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©The Author(s) 2018. Published by Baishideng Publishing Group Inc. All rights reserved.
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 ClinicalTrials.gov, 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.
CONSORT 2010 statement: The guidelines of the CONSORT 2010 Statement have been adopted in 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: http://creativecommons.org/licenses/by-nc/4.0/
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.
bang7028@yuhs.ac
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
Processing time: 86 Days and 10.7 Hours
AIM
To evaluate the efficacy and safety of modified FOLFIRINOX as a second-line treatment for gemcitabine (GEM)-refractory unresectable pancreatic cancer (PC).
METHODS
This study was a prospective, multicenter, one-arm, open-label, phase II trial. Patients with unresectable PC, who showed disease progression during GEM-based chemotherapy 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 phase I study of FOLFIRINOX. The objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), adverse events were evaluated. Additionally, changes in quality of life (QoL) were assessed using a questionnaire on QoL.
RESULTS
Between August 2015 and May 2016, a total of 48 patients were enrolled. The median follow-up time was 259 d with a median of 8.5 cycles. 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, followed by febrile neutropenia (16.7%). 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).
CONCLUSION
FOLFIRINOX with RIO showed acceptable toxicity and promising efficacy for GEM-refractory unresectable PC. However, this treatment requires careful observation of treatment-related hematologic toxicities.
Core tip: For gemcitabine (GEM)-refractory unresectable pancreatic cancer (PC), there are limited options of second-line chemotherapy regimen. To find new treatment option for GEM-refractory unresectable PC, we conducted a multicenter phase II trial, which evaluated the efficacy and safety of uniquely modified FOLFIRINOX with reduced irinotecan and oxaliplatin. In our results, FOLFIRINOX with reduced irinotecan and oxaliplatin showed acceptable toxicity and promising efficacy. With careful observation of treatment-related hematologic toxicities, this chemotherapy regimen is a promising option for patients with GEM-refractory PC after first-line treatment failure.
