Bimonthly 24 h Infusion of High-Dose 5-Fluorouracil vs EAP Regimen in Patients with Advanced Gastric Cancer: A Randomized Phase II Study

Background : To investigate the activity and toxicity of high dose (HD) infusional 5-FU in comparison to EAP regimen as first-line chemotherapy in patients with advanced gastric cancer. Patients and methods : Histologically confirmed measurable advanced gastric cancer, age < 72 yr, ECOG performance status 0–2, no prior chemo- and radiotherapy, adequate organ functions. Treatment: EAP arm: doxorubicin (40 mg/m 2 ), etoposide (360 mg/m 2 ), and cisplatin (80 mg/m 2 ) every 28 d; HD 5-FU arm: 5-FU 2.6 g/m 2 24 h infusion, biweekly. Results : Sixty patients were randomized. Patient characteristics (arms EAP/HD 5-FU): Median age 57/55 yr, median PS 1/1, LAD (patients) 3/8, M1 (patients) 27/22. Median number of cycles (range): EAP arm 4 (2–8), HD 5-FU arm 2 (1–8). Worst toxicity per cycle (grade 3 and 4 in%): Neutropenia 20/3, thrombocytopenia 9/0, anemia 9/13, diarrhea 3/10, nausea 17/7, vomiting 10/0 for EAP and HD 5-FU arms, respectively. All patients were eligible for response in both arms. Confirmed response rate (95%CI): EAP arm 34% [16–50%]/HD 5-FU arm 10% (0–21%), no change: 46/40%, progression of disease: 20/50, respectively. Overall survival (range): EAP arm A 7 mo [3–27], HD 5-FU arm 6 mo (4–25). Conclusions : Infusional HD 5-FU showed a low incidence of severe toxicity. But given the low efficacy of 5-FU in the dosage we applied in the study, it cannot be recommended as a single treatment for further studies. Assessment of higher dose intensity and/or dose density of 5-FU, with introduction of other active drugs in combination, could be an option for further studies.