79OA 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 chemoradiotherapy 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, 24 SDs); ORR to CRT 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. Of the 27 pts 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 In summary, neoadjuvant FOLFOXIRI followed by Cape-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. Clinical trial identification NCT01941641. Legal entity responsible for the study The Chinese University of Hong Kong. Funding Hong Kong Research Grant Council General Research Fund 471613. Disclosure All authors have declared no conflicts of interest.