[Interferon-alpha in adjuvant treatment of colorectal carcinoma].

UNLABELLED

Based on preclinical and clinical studies, in this German three-arm adjuvant multicenter trial the FOGT (Forschungsgruppe Onkologie Gastrointestinale Tumoren) 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 colon cancer, 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 stage II (only T4N0M0, 63 pts.) and stage III (750 pts.) were randomized into three treatment groups and stratified according to N-stage 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 d1-5 (arm B)]. After completion of the first chemotherapy cycle LEV was administered orally at 150 mg/d d1-3, 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 (200 mg/m2 d1, q 1 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, and treatment costs and immune effects were analysed.

RESULTS

Toxic event(s) > WHO2, mainly leukopenia, diarrhea and nausea, occurred in 113 pts. (14%), in arms A (8%), B (13%) and C (32%). Discontinuance rates were 28% (all), 29% (A), 21% (B), 34% (C), but 80% of patients received > or = 6 months treatment. Overall relapse rates were 27% (all), 30% (A), 24% (B) and 28% (C). Tumors relapsed either locally (2% each) or distant (A: 22%, B: 20%, C: 22%). 4-year overall survival rates in arms A, B and C were 66%, 77%, 66%, respectively. The 4-year survival rate in arm B was significantly superior to arms A and C (p < 0.02, log-rank). There were no signs of a superior immune function in either treatment arm (skin test, proliferation, cytotoxicity, flow cytometry). Treatment costs per patient were 2,500 [symbol: see text](arm A), 3,500 [symbol: see text](arm B) or 10,850 [symbol: see text](arm C), respectively.

CONCLUSION

Adjuvant therapy with 5-FU plus FA plus LEV for 12 months is superior to the recommended standard (5-FU + LEV, 12 m). IFNa-modulation of 5-FU (plus LEV) adds toxicity and high treatment costs without therapeutic benefit.