FOLFIRINOX: A Comprehensive Review of Pharmacology, Clinical Efficacy, and Therapeutic Guidelines

1. Introduction to FOLFIRINOX

FOLFIRINOX is a multi-agent chemotherapy regimen, an acronym derived from its constituent drugs: FOLinic acid (also known as leucovorin), Fluorouracil (5-FU), IRINotecan, and OXaliplatin.[1] This intensive combination therapy has emerged as a pivotal treatment strategy in modern oncology, particularly for aggressive gastrointestinal malignancies.

The introduction of FOLFIRINOX marked a significant advancement in cancer care, most notably in the first-line management of metastatic pancreatic cancer. The landmark ACCORD 11 / PRODIGE 4 trial demonstrated its superiority over the previous standard of care, gemcitabine monotherapy, by substantially improving overall survival.[3] Beyond pancreatic cancer, the FOLFIRINOX combination, often termed FOLFOXIRI in the context of colorectal cancer, has also found utility in treating advanced colorectal cancer and has shown promise in other gastrointestinal neoplasms, such as gallbladder cancer in preliminary studies.[7]

The rationale behind combining these four specific agents lies in their distinct mechanisms of action, which collectively target multiple critical pathways involved in cancer cell proliferation, DNA replication, and cell survival. This multi-pronged attack is designed to maximize cytotoxic efficacy, potentially circumvent intrinsic or acquired drug resistance, and thereby improve clinical outcomes such as tumor response rates and patient survival.[3]