Retrospective Study
Copyright ©The Author(s) 2018. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Oncol. Nov 15, 2018; 10(11): 421-430
Published online Nov 15, 2018. doi: 10.4251/wjgo.v10.i11.421
Comparison of efficacy and safety between standard-dose and modified-dose FOLFIRINOX as a first-line treatment of pancreatic cancer
Huapyong Kang, Jung Hyun Jo, Hee Seung Lee, Moon Jae Chung, Seungmin Bang, Seung Woo Park, Si Young Song, Jeong Youp Park
Huapyong Kang, Jung Hyun Jo, Hee Seung Lee, Moon Jae Chung, Seungmin Bang, Seung Woo Park, Si Young Song, Jeong Youp Park, Division of Gastroenterology, Department of Internal Medicine, Yonsei University College of Medicine, Seodaemun-gu, Seoul 03722, South Korea
Author contributions: Kang H and Park JY led the study design; the study was supervised by Park JY. Kang H, Jo JH, Lee HS, Chung MJ, Bang S, Park SW, Song SY, and Park JY were contributed to the collection and assembly of data; Kang H did the data analysis; all authors interpreted the analyzed data; Kang H and Park JY wrote the manuscript; all authors reviewed every version of the manuscript and approved the final manuscript.
Institutional review board statement: This study was approved by the Institutional Review Board of Yonsei University Health System (Approval number: 4-2017-0757) and carried out in accordance with the Declaration of Helsinki.
Informed consent statement: The institutional review board waived the need for consent for this study due to its retrospective design.
Conflict-of-interest statement: All authors declare no conflicts-of-interest related to this article.
Data sharing statement: No additional data are available.
Open-Access: This 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:
Correspondence to: Jeong Youp Park, MD, PhD, Associate Professor, Division of Gastroenterology, Department of Internal Medicine, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul 03722, South Korea.
Telephone: +82-2-22281982 Fax: +82-2-3936884
Received: August 6, 2018
Peer-review started: August 7, 2018
First decision: August 31, 2018
Revised: September 7, 2018
Accepted: October 10, 2018
Article in press: October 10, 2018
Published online: November 15, 2018
Research background

Although FOLFIRINOX is one of the universally-used chemotherapies for pancreatic cancer, its relatively high rate of adverse events is still a major concern. Several studies suggest that dose-modified FOLFIRINOX (mFOLFIRINOX) can improve safety with comparable efficacy compared to the standard FOLFIRINOX (sFOLFIRINOX). However, clinical feasibility and the optimal strategy of mFOLFIRINOX remains unclear.

Research motivation

Previous studies on mFOLFIRINOX made conclusions based on comparing their results to the results of historical phase III trials of FOLFIRINOX. To date, direct comparative studies between sFOLFIRINOX and mFOLFIRINOX for pancreatic cancer is lacking.

Research objectives

We directly compared the safety and efficacy of sFOLFIRINOX and mFOLFIRINOX in a single study. This could help clarify the clinical applicability of mFOLFIRINOX.

Research methods

The medical records of 130 pancreatic cancer patients [sFOLFIRINOX (n = 88), mFOLFIRINOX (n = 42)] were retrospectively reviewed. The objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS) were compared for efficacy analysis. Severe (≥ grade three) adverse event (AE) rates of the two groups were compared for toxicity analysis.

Research results

Although the median relative dose intensities of each of the drugs were significantly lower in the mFOLFIRINOX group, the response rates and survival were not different between the two groups (ORR: 39.8% vs 35.7%, P = 0.656; DCR: 80.7% vs 83.3%, P = 0.716; PFS: 8.7 mo vs 8.1 mo, P = 0.272; OS: 13.9 mo vs 13.7 mo, P = 0.476). Severe AE rates, including neutropenia (83.0% vs 66.7%; P = 0.044), anorexia (48.9% vs 28.6%; P = 0.029), and diarrhea (13.6% vs 0.0%; P = 0.009), were significantly lower in the mFOLFIRINOX group.

Research conclusions

In this direct comparative restrospective study, mFOLFIRINOX showed comparable efficacy to sFOLFIRINOX, with a better toxicity profile. Given the relatively high toxicity of sFOLFIRINOX, initiating FOLFIRINOX treatment, if clinically required, with 75% of the standard-dose could be an appropriate option to reduce toxicity concerns without compromising efficacy.

Research perspectives

In the future, prospective comparative studies need to be conducted to determine the optimal dose modification of FOLFIRINOX and who will benefit from this strategy.