Adjuvant chemoradiotherapy of advanced resectable rectal cancer: results of a randomised trial comparing modulation of 5-fluorouracil with folinic acid or with interferon-alpha.

Author(s): Kornmann M, Staib L, Wiegel T, Kreuser ED, Kron M, Baumann W, Henne-Bruns D, Link KH

Affiliation(s): Department of General, Visceral, and Transplantation Surgery, University of Ulm, Steinhoevelstrasse, Ulm 89075, Germany. marko.kornmann@uniklinik-ulm.de

Publication date & source: 2010-10-12, Br J Cancer., 103(8):1163-72. Epub 2010 Sep 28.

Publication type: Randomized Controlled Trial; Research Support, Non-U.S. Gov't

BACKGROUND: Standard adjuvant chemoradiotherapy of rectal cancer still consists of 5-fluorouracil (5-FU) only. Its cytotoxicity is enhanced by folinic acid (FA) and interferon-alpha (INFalpha). In this trial, the effects of FA and IFNalpha on adjuvant 5-FU chemoradiotherapy in locally advanced rectal cancer were investigated. METHODS: Patients with R(0)-resected rectal cancer (UICC stage II and III) were stratified and randomised to a 12-month adjuvant chemoradiotherapy with 5-FU, 5-FU+FA, or 5-FU+IFNalpha. All patients received levamisol and local irradiation with 50.4 Gy. RESULTS: Median follow-up was 4.9 years (n=796). Toxicities (WHO III+IV) were observed in 32, 28, and 58% of patients receiving 5-FU, 5-FU+FA, and 5-FU+IFNalpha, respectively. No differences between the groups were observed for local or distant recurrence. Five-year overall survival (OS) rates were 60.3% (95% confidence interval (CI): 54.3-65.8), 60.4% (54.4-65.8), and 59.9% (53.0-66.1) for 5-FU, 5-FU+FA, and 5-FU+IFNalpha, respectively. A subgroup analysis in stage II (pT3/4pN0) disease (n=271) revealed that the addition of FA tended to reduce the 5-year local recurrence (LR) rate by 55% and increase recurrence-free survival and OS rates by 12 and 13%, respectively, relative to 5-FU alone. CONCLUSIONS: Interferon-alpha cannot be recommended for adjuvant chemoradiotherapy of rectal cancer. In UICC stage II disease, the addition of FA tended to lower LR and increased survival. The addition of FA to 5-FU may be an effective option for adjuvant chemoradiotherapy of UICC stage II rectal cancer.