Nanoliposomal irinotecan with fluorouracil and folinic acid in patients with unresectable or recurrent pancreatic cancer: a multicenter observational study (NAPOLEON-2)

Background: Nanoliposomal irinotecan with fluorouracil and folinic acid (NFF) is a standard second- or later-line regimen after gemcitabine-based therapy for patients with unresectable or recurrent pancreatic cancer (urPC). However, limited prospective clinical data on the efficacy and safety of NFF...

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Main Authors: T. Shirakawa, M. Shimokawa, T. Otsuka, Y. Shinohara, K. Toyodome, W. Kusano, J. Nakazawa, T. Kodama, M. Kawahira, H. Shimokawa, T. Koike, F. Koga, S. Yunotani, S. Nakashita, N. Oza, S. Noge, K. Murayama, H. Oda, N. Mitsui, R. Kawasaki, T. Morikita, S. Takeshita, S. Arima, R. Shibata, A. Kakihara, T. Yoshihiro, T. Imajima, S. Yamaga, S. Arita, Y. Kawaguchi, K. Nishikawa, T. Inagaki, S. Otsu, H. Taguchi, K. Jikuya, T. Terada, T. Sakai, Y. Ueda, T. Sakae, H. Sawase, K. Nio, N. Araki, K. Sakai, Y. Ide, T. Shibuki, K. Miwa, Y. Kubotsu, A. Hosokawa, A. Komori, T. Honda, K. Tsuneyoshi, T. Fujita, T. Mizuta, K. Mitsugi
Format: Article
Language:English
Published: Elsevier 2025-06-01
Series:ESMO Gastrointestinal Oncology
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Online Access:http://www.sciencedirect.com/science/article/pii/S2949819825000196
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author T. Shirakawa
M. Shimokawa
T. Otsuka
Y. Shinohara
K. Toyodome
W. Kusano
J. Nakazawa
T. Kodama
M. Kawahira
H. Shimokawa
T. Koike
F. Koga
S. Yunotani
S. Nakashita
N. Oza
S. Noge
K. Murayama
H. Oda
N. Mitsui
R. Kawasaki
T. Morikita
S. Takeshita
S. Arima
R. Shibata
A. Kakihara
T. Yoshihiro
T. Imajima
S. Yamaga
S. Arita
Y. Kawaguchi
K. Nishikawa
T. Inagaki
S. Otsu
H. Taguchi
K. Jikuya
T. Terada
T. Sakai
Y. Ueda
T. Sakae
H. Sawase
M. Kawahira
K. Nio
N. Araki
K. Sakai
Y. Ide
T. Shibuki
K. Miwa
Y. Kubotsu
A. Hosokawa
A. Komori
T. Honda
K. Tsuneyoshi
T. Fujita
T. Mizuta
K. Mitsugi
author_facet T. Shirakawa
M. Shimokawa
T. Otsuka
Y. Shinohara
K. Toyodome
W. Kusano
J. Nakazawa
T. Kodama
M. Kawahira
H. Shimokawa
T. Koike
F. Koga
S. Yunotani
S. Nakashita
N. Oza
S. Noge
K. Murayama
H. Oda
N. Mitsui
R. Kawasaki
T. Morikita
S. Takeshita
S. Arima
R. Shibata
A. Kakihara
T. Yoshihiro
T. Imajima
S. Yamaga
S. Arita
Y. Kawaguchi
K. Nishikawa
T. Inagaki
S. Otsu
H. Taguchi
K. Jikuya
T. Terada
T. Sakai
Y. Ueda
T. Sakae
H. Sawase
M. Kawahira
K. Nio
N. Araki
K. Sakai
Y. Ide
T. Shibuki
K. Miwa
Y. Kubotsu
A. Hosokawa
A. Komori
T. Honda
K. Tsuneyoshi
T. Fujita
T. Mizuta
K. Mitsugi
author_sort T. Shirakawa
collection DOAJ
description Background: Nanoliposomal irinotecan with fluorouracil and folinic acid (NFF) is a standard second- or later-line regimen after gemcitabine-based therapy for patients with unresectable or recurrent pancreatic cancer (urPC). However, limited prospective clinical data on the efficacy and safety of NFF in a real-world setting have been presented. Therefore, we conducted this observational, real-world study to investigate the efficacy and safety of NFF. Patients and methods: We collected prospective data of urPC patients treated with NFF in 17 hospitals in Japan from 2021 to 2023. The primary endpoint was overall survival (OS). Secondary endpoints were overall response rate, disease control rate, progression-free survival, dose intensity, and adverse events (AEs). Results: NFF was administered to 150 patients with a mean age of 72 years. The median follow-up period was 7.2 months. All patients had previously received gemcitabine-based therapy. The median OS was 7.8 months; median progression-free survival was 3.7 months; median overall response rate was 11%; and median disease control rate was 56%. Median relative dose intensity was 72.7% with nanoliposomal irinotecan and 79.4% with fluorouracil. Grade 3/4 hematological and nonhematological AEs occurred in 52 and 70 patients, respectively. Neutropenia (28%) and anorexia (19%) were common grade 3/4 AEs. Subanalysis of patients with second-line and third- or later-line therapy demonstrated no significant difference in OS (7.4 versus 7.8 months, respectively; P = 0.88). Integrated analysis of the prospective and retrospective phases of the study showed that median OS was 8.0 months. Conclusions: NFF has an appropriate efficacy and safety profile and is a candidate for second- or later-line therapy for urPC.
