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纳米脂质体伊立替康(nal-IRI)用于胰腺癌的二线及三线治疗:单中心经验及文献综述

Second-line and third-line therapy with nanoliposomal irinotecan (nal-IRI) in pancreatic cancer: a single-center experience and review of literature.

作者信息

Möhring Christian, Frontado Graffe Freddy José, Bartels Alexandra, Sadeghlar Farsaneh, Zhou Taotao, Mahn Robert, Marinova Milka, Feldmann Georg, Brossart Peter, Glowka Tim R, Kalff Jörg C, Strassburg Christian P, Gonzalez-Carmona Maria A

机构信息

Department of Internal Medicine I, University Hospital Bonn, Bonn, Germany.

Department of Nuclear Medicine, University Hospital Bonn, Bonn, Germany.

出版信息

J Gastrointest Oncol. 2023 Feb 28;14(1):352-365. doi: 10.21037/jgo-22-632. Epub 2023 Feb 15.

Abstract

BACKGROUND

Prognosis of patients with pancreatic cancer is still extremely poor. First-line palliative therapies with FOLFIRINOX or gemcitabine/nab-paclitaxel have been established in the last decade. In the second-line, 5-FU/LV in combination with nanoliposomal irinotecan (nal-IRI) after gemcitabine has been shown to be effective. However, the use of nal-IRI as third-line therapy after FOLFIRINOX and gemcitabine-based chemotherapies is still controversial. In this study, we report about the use of 5-FU/LV + nal-IRI in a daily practice and analyze whether nal-IRI is an option as third-line therapy after FOLFIRINOX and gemcitabine/nab-paclitaxel.

METHODS

This is a single center retrospective analysis of patients with irresectable pancreatic cancer who were treated with 5-FU/LV and nal-IRI from 2017 to 2021 as second- or third-line palliative treatment. Overall survival (OS), progression-free survival (PFS) and toxicity were analyzed, and multivariate analysis was used to identify independent prognostic factors.

RESULTS

Twenty-nine patients receiving 5-FU/LV and nal-IRI were included in the analysis. The majority of patients (n=19) received 5-FU/nal-IRI as third-line therapy after pre-exposition to FOLFIRINOX and gemcitabine/nab-paclitaxel. Median OS and PFS were 9.33 months (95% CI: 3.37, 15.30) and 2.90 months (95% CI: 1.64, 4.16), respectively. Furthermore, patients receiving nal-IRI + 5-FU/LV as third-line treatment also showed some benefits, with no OS difference compared to second-line patients (9.33 10.27 months; HR: 1.85; 95% CI: 0.64, 5.41; P=0.253). Adverse effects were similar to reported trials.

CONCLUSIONS

In our study, the use of 5-FU/nal-IRI in unselected patients with advanced pancreatic cancer showed similar OS, PFS and tolerance as randomized prospective phase II/III trials. Interestingly, the use of 5-FU/nal-IRI seemed to be beneficial in third-line therapy, despite a pre-exposure to non-liposomal irinotecan.

摘要

背景

胰腺癌患者的预后仍然极差。在过去十年中,已确立了以FOLFIRINOX或吉西他滨/纳米白蛋白结合型紫杉醇进行一线姑息治疗。在二线治疗中,吉西他滨后使用5-氟尿嘧啶/亚叶酸钙联合纳米脂质体伊立替康(nal-IRI)已被证明是有效的。然而,nal-IRI作为FOLFIRINOX和基于吉西他滨的化疗后的三线治疗的应用仍存在争议。在本研究中,我们报告了5-氟尿嘧啶/亚叶酸钙+nal-IRI在日常临床中的应用,并分析nal-IRI是否可作为FOLFIRINOX和吉西他滨/纳米白蛋白结合型紫杉醇后的三线治疗选择。

方法

这是一项单中心回顾性分析,纳入了2017年至2021年接受5-氟尿嘧啶/亚叶酸钙和nal-IRI作为二线或三线姑息治疗的不可切除胰腺癌患者。分析了总生存期(OS)、无进展生存期(PFS)和毒性,并采用多变量分析来确定独立的预后因素。

结果

29例接受5-氟尿嘧啶/亚叶酸钙和nal-IRI治疗的患者纳入分析。大多数患者(n = 19)在接受FOLFIRINOX和吉西他滨/纳米白蛋白结合型紫杉醇预处理后,将5-氟尿嘧啶/nal-IRI作为三线治疗。中位OS和PFS分别为9.33个月(95%CI:3.37,15.30)和2.90个月(95%CI:1.64,4.16)。此外,接受nal-IRI + 5-氟尿嘧啶/亚叶酸钙作为三线治疗的患者也显示出一些益处,与二线治疗患者相比OS无差异(9.33对10.27个月;HR:1.85;95%CI:0.64,5.41;P = 0.253)。不良反应与报道的试验相似。

结论

在我们的研究中,在未选择的晚期胰腺癌患者中使用5-氟尿嘧啶/nal-IRI显示出与随机前瞻性II/III期试验相似的OS、PFS和耐受性。有趣的是,尽管之前使用过非脂质体伊立替康,但5-氟尿嘧啶/nal-IRI在三线治疗中似乎有益。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/714e/10007927/b123ecfb5253/jgo-14-01-352-f1.jpg

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