Real-world dose reduction of standard and modified FOLFIRINOX in metastatic pancreatic cancer: a systematic review, evidence-mapping, and meta-analysis

Kwangrok Jung; Suhyun Choi; Hyunjoo Song; Kyuhan Kwak; Soyeon Anh; Jae Hyup Jung; Bomi Kim; Jinwoo Ahn; Jaihwan Kim; Jin-Hyeok Hwang; Jong-Chan Lee

doi:10.1177/17588359231175441

Real-world dose reduction of standard and modified FOLFIRINOX in metastatic pancreatic cancer: a systematic review, evidence-mapping, and meta-analysis

Ther Adv Med Oncol. 2023 Jun 29:15:17588359231175441. doi: 10.1177/17588359231175441. eCollection 2023.

Authors

Kwangrok Jung¹, Suhyun Choi¹, Hyunjoo Song², Kyuhan Kwak², Soyeon Anh³, Jae Hyup Jung¹, Bomi Kim¹, Jinwoo Ahn¹, Jaihwan Kim^{1

4}, Jin-Hyeok Hwang^{1

4}, Jong-Chan Lee^{5

4}

Affiliations

¹ Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea.
² School of Computer Science and Engineering, Soongsil University, Seoul, Korea.
³ Division of Statistics, Medical Research Collaborating Center, Seoul National University Bundang Hospital, Seongnam, Korea.
⁴ College of Medicine, Seoul National University, Seoul, Korea.
⁵ Department of Internal Medicine, Seoul National University Bundang Hospital, 82, Gumi-ro 173 Beon-gil, Bundang-gu, Seongnam, Gyeonggi-do 13620, Korea.

Abstract

Background: FOLFIRINOX, used in metastatic pancreatic cancer (MPC), is highly efficacious but also toxic. Various dose modifications for FOLFIRINOX have been introduced to reduce toxicity. However, these studies lack a unified pattern for 'planned' dose modification, and the 'actually administered' dose varied more.

Objective: To map a 10-year trend for 'planned' and 'actual' doses of FOLFIRINOX and investigate the clinical outcomes according to dose modification.

Data sources and methods: A comprehensive systematic literature search was conducted from January 2011 to September 2021. All studies for FOLFIRINOX as first-line treatment in MPC were considered. Selected studies were firstly classified according to prospective versus retrospective research, secondly standard versus modified FOLFIRINOX, and thirdly 'planned' versus 'actual' dose. For evidence-mapping for the trend of dose modification, we developed a web-based interactive bubble-plot program (www.RDI-map.com). Objective response rate (ORR) and hematologic toxicity were set as endpoints for the comparison of clinical outcomes according to dose modification.

Results: A total of 37 studies were identified for evidence-mapping (11 prospective and 26 retrospective studies). There were 12 different types of 'planned' dose modification in FOLFIRINOX ranging 75-100% oxaliplatin, 75-100% irinotecan, 0-100% 5-fluorouracil (5-FU) bolus, and 75-133% 5-FU continuous injection. The 'actual' dose further decreased to 54-96%, 61-88%, 0-92%, and 63-98%, respectively. For the standard versus modified FOLFIRINOX, the ORR was 28.2% (95% CI: 22.5-33.9%) and 33.8% (95% CI: 30.3-37.3%), respectively (p = 0.100), and the incidence of febrile neutropenia was 11.6% (95% CI: 0-16.0%) and 5.5% (95% CI: 0-8.9%), respectively (p = 0.030).

Conclusions: RDI-map.com enables multifactorial evidence-mapping for practical FOLFIRINOX dose reduction. The pattern of dose modification was not consistent across studies, and there was a significant gap between the 'planned' and 'actual' doses. Modified FOLFIRINOX showed similar efficacy to the standard regimen with reduced incidence of febrile neutropenia.

Keywords: dose modification; evidence-mapping; metastatic pancreatic cancer; modified FOLFIRINOX; standard FOLFIRINOX.

Publication types

Review