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spelling doaj-art-5dcb7e58eebf406a8ee23c82da8a9f272025-08-20T03:21:32ZengElsevierESMO Gastrointestinal Oncology2949-81982025-06-01810015010.1016/j.esmogo.2025.100150Nanoliposomal irinotecan with fluorouracil and folinic acid in patients with unresectable or recurrent pancreatic cancer: a multicenter observational study (NAPOLEON-2)T. Shirakawa0M. Shimokawa1T. Otsuka2Y. Shinohara3K. Toyodome4W. Kusano5J. Nakazawa6T. Kodama7M. Kawahira8H. Shimokawa9T. Koike10F. Koga11S. Yunotani12S. Nakashita13N. Oza14S. Noge15K. Murayama16H. Oda17N. Mitsui18R. Kawasaki19T. Morikita20S. Takeshita21S. Arima22R. Shibata23A. Kakihara24T. Yoshihiro25T. Imajima26S. Yamaga27S. Arita28Y. Kawaguchi29K. Nishikawa30T. Inagaki31S. Otsu32H. Taguchi33K. Jikuya34T. Terada35T. Sakai36Y. Ueda37T. Sakae38H. Sawase39M. Kawahira40K. Nio41N. Araki42K. Sakai43Y. Ide44T. Shibuki45K. Miwa46Y. Kubotsu47A. Hosokawa48A. Komori49T. Honda50K. Tsuneyoshi51T. Fujita52T. Mizuta53K. Mitsugi54Clinical Hematology Oncology Treatment Study Group, Fukuoka, Japan; Eikoh Hospital, Fukuoka, Japan; Correspondence to: Dr Tsuyoshi Shirakawa, Researcher of Clinical Hematology Oncology Treatment Study Group, 1-14-6 Muromi-gaoka, Nishi-ku, Fukuoka-shi, Fukuoka 819-0030, Japan. Tel: +81-92-406-4166; Fax: +81-92-406-8356 Director of Medical Checkup Center, Eikoh Hospital, 3-8-15 Befu-nishi, Shime-machi, Kasuya-gun, Fukuoka 811-2232, Japan. Tel: +81-92-935-0147; Fax: +81-92-936-3370Clinical Research Institute, National Kyushu Cancer Center, Fukuoka, Japan; Department of Biostatistics, Yamaguchi University Graduate School of Medicine, Yamaguchi, JapanDepartment of Internal Medicine, Minato Medical Clinic, Fukuoka, JapanDepartment of Hematology and Oncology, Japan Community Healthcare Organization Kyushu Hospital, Fukuoka, JapanDigestive and Lifestyle Diseases, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, JapanDepartment of Chemotherapy, Miyazaki Prefectural Miyazaki Hospital, Miyazaki, JapanDepartment of Medical Oncology, Kagoshima City Hospital, Kagoshima, JapanDepartment of Medical Oncology, Kagoshima City Hospital, Kagoshima, JapanDepartment of Medical Oncology, Kagoshima City Hospital, Kagoshima, JapanDepartment of Hematology and Oncology, Japan Community Healthcare Organization Kyushu Hospital, Fukuoka, JapanDepartment of Hematology and Oncology, Japan Community Healthcare Organization Kyushu Hospital, Fukuoka, JapanDepartment of Hepatobiliary and Pancreatology, Saga Medical Center Koseikan, Saga, JapanDepartment of Hepatobiliary and Pancreatology, Saga Medical Center Koseikan, Saga, JapanDepartment of Hepatobiliary and Pancreatology, Saga Medical Center Koseikan, Saga, JapanDepartment of Hepatobiliary and Pancreatology, Saga Medical Center Koseikan, Saga, JapanDepartment of Hepatobiliary and Pancreatology, Saga Medical Center Koseikan, Saga, JapanDepartment of Hepatobiliary and Pancreatology, Saga Medical Center Koseikan, Saga, JapanDivision of Integrative Medical Oncology, Saiseikai Kumamoto Hospital, Kumamoto, JapanDivision of Integrative Medical Oncology, Saiseikai Kumamoto Hospital, Kumamoto, JapanDivision of Integrative Medical Oncology, Saiseikai Kumamoto Hospital, Kumamoto, JapanDivision of Integrative Medical Oncology, Saiseikai Kumamoto Hospital, Kumamoto, JapanDepartment of Gastroenterology, Japanese Red Cross Nagasaki Genbaku Hospital, Nagasaki, JapanDigestive and Lifestyle Diseases, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, JapanDigestive and