Multicenter phase II study of neoadjuvant FOLFOXIRI followed by concurrent chemoradiotherapy in Chinese patients with high-risk rectal cancer.

We investigated the feasibility of adding neoadjuvant FOLFOXIRI to chemoradiotherapy (CRT) in Chinese patients with high-risk, locally advanced rectal adenocarcinoma (LARC) and examined the prognostic significance of IGF2 and L1CAM expression. Eligible patients had non-metastatic, T3/T4 disease with or without nodal involvement, threatened circumferential resection margin (CRM) and/or sphincter involvement, received 4 cycles of a modified FOLFOXIRI regimen, followed by CRT, surgery, then adjuvant chemotherapy. Co-primary endpoints were objective response rate (ORR) and pathologic complete response rate (pCR). Secondary endpoints included overall survival (OS), relapse-free survival (RFS) and safety.

Archival biopsies were analyzed for IGF2 and L1CAM expression using immunostaining. Forty patients were enrolled with median age of 60 years and median follow up of 72.7 months. The ORR of FOLFOXIRI and CRT was 30.8% and 64.1%, respectively in 39 patients evaluated, 71.8% of them exhibiting TNM downstaging. For the entire cohort, the pCR rate was 20.5% and CRM was negative in 30 patients.

The 3-year and 5-year OS were 79.5% and 59.5%, respectively. The 3-year RFS was 72.4%. Grade 3-4 toxicities to FOLFOXIRI were diarrhea (13%), neutropenia (8%), and vomiting (5%). Grade 3-4 toxicities to CRT were diarrhea (3%), rectal hemorrhage (3%), and sexual dysfunction (3%).

High IGF2 expression was negatively correlated with disease-free survival (P = .0176) but not OS. Neoadjuvant modified FOLFOXIRI followed by concurrent capecitabine-RT and surgery was effective with manageable toxicities in Chinese patients with high risk LARC. Exploratory analyses showed that IGF2 expression may be a negative prognostic factor in LARC. (NCT01941641).