CISPLATIN, ETOPOSIDE, AND WEEKLY HIGH-DOSE 5-FLUOROURACIL AND LEUCOVORIN INFUSION (PE-HDFL) - A VERY EFFECTIVE REGIMEN WITH GOOD PATIENTS COMPLIANCE FOR ADVANCED GASTRIC-CANCER

We have previously shown that weekly 24-hour infusion of high-dose 5-f luorouracil and leucovorin (HDFL), a regimen initially designed for th e treatment of advanced colorectal cancer, is also effective in the tr eatment of gastric cancer. This HDFL regimen is unique in that if is v irtually non-myelosuppressive, and thus provides a cornerstone on whic h ideal protocols may be developed. In this prospective phase 17 study we examined the efficacy and toxicity of PE (cisplatin, etoposide)-HD FL, a HDFL-based combination chemotherapy, in the treatment of advance d-gastric cancer. This regimen consisted of cisplatin 60 mg/m(2), i.v. , D1; etoposide 65 mg/m(2), i.v, D1-3; and 5-fluorouracil 2600 mg/m(2) plus leucovorin 300 mg/m(2), 24-hour i.v. infusion by an ambulatory i nfusion pump, D2,9,16; repeated every 4 weeks. The major eligibility c riteria of the patients included: a) a histologically confirmed, objec tively measurable, recurrent or primary inoperable gastric adenocadcin oma; b) age greater than or equal to 75 years; c) a Karnofsky performa nce status greater than or equal to 50%; d) an absolute granulocyte co unt (AGC) greater than or equal to 2000/mm(3) and a platelet count gre ater than or equal to 100,000/mm(3); e) a serum bilirubin concentratio n less than or equal to 2.0 mg/dl; f) a serum creatinine concentration less than or equal to 1.5 mg/dl; and g) a signed informed consent. Be tween March 1992 and June 1996, a total of 42 patients were enrolled o nto the study. There were 31 men and 11 women with a median age of 54 (24-75) years; these included 16 primary metastatic,3 locally advanced and inoperable, and 23 postgastrectomy recurrent gastric cancer patie nts ECOG (Eastern Cooperative Oncology Group) grade III/IV leukopenia and thrombocytopenia developed in 34.0% and 11.0% of a total of 229 co urses given, respectively. There was no treatment-related death. Four patients developed a reversible neurotoxicity; and two of them refused further chemotherapy. Among the 40 patients evaluable for responses, 9 [22.5%; 12-38%, 95% confidence interval (C.I)] patients achieved com plete remission, and 20 [50.0%; 33-67%, 95% C.I.] patients achieved pa rtial remission. The overall response rate was 72.5% [56-86%, 95% C.I. ]. The overall median survival and median time to progression of the r esponders were 10 and 7 months, respectively The overall median surviv al of the whole group was 9 months. We concluded that PE-HDFL is a hig hly effective treatment for advanced gastric cancer. The treatment-rel ated toxicity was mild and the patients' compliance was satisfactory.