Lifestyle Diseases, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, JapanDigestive and Lifestyle Diseases, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, JapanDepartment of Medical Oncology, Sasebo Kyosai Hospital, Nagasaki, JapanDepartment of Medical Oncology, Sasebo Kyosai Hospital, Nagasaki, JapanDepartment of Medical Oncology, Sasebo Kyosai Hospital, Nagasaki, JapanDepartment of Chemotherapy, Miyazaki Prefectural Miyazaki Hospital, Miyazaki, JapanDepartment of Gastroenterology, Asakura Medical Association Hospital, Fukuoka, JapanDepartment of Medical Oncology and Hematology, Oita University Faculty of Medicine, Oita, JapanDepartment of Medical Oncology and Hematology, Oita University Faculty of Medicine, Oita, JapanDepartment of Medical Oncology and Hematology, Oita University Faculty of Medicine, Oita, JapanDepartment of Gastroenterology, Imamura General Hospital, Kagoshima, JapanDepartment of Gastroenterology, Imamura General Hospital, Kagoshima, JapanDepartment of Gastroenterology, Imamura General Hospital, Kagoshima, JapanDepartment of Medical Oncology, NHO Kumamoto Medical Center, Kumamoto, JapanDepartment of Hematology and Oncology, Japanese Red Cross Kumamoto Hospital, Kumamoto, JapanDepartment of Gastroenterology, Saiseikai Sendai Hospital, Kagoshima, JapanDepartment of Internal Medicine, National Hospital Organization Saga Hospital, Saga, JapanDepartment of Gastroenterology, Kagoshima Kouseiren Hospital, Kagoshima, JapanDepartment of Medical Oncology, Hamanomachi Hospital, Fukuoka, JapanDepartment of Gastroenterology, Saiseikai Sendai Hospital, Kagoshima, JapanDepartment of Medical Oncology, NHO Kumamoto Medical Center, Kumamoto, JapanDepartment of Internal Medicine, National Hospital Organization Saga Hospital, Saga, JapanDepartment for the Promotion of Drug and Diagnostic Development, Division of Drug and Diagnostic Development Promotion, Translational Research Support Office, National Cancer Center Hospital East, Chiba, Japan; Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital East, Chiba, JapanMultidisciplinary Treatment Cancer Center, Kurume University Hospital, Fukuoka, JapanDepartment of Internal Medicine, Karatsu Red Cross Hospital, Saga, JapanDepartment of Clinical Oncology, University of Miyazaki Hospital, Miyazaki, JapanDepartment of Medical Oncology and Hematology, Oita University Faculty of Medicine, Oita, JapanDepartment of Gastroenterology and Hepatology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, JapanDepartment of Gastroenterology, Izumi General Medical Center, Kagoshima, JapanDepartment of Gastroenterology, Saiseikai Sendai Hospital, Kagoshima, JapanDepartment of Internal Medicine, Fujikawa Hospital, Saga, JapanDepartment of Medical Oncology, Sasebo Kyosai Hospital, Nagasaki, Japan; Dr Kenji Mitsugi, Department of Medical Oncology, Sasebo Kyosai Hospital, 10-17 Shimanji-cho, Sasebo-shi, Nagasaki 857-8575, Japan. Tel: +81-956-22-5136; Fax: +81-956-25-0662Background: Nanoliposomal irinotecan with fluorouracil and folinic acid (NFF) is a standard second- or later-line regimen after gemcitabine-based therapy for patients with unresectable or recurrent pancreatic cancer (urPC). However, limited prospective clinical data on the efficacy and safety of NFF in a real-world setting have been presented. Therefore, we conducted this observational, real-world study to investigate the efficacy and safety of NFF. Patients and methods: We collected prospective data of urPC patients treated with NFF in 17 hospitals in Japan from 