Abstracts
2000 Digestive Disease Week

# 2395 Adjuvant Therapy in Colon Cancer: Results of the German Prospective, Controlled, Randomized Multicenter Trial.
Karl H. Link, Ludger Staib, Hans G. Beger, Ulm, Germany

In this multicenter German three-arm adjuvant trial we studied whether one of the 5-FU modulations with either folinic acid (FA) or Interferon alpha-2a (IFNa) is superior to the recommended standard of adjuvant treatment in R0-resected coloncancer, 5-fluorouracil (5-FU) plus levamisole (LEV) for 12 months, in terms of overall survival rates. Patients/Methods: From 7/92 to 10/99 813 patients with resected colon cancer stages T4N0M0 (63 pts.) and T1-3N1-2M0 (750 pts.) were randomized into three treatment groups and stratified according to N-stage (N0 vs. N1 vs. N2) and participating centers (64 hospitals). The patients received a postoperative loading course with 5-FU [450 mg/m2 d1-5 (arms A and C)] or 5-FU [450 mg/m2 plus folinic acid (Rescuvolin“, medac, Hamburg, Germany), 200 mg/m2 d1- (arm B)]. After completion of the first chemotherapy cycle LEV was administered orally at 150 mg/d d1-3, q every 2 weeks. After a 4-week chemotherapy-free interval the treatment was continued weekly for up to 52 weeks. The standard group, arm A (279 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 (283 pts.) with FA (200mg/m2=d1, q w), and in arm C (251 pts.) with IFNa at 6 million units 3x/week, q 1 w. Chemotherapy doses were adjusted to toxicity if toxic events >WHO 2 occurred. The patients were followed-up to determine relapse rates and - patterns and survival. Survival rates were calculated according to Kaplan-Meier. Results: Toxic event(s) >WHO2, mainly leukopenia, diarrhea and nausea, occurred in 113 pts. (14%), in arms A (7%), B (11%) and C (25.4%). Discontinuance rates were 28% (all), 29% (A), 21% (B), 34% (C). Overall relapse rates were 27% (all), 30% (A), 24% (B) and 28% (C). Tumors relapsed either locally (all: 2%; A, B, C: 2% each) or distant (all: 21%; A: 22%, B: 20%, C: 22%) or both locally and distant (all: 4%; A: 5%, B: 2%, C: 4%). 1-, 3- and 4-year overall survival rates in arms A, B and C were 93.6%, 96.5%, 96.1% (1 y), 73.8%, 80.9%, 75.5% (3 y) and 66.1%, 77.5%, 66.2% (4 y). The 4-y survival rate in arm B was significantly superior to arms A and C (p<0.02, log-rank). Conclusion: Adjuvant therapy with -FU plus FA plus LEV for12months is superior to the recommended standard (5-FU+ LEV, 12m). IFNa-modulation of 5-FU (plus LEV) adds toxicity without therapeutic benefit. *FOGT- Research Group Oncology of Gastrointestinal Tumors.