Adjuvant radiochemotherapy in resectable stage II, III rectal cancer: Results of the FOGT-2 trial

Abstract

3608 Background: In this phase III trial (FOGT-2) we studied whether one of the 5-FU modulations with either folinic acid (FA) or Interferon alpha-2a (IFNa) increased overall survival compared to the standard treatment in R0-resected rectal cancer, 5-fluorouracil (5-FU) plus levamisole (LEV) for 12 months, plus postoperative radiotherapy (RT). Methods: From 7/92 to 5/03 793 patients with resected rectal cancer stages UICC II (267 pts.) and UICC III (526 pts.) were randomized into three arms and stratified (N-stage, centers). After a postoperative loading course with 5-FU [450mg/ m2 d1–5 (arms A and C)] or 5-FU [450mg/m2 plus folinic acid (Rescuvolin, medac, Hamburg, Germany), 200 mg/ m2 d1–5 (arm B)], LEV was administered orally at 150 mg/d d1–3, q every 2 weeks. 4wks later treatment was continued weekly for up to 52 wks. RT was given over a 6-wks postoperative period in a 3-field technique up to a dose of 45–50,4 Gy in 1,8 Gy fractions 5x/wk with a 20% dose reduction of 5-FU. Arm A (280 pts.) was treated with 5-FU i.v. (450 mg/ m2 at d 1, q 1 w) plus LEV. 5-FU plus LEV was modulated in arm B (291 pts.) with FA (200mg/ m2 d1, q 1 w), and in arm C (222 pts.) with IFNa at 6 million units 3x/week, q 1 w. Arm C was closed early due to toxicity. Results: Toxic events WHO3,4, mainly diarrhea, leukopenia, occurred in 36% of all pts. (A, 31%, B,27%, C, 55%). Discontinuance rates were 34% (all), 33% (A), 31% (B), 39% (C). 80% of all pts. received treatment for at least 6 months. Overall relapse rates were 37% (all), 39% (A), 35% (B) and 37% (C). Tumors relapsed either locally (all: 6%; A, C:6%, B:5%) or distant (all: 26%; A: 27%, B, C: 26%) or both locally and distant (all: 5%; A: 6%, B, C: 5%). Death rates were 32% (all), 33% (A), 28% (B), and 34% (C), with no significant difference among arms in Kaplan-Meier analysis. There were 2 toxic deaths (A, C). Conclusions: Adjuvant postoperative radio-/chemotherapy with 5-FU +/- FA plus LEV for 12 months in more than 700 patients is safe, well tolerated and shows low local recurrence rates. IFNa-modulation of 5-FU (plus LEV) adds toxicity without therapeutic benefit. No significant financial relationships to disclose.