folfox

Overview

FOLFOX is a multi-drug chemotherapy regimen combining oxaliplatin (a platinum-based DNA crosslinker), leucovorin (folinic acid, a folate that potentiates 5-FU), and fluorouracil (5-FU, a pyrimidine antimetabolite that inhibits thymidylate synthase TYMS and incorporates into RNA/DNA). It is a standard systemic regimen for colorectal and rectal cancers. In the neoadjuvant rectal-cancer setting, FOLFOX provides cytotoxic systemic coverage that complements the local effects of short-course radiotherapy (SCRT), and is being evaluated in combination with checkpoint blockade (zimberelimab) and adenosine-receptor inhibition (etrumadenant) to create a multi-mechanism strategy for achieving pathological complete response (pCR).

Evidence in the corpus

  • The ROBIN ImmunoRad MCT2 trial (NCT05024097, Phase I/II) at Weill Cornell and 9 international co-enrolling centers is studying SCRT + etrumadenant + zimberelimab + FOLFOX in locally advanced rectal cancer. As of the white paper, 21 patients had been enrolled. Preliminary CR rates were 1/5 (20%) in Part I and 11/15 patients (82%) in Part II stage 1; accrual and formal efficacy evaluation were ongoing. FOLFOX serves as the cytotoxic backbone in this regimen, complementing RT’s local immune activation and the immunomodulatory agents’ systemic effects. PMID:41941260
  • The paper explicitly lists FOLFOX alongside etrumadenant and zimberelimab as part of the combination strategy that yielded the preliminary CR signal, framing radiation-immunotherapy-chemotherapy triplets as a priority direction for ROBIN ImmunoRad. PMID:41941260
  • FOLFOX is listed as a standard backbone for PDAC; the MSK 2,336-patient clinicogenomic study notes FOLFIRINOX (which incorporates FOLFOX components fluorouracil, leucovorin, and oxaliplatin plus irinotecan) was used in 38% of curated first-line PDAC patients. Chemotherapy backbone choice (FOLFIRINOX vs gemcitabine/nab-paclitaxel) was not significantly associated with OS in 304 metastatic PDAC patients PMID:39753968.

Resistance mechanisms

No resistance mechanisms reported in the corpus at this time.

Cancer types (linked)

  • READ — rectal adenocarcinoma; FOLFOX component of SCRT + etrumadenant + zimberelimab + FOLFOX in ImmunoRad MCT2 (NCT05024097).
  • PAAD — pancreatic adenocarcinoma; FOLFIRINOX (incorporates FOLFOX components) used as first-line standard in 38% of MSK PDAC cohort.

Sources

  • PMID:41941260 — Gregucci et al. 2026, Clin Cancer Res. ROBIN white paper; FOLFOX as cytotoxic backbone in ImmunoRad MCT2 radioimmunotherapy regimen for rectal cancer.
  • PMID:39753968 — Varghese et al. 2025, Nature Medicine. MSK PDAC clinicogenomic landscape; FOLFIRINOX as standard first-line PDAC backbone.

This page was processed by crosslinker on 2026-05-04.