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ORIGINAL RESEARCH article

Front. Oncol.

Sec. Gastrointestinal Cancers: Hepato Pancreatic Biliary Cancers

Volume 15 - 2025 | doi: 10.3389/fonc.2025.1626689

This article is part of the Research TopicDiagnosis and Management of Pancreatic CancerView all articles

Efficacy of third-line chemotherapy following nanoliposomal irinotecan combined with fluorouracil and folinic acid as second-line treatment for unresectable pancreatic cancer

Provisionally accepted
Keisuke  MiwaKeisuke Miwa1Reina  KawasakiReina Kawasaki2Mototsugu  ShimokawaMototsugu Shimokawa3,4Taiga  OtsukaTaiga Otsuka5Tanaka  ToshimitsuTanaka Toshimitsu6Masaru  FukahoriMasaru Fukahori6Taro  ShibukiTaro Shibuki7,8Junichi  NakazawaJunichi Nakazawa9Shiho  ArimaShiho Arima10Futa  KogaFuta Koga11Yujiro  UedaYujiro Ueda12Yoshihito  KubotsuYoshihito Kubotsu13Hozumi  ShimokawaHozumi Shimokawa14,15Shigeyuki  TakeshitaShigeyuki Takeshita16Kazuo  NishikawaKazuo Nishikawa17Azusa  KomoriAzusa Komori17,18Satoshi  OtsuSatoshi Otsu17Ayumu  HosokawaAyumu Hosokawa19Tatsunori  SakaiTatsunori Sakai20Hisanobu  OdaHisanobu Oda21Machiko  KawahiraMachiko Kawahira22Shuji  AritaShuji Arita23Takuya  HondaTakuya Honda24Hiroki  TaguchiHiroki Taguchi25,26Kengo  TsuneyoshiKengo Tsuneyoshi25Toshihiro  FujitaToshihiro Fujita27Takahiro  SakaeTakahiro Sakae27Yasunori  KawaguchiYasunori Kawaguchi28Tsuyoshi  ShirakawaTsuyoshi Shirakawa29,30*Toshihiko  MizutaToshihiko Mizuta31Kenji  MitsugiKenji Mitsugi32
  • 1Multidisciplinary Treatment Cancer Center, Kurume University Hospital, Kuurme, Fukuoka, Japan
  • 2Division of Integrative Medical Oncology, Saiseikai Kumamoto Hospital, Kumamoto, Japan
  • 3Department of Biostatistics, Yamaguchi University Graduate School of Medicine, Ube-shi, Yamaguchi, Japan
  • 4Clinical Research Institute, National Kyushu Cancer Center, Fukuoka-shi, Fukuoka, Fukuoka-shi, Fukuoka, Japan
  • 5Department of Internal Medicine, Minato Medical Clinic, Fukuoka-shi, Fukuoka, Japan, Fukuoka-shi, Fukuoka, Japan
  • 6Multidisciplinary Treatment Cancer Center, Kurume University Hospital, Kurume, Fukuoka, Japan
  • 7Department for the Promotion of Drug and Diagnostic Development, Division of Drug and Diagnostic Development Promotion, Translational Research Support Office, National Cancer Center Hospital East, Kashiwa-shi, Chiba, Japan
  • 8Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital East, Kashiwa-shi, Chiba, Japan
  • 9Department of Medical Oncology, Kagoshima City Hospital, Kagoshima-shi, Kagoshima, Japan
  • 10Digestive and Lifestyle Diseases, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima-shi, Kagoshima, Japan
  • 11Department of Hepatobiliary and Pancreatology, Saga Medical Center Koseikan, Saga-shi, Saga, Japan
  • 12Department of Hematology and Oncology, Japanese Red Cross Kumamoto Hospital, Kumamoto-shi, Kumamoto, Japan
  • 13Department of Internal Medicine, Karatsu Red Cross Hospital, Karatsu-shi, Saga, Japan
  • 14Department of Hematology Oncology, Japan Community Healthcare Organization Kyushu Hospital, Kitakyushu-shi, Fukuoka, Japan
  • 15Department of Medical Oncology, Hamanomachi Hospital, Fukuoka-shi, Fukuoka, Japan
  • 16Department of Gastroenterology, Japanese Red Cross Nagasaki Genbaku Hospital, Nagasaki-shi, Nagasaki, Japan
  • 17Department of Medical Oncology and Hematology, Oita University Faculty of Medicine, Yufu-shi, Oita, Japan
  • 18Department of Gastrointestinal Medical Oncology, National Hospital Organization Shikoku Cancer Center, Matsuyama-shi, Ehime, Japan
  • 19Department of Clinical Oncology, University of Miyazaki Hospital, Miyazaki-shi, Miyazaki, Japan
  • 20Department of Medical Oncology, NHO Kumamoto Medical Center, Kumamoto-shi, Kumamoto, Japan
  • 21Division of Integrative Medical Oncology, Saiseikai Kumamoto Hospital, Kumamoto-shi, Kumamoto, Japan
  • 22Department of Gastroenterology, Kagoshima Kouseiren Hospital, Kagoshima-shi, Kagoshima, Japan
  • 23Department of Chemotherapy, Miyazaki Prefectural Miyazaki Hospital, Miyazaki-shi, Miyazaki, Japan
  • 24Department of Gastroenterology and Hepatology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki-shi, Nagasaki, Japan
  • 25Department of Gastroenterology, Izumi General Medical Center, Izumi-shi, Kagoshima, Japan
  • 26Department of Gastroenterology, Kagoshima City Hospital, Kagoshima-shi, Kagoshima, Japan
  • 27Department of Gastroenterology, Saiseikai Sendai Hospital, Satsumasendai-shi, Kagoshima, Japan
  • 28Department of Gastroenterology, Asakura Medical Association Hospital, Asakura-shi, Fukuoka, Japan
  • 29Clinical Hematology Oncology Treatment Study Group, Fukuoka-shi, Fukuoka, Japan
  • 30Department of Medical Checkup Center, Eikoh Hospital, Kasuya-gun, Fukuoka, Japan
  • 31Department of Internal Medicine, Fujikawa Hospital, Saga-shi, Saga, Japan
  • 32Department of Medical Oncology, Sasebo Kyosai Hospital, Sasebo-shi, Nagasaki, Japan

