A PHASE-II STUDY OF COMBINATION THERAPY WITH 5'-DEOXY-5-FLUOROