Neoadjuvant FOLFOXIRI Demonstrates Favorable Safety and Deliverability in High-Risk Locally Advanced Colon Cancer
Key Clinical Takeaways
- Design/Population: In a single-arm, open-label trial, 72 patients with high-risk, locally advanced colon cancer (T4a/b and/or N2, no metastases) received 4 cycles of neoadjuvant FOLFOXIRI followed by surgery and adjuvant CAPOX, capecitabine, or observation.
- Key Outcomes: 80.6% completed all 4 cycles; TRG 0–2 was achieved in 86.9%, R0 resection in 100%, and pathologic complete response in 3.3%. Grade 3/4 adverse events occurred in 51.4%, most commonly nausea (86.1%). Two-year recurrence rate was 17.2%.
- Clinical Relevance: Neoadjuvant FOLFOXIRI showed high resectability and tumor regression with acceptable safety, supporting further evaluation in larger, long-term trials for locally advanced colon cancer.
According to results from a prospective phase 2 trial, neoadjuvant oxaliplatin, irinotecan, and fluorouracil (FOLFOXIRI) demonstrated favorable safety, deliverability, and encouraging clinical activity in patients with high-risk locally advanced colon cancer.
“The efficacy and safety of FOLFOXIRI as neoadjuvant chemotherapy in locally advanced colon cancer remain unclear,” stated Yu-Wen Zhou, MD, PhD, of West China Hospital, Chengdu, and coauthors. The investigators sought to “evaluate the safety and deliverability of neoadjuvant chemotherapy with this 3-drug–intensity regimen.”
In this single-arm, open-label trial, 72 patients with T4a/b (n = 65) and/or N2 fused lymph nodes (n = 66) and no distant metastases received 4 cycles of neoadjuvant FOLFOXIRI, followed by surgical resection and adjuvant chemotherapy with either capecitabine plus oxaliplatin (CAPOX) for 2 to 5 cycles, single-agent capecitabine for 5 cycles, or observation. Primary end points included safety, deliverability, and the rate of tumor regression grade (TRG) 0–2.
At analysis, 80.6% of patients completed all 4 cycles of FOLFOXIRI. A clinical complete response was achieved in 1 patient, and a clinical partial response was observed in 27 patients. The most frequently reported adverse event was nausea (86.1%), while grade 3/4 adverse events occurred in 51.4% of patients. R0 resection was achieved in all 61 patients who underwent surgery, and the TRG 0–2 rate was 86.9%. The pathologic complete response rate was 3.3%, with pT0–2 and pN0 observed in 18% and 67.2% of patients, respectively. Perioperative complications led to prolonged hospitalization in 3 patients and no deaths occurred within 30 or 90 days after surgery. The 2-year tumor recurrence rate was 17.2%.
As Dr Zhou et al concluded, this “FOLFOXIRI regimen has preferable safety and deliverability…[however] longer follow-up and larger clinical studies are needed to validate its efficacy superiority.”
Source:
Zhou YW, Wei GX, Chen XR, et al. Neoadjuvant chemotherapy with FOLFOXIRI for high-risk relapsed locally advanced colon cancer: A single-arm phase II trial. ESMO Open. Published online: August 20, 2025. doi:10.1016/j.esmoop.2025.105551