The final, formatted version of the article will be published soon.

The significance of third-line chemotherapy (CTx) in unresectable pancreatic cancer (UPC) remains unclear. This study evaluated the therapeutic impact of third-line CTx after nanoliposomal irinotecan and fluorouracil combined with folinic acid (nal-IRI + 5-FU/LV) therapy as second-line CTx for UPC.Methods: Between June 2020 and May 2021, 104 patients who received nal-IRI + 5-FU/LV therapy as second-line CTx were retrospectively analyzed for post-discontinuation survival (PDS) and overall survival (OS). Comparisons were made between patients transitioning to third-line CTx and those receiving best supportive care (BSC), using a Cox proportional hazards model adjusted for patient background.Results: Of the cohort, 34 patients received third-line CTx, whereas 61 transitioned to BSC. The median OS from first-line CTx in the third-line CTx group was 18.0 months, with a median OS of 9.7 months from second-line CTx. Adjusted median PDS following second-line CTx was 6.5 months for the third-line CTx group compared to 2.3 months for the BSC group (adjusted hazard ratio 0.16; 95% confidence interval 0.08-0.32; P < 0.01).Third-line CTx should be actively considered for patients with UPC, as the approach may significantly extend survival in those who can tolerate the treatment.

Keywords: Pancreatic Cancer, chemotherapy, third-line treatment, Nanoliposomal irinotecan, Best supportive care

Received: 11 May 2025; Accepted: 03 Jul 2025.

Copyright: © 2025 Miwa, Kawasaki, Shimokawa, Otsuka, Toshimitsu, Fukahori, Shibuki, Nakazawa, Arima, Koga, Ueda, Kubotsu, Shimokawa, Takeshita, Nishikawa, Komori, Otsu, Hosokawa, Sakai, Oda, Kawahira, Arita, Honda, Taguchi, Tsuneyoshi, Fujita, Sakae, Kawaguchi, Shirakawa, Mizuta and Mitsugi. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Tsuyoshi Shirakawa, Clinical Hematology Oncology Treatment Study Group, Fukuoka-shi, Fukuoka, Japan

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