、转移性疾病患者分别为 2 例 (14%) 和 1 例 (7%)。伴 Nal-IRI 的客观 DCR 为 50% (7/14 例患者)。6 例患者 (43%) 部分缓解,1 例患者 (7%) 病情稳定。7 例患者病情进展。Nal-IRI 启动后的中位 PFS 和中位 OS 分别为 10.6 和 24.1 个月。结论本回顾性分析首次证明了 Nal-IRI 可能在转移性胆道癌中表现出临床有意义的抗肿瘤活性。

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影响因子:3.72
发表时间:2020-01-16
DOI:10.1093/ibd/izz325
作者列表:["Peverelle M","Paleri S","Hughes J","De Cruz P","Gow PJ"]

METHODS:BACKGROUND:The impact of inflammatory bowel disease (IBD) activity on long-term outcomes after liver transplantation (LT) for primary sclerosing cholangitis (PSC) is unknown. We examined the impact of post-LT IBD activity on clinically significant outcomes. METHODS:One hundred twelve patients undergoing LT for PSC from 2 centers were studied for a median of 7 years. Patients were divided into 3 groups according to their IBD activity after LT: no IBD, mild IBD, and moderate to severe IBD. Patients were classified as having moderate to severe IBD if they met at least 1 of 3 criteria: (i) Mayo 2 or 3 colitis or Simple Endoscopic Score-Crohn's Disease ≥7 on endoscopy; (ii) acute flare of IBD necessitating steroid rescue therapy; or (iii) post-LT colectomy for medically refractory IBD. RESULTS:Moderate to severe IBD at any time post-transplant was associated with a higher risk of Clostridium difficile infection (27% vs 8% mild IBD vs 8% no IBD; P = 0.02), colorectal cancer/high-grade dysplasia (21% vs 3% both groups; P = 0.004), post-LT colectomy (33% vs 3% vs 0%) and rPSC (64% vs 18% vs 20%; P < 0.001). Multivariate analysis revealed that moderate to severe IBD increased the risk of both rPSC (relative risk [RR], 8.80; 95% confidence interval [CI], 2.81-27.59; P < 0.001) and colorectal cancer/high-grade dysplasia (RR, 10.45; 95% CI, 3.55-22.74; P < 0.001). CONCLUSIONS:Moderate to severe IBD at any time post-LT is associated with a higher risk of rPSC and colorectal neoplasia compared with mild IBD and no IBD. Patients with no IBD and mild IBD have similar post-LT outcomes. Future prospective studies are needed to determine if more intensive treatment of moderate to severe IBD improves long-term outcomes in patients undergoing LT for PSC.

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影响因子:6.87
发表时间:2020-01-23
DOI:10.1002/hep.31140
作者列表:["Kunzmann LK","Schoknecht T","Poch T","Henze L","Stein S","Kriz M","Grewe I","Preti M","Hartl J","Pannicke N","Peiseler M","Sebode M","Zenouzi R","Horvatits T","Böttcher M","Petersen BS","Weiler-Normann C","Hess LU","Elise Ahrenstorf A","Lunemann S","Martrus G","Fischer L","Li J","Carambia A","Kluwe J","Huber S","Lohse AW","Franke A","Herkel J","Schramm C","Schwinge D"]

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