2021 to 2023. The primary endpoint was overall survival (OS). Secondary endpoints were overall response rate, disease control rate, progression-free survival, dose intensity, and adverse events (AEs). Results: NFF was administered to 150 patients with a mean age of 72 years. The median follow-up period was 7.2 months. All patients had previously received gemcitabine-based therapy. The median OS was 7.8 months; median progression-free survival was 3.7 months; median overall response rate was 11%; and median disease control rate was 56%. Median relative dose intensity was 72.7% with nanoliposomal irinotecan and 79.4% with fluorouracil. Grade 3/4 hematological and nonhematological AEs occurred in 52 and 70 patients, respectively. Neutropenia (28%) and anorexia (19%) were common grade 3/4 AEs. Subanalysis of patients with second-line and third- or later-line therapy demonstrated no significant difference in OS (7.4 versus 7.8 months, respectively; P = 0.88). Integrated analysis of the prospective and retrospective phases of the study showed that median OS was 8.0 months. Conclusions: NFF has an appropriate efficacy and safety profile and is a candidate for second- or later-line therapy for urPC.http://www.sciencedirect.com/science/article/pii/S2949819825000196nanoliposomal irinotecanpancreatic cancerchemotherapyprospectivereal-world data
spellingShingle T. Shirakawa
M. Shimokawa
T. Otsuka
Y. Shinohara
K. Toyodome
W. Kusano
J. Nakazawa
T. Kodama
M. Kawahira
H. Shimokawa
T. Koike
F. Koga
S. Yunotani
S. Nakashita
N. Oza
S. Noge
K. Murayama
H. Oda
N. Mitsui
R. Kawasaki
T. Morikita
S. Takeshita
S. Arima
R. Shibata
A. Kakihara
T. Yoshihiro
T. Imajima
S. Yamaga
S. Arita
Y. Kawaguchi
K. Nishikawa
T. Inagaki
S. Otsu
H. Taguchi
K. Jikuya
T. Terada
T. Sakai
Y. Ueda
T. Sakae
H. Sawase
M. Kawahira
K. Nio
N. Araki
K. Sakai
Y. Ide
T. Shibuki
K. Miwa
Y. Kubotsu
A. Hosokawa
A. Komori
T. Honda
K. Tsuneyoshi
T. Fujita
T. Mizuta
K. Mitsugi
Nanoliposomal irinotecan with fluorouracil and folinic acid in patients with unresectable or recurrent pancreatic cancer: a multicenter observational study (NAPOLEON-2)
ESMO Gastrointestinal Oncology
nanoliposomal irinotecan
pancreatic cancer
chemotherapy
prospective
real-world data
title Nanoliposomal irinotecan with fluorouracil and folinic acid in patients with unresectable or recurrent pancreatic cancer: a multicenter observational study (NAPOLEON-2)
title_full Nanoliposomal irinotecan with fluorouracil and folinic acid in patients with unresectable or recurrent pancreatic cancer: a multicenter observational study (NAPOLEON-2)
title_fullStr Nanoliposomal irinotecan with fluorouracil and folinic acid in patients with unresectable or recurrent pancreatic cancer: a multicenter observational study (NAPOLEON-2)
title_full_unstemmed Nanoliposomal irinotecan with fluorouracil and folinic acid in patients with unresectable or recurrent pancreatic cancer: a multicenter observational study (NAPOLEON-2)
title_short Nanoliposomal irinotecan with fluorouracil and folinic acid in patients with unresectable or recurrent pancreatic cancer: a multicenter observational study (NAPOLEON-2)
title_sort nanoliposomal irinotecan with fluorouracil and folinic acid in patients with unresectable or recurrent pancreatic cancer a multicenter observational study napoleon 2
topic nanoliposomal irinotecan
pancreatic cancer
chemotherapy
prospective
real-world data
url http://www.sciencedirect.com/science/article/pii/S2949819825000196
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