A multicenter phase II study of neoadjuvant FOLFOXIRI followed by concurrent capecitabine and radiotherapy for high risk rectal cancer: A final report

Abstract

Background: We investigated the feasibility of adding FOLFOXIRI to neoadjuvant che-moradiotherapy for patients (pts) with high risk rectal adenocarcinoma (T3-4 +/-node positivity, threatened margin and/or sphincter involvement). Methods: Eligible patients were treated with 4 cycles of modified FOLFOXIRI (D1: CPT-11 165mg/m2, D1: oxaliplatin 85mg/m2, D1-2 200mg/m2 leucovorin, D1-2 5FU 400mg/m2 30min, then D1-2 5FU 600mg/m2 over 22hrs, with GCSF support), followed by capecitabine (825mg/m2 b.d) given concurrently during pre-operative radiotherapy (CRT, 50.4 Gy, 28 fr, 5 wks). Pts underwent surgery at planned 8-10 weeks after CRT, followed by adjuvant chemo. The primary endpoints were pathologic complete response rate (pCR) and objective response rate (ORR, RECIST ver 1.1). Results: 40 eligible pts were enrolled (median age 60 yrs; male:female=82%:18%), 1 pt was excluded before starting treatment. Baseline stage distribution was stage II (10.2%), IIIB (64.1%) and IIIC (25.7%). Of the 39 pts evaluated for response (ITT), ORR to FOLFOXIRI was 38.5% (15 PRs, 24SDs); ORRtoCRT was 64.1% (25 PRs, 9 SDs, 1 PD, 4NA). Total of 28 pt (out of 38 evaluated, 73.7%) had a reduced overall TNM stage. Ofthe 27pts who underwent surgery (18.5% had permanent stoma), pCR rate was 25.9%, 26 pts had negative and 1 pt had close margin, respectively. At median follow-up of 30.2 months, the 2-yr overall survival and relapse-free rates were 79.3% and 82.8%, respectively. The top three most common grade 3-4 toxicities: (1) To FOLFOXIRI were diarrhea (12%), neutropenia (7.7%) and hyponatremia (5.1%); (2) To CRT - diarrhea (2.5%), RT-dermatitis (2.5%) and rectal hemorrhage (2.5%). No treatment-related deaths or perioperative mortality were encountered. Conclusions: Insummary, neoadjuvant FOLFOXIRI followed byCape-RT for high risk rectal cancer is feasible and the pCR rate compares favorably with the historic rate of 13.8% with CRT alone (Yeung et al. Hong Kong Med J 2016;22) This strategy is being evaluated in a randomized study.