To test if the incorporation of 5-fluorouracil (5-FU) and leucovorin in a modified etoposide, doxorubicin, cisplatin (EAP) regimen could diminish its toxicity and improve its efficacy, 18 patients with far-advanced, unresectable gastric cancer, diagnosed at National Taiwan University Hospital between January 1991 and December 1992, were treated with a FAPEL combination chemotherapy. The regimen consisted of doxorubicin 25 mg/m2 i.v. on day 1, cisplatin 60 mg/m2 i.v. infusion on day 1, etoposide 60 mg/m2/day i.v. infusion on days 1-3, 5-fluorouracil 500 mg/m2/day i.v. on days 1-3, and leucovorin 50 mg/day i.v. on days 1-3; repeated every three to four weeks. The patients included nine metastatic, six locally advanced and inoperable, and three post-gastrectomy recurrent cancer patients with median Karnofsky performance status of 60%. There were 11 men and seven women with a median age of 52.5 years. The patients tolerated the treatment toxicity relatively well and received an average of 4.3 courses of chemotherapy. Most patients completed the protocol therapy except one who refused and another who died of leucopenic sepsis. Myelosuppression was the limiting toxicity, with Eastern Cooperative Oncology Group (ECOG) grade 3-4 leucopenia developing in 35.9% and grade 3-4 thrombocytopenia developing in 11.5% of a total of 78 courses given. The overall objective response rate was 44.4% with 5.5% complete responses and 38.9% partial responses. The overall median survival was seven months (0.5-21 months). The median survival of responders and non-responders was 13 months (5-21 months) and three months (0.5-7 months), respectively.(ABSTRACT TRUNCATED AT 250 WORDS)