Clinical Trials Study
Copyright ©The Author(s) 2018. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Oncol. Dec 15, 2018; 10(12): 505-515
Published online Dec 15, 2018. doi: 10.4251/wjgo.v10.i12.505
Multicenter phase II trial of modified FOLFIRINOX in gemcitabine-refractory pancreatic cancer
Moon Jae Chung, Huapyong Kang, Ho Gak Kim, Jong Jin Hyun, Jun Kyu Lee, Kwang Hyuck Lee, Myung Hwan Noh, Dae Hwan Kang, Sang Hyub Lee, Seungmin Bang, Pancreatobiliary Cancer Study Group of Korean Society of Gastrointestinal Cancer
Moon Jae Chung, Huapyong Kang, Seungmin Bang, Division of Gastroenterology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul 03722, South Korea
Ho Gak Kim, Department of Internal Medicine, Daegu Catholic University School of Medicine, Daegu 42471, South Korea
Jong Jin Hyun, Department of Internal Medicine, Korea University Ansan Hospital, Korea University College of Medicine, Ansan 15355, South Korea
Jun Kyu Lee, Department of Internal Medicine, Dongguk University Ilsan Hospital, Dongguk University College of Medicine, Goyang 10326, South Korea
Kwang Hyuck Lee, Division of Gastroenterology, Department of Internal Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, South Korea
Myung Hwan Noh, Department of Internal Medicine, Dong-A University College of Medicine, Busan 49201, South Korea
Dae Hwan Kang, Department of Internal Medicine, Medical Research Institute, Pusan National University School of Medicine and Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Yangsan 50612, South Korea
Sang Hyub Lee, Departments of Internal Medicine and Liver Research Institute, Seoul National University Hospital, Seoul National University College of Medicine, Seoul 03080, South Korea
Author contributions: Chung MJ, Lee SH and Bang S led the study design; the study was managed by Lee SH and Bang S; Kang H and Chung MJ performed the data analysis; Chung MJ, Kang H, Kim HG, Hyun JJ, Lee JK, Lee KH, Noh MH, Kang DH, Lee SH and Bang S interpreted the data; Chung MJ, Kang H and Bang S wrote the manuscript; all versions of the manuscript were reviewed by Chung MJ, Kang H, Kim HG, Hyun JJ, Lee JK, Lee KH, Noh MH, Kang DH and Lee SH; all authors approved the final manuscript; Chung MJ and Kang H contributed equally to this work as primary authors; Lee SH and Bang S contributed equally to this work as corresponding authors.
Institutional review board statement: This study was approved by the Institutional Review Board of all participating institutions and carried out in accordance with the Declaration of Helsinki.
Clinical trial registration statement: This trial is registered with, number NCT02440958.
Informed consent statement: Written, informed consent was obtained from each participant after potential treatment complications had been fully explained.
Conflict-of-interest statement: All authors declare no conflicts-of-interest related to this article.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Corresponding author to: Seungmin Bang, MD, PhD, Professor, Division of Gastroenterology, Department of Internal Medicine, Yonsei University College of Medicine, 50-1, Yonsei-ro, Seodaemun-gu, Seoul 03722, South Korea.
Telephone: +82-2-22281932 Fax: +82-2-3936884
Received: September 19, 2018
Peer-review started: September 19, 2018
First decision: October 15, 2018
Revised: October 24, 2018
Accepted: November 25, 2018
Article in press: November 26, 2018
Published online: December 15, 2018
Research background

Proper second-line treatment can improve survival of patients with unresectable pancreatic cancer (PC) who fail first-line treatment with gemcitabine (GEM)-based regimen. Although some previous phase III trials showed survival improvement with their study regimens, the standard second-line treatment remains unclear.

Research motivation

FOLFIRINOX, a standard first-line treatment for PC, has been proposed as a second-line treatment regimen; however, concerns about relatively high toxicity limited broad use of FOLFIRINOX as a second-line therapy.

Research objectives

We evaluated the efficacy and safety of modified dose of FOLFIRINOX as a second-line treatment for GEM-refractory unresectable PC.

Research methods

In this prospective, multicenter, one-arm, open-label, phase II trial, unresectable PC patients, who showed disease progression during GEM-based therapy were enrolled. All patients were administered FOLFIRINOX with reduced irinotecan and oxaliplatin (RIO; irinotecan 120 mg/m2 and oxaliplatin 60 mg/m2), which was set according to the previous phase I study of FOLFIRINOX, with the standard dose of 5-fluorouracil (5-FU). The objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), adverse events, and changes in quality of life (QoL) were evaluated.

Research results

A total of 48 patients were enrolled in eight Korean centers. The ORR and DCR were 18.8% and 62.5%, respectively, including one patient who showed complete remission. The median PFS was 5.8 mo [95% confidence interval (CI): 3.7-7.9] and median OS was 9.0 mo (95%CI: 6.4-11.6). Neutropenia (64.6%) was the most common grade 3-4 adverse event. Although 14.6% of patients experienced grade 3 fatigue, most non-hematologic AEs were under grade 2. In the QoL analysis, the global health status score before treatment was not different from the score at the last visit after treatment (45.43 ± 22.88 vs 48.66 ± 24.14, P = 0.548).

Research conclusions

FOLFIRINOX with RIO showed acceptable tolerability for patients in terms of patient QoL and may be considered as a treatment option in patients with GEM-refractory unresectable PC. However, the presence of hematologic toxicities should be carefully observed and the routine use of granulocyte colony-stimulating factor should be considered to minimize the risk of hematologic toxicities.

Research perspectives

Prospective study with larger population comparing the efficacy and safety between FOLFIRINOX with RIO and 5-FU plus leucovorin needs to be conducted.