Modified FOLFIRINOX (mFOLFIRINOX) in high risk locally advanced rectal adenocarcinomas.

Abstract

108 Background: There is limited data with regard to the use of modified 5-fluoroural-leucovorin-irinotecan-oxaliplatin (mFOLFIRINOX) in enabling resection and increasing survival of locally advanced rectal adenocarcinomas (LARC) with high-risk characteristics (T4b status, signet ring histology, etc.) post standard neoadjuvant long course chemoradiation (NACTRT) or short course radiation (SCRT) and chemotherapy. Methods: Patients with LARC from January 2018 to December 2020 receiving mFOLFIRINOX (5-Fluorouracil - 1800mg/m2 over 46 hours, Leucovorin 300mg, Irinotecan 135mg/m2, oxaliplatin 65mg/m2) post NACTRT/SCRT to facilitate curative local resection were evaluated. The primary endpoint was event free survival (EFS), where event was defined as disease progression or recurrence post resection after mFOLFIRINOX. Survivals were calculated using Kaplan-Meier analysis. Results: Forty-seven patients were evaluated with a median age of 33 years (Range:18-59), 45% T4b status, 94% radiological circumferential margin (CRM) involved (79% CRM positive post NACTRT/SCRT), 43% extramural venous invasion (n=33) and 36% signet ring histology. 62% had received prior NACTRT and 38% had received SCRT with chemotherapy before receiving mFOLFIRINOX. The most common grade 3 and grade 4 treatment related side effects included diarrhoea (7%), anaemia (4%) and infections (4%). Intended duration of mFOLFIRINOX or beyond was completed in 94% of patients. 60% of patients underwent curative local resection with R0 resection rates of 100% (n=28) and pathological complete response rates of 21%. The most common surgeries done were exenterations and abdominoperineal resections in 22% and 17% patients respectively. With a median follow up of 19 months, 25 patients had recurred or progressed for a median EFS of 20 months [95% confidence interval (CI): 15-24] while median overall survival was 55 months (95% CI: 24-86). Conclusions: Locally advanced rectal cancers with high-risk characteristics are a niche group of cancers with less-than-optimal outcomes post standard neoadjuvant strategies. mFOLFIRINOX appears to be well tolerated in this cohort of patients and enables conversion to curative local resection and potentially improves survival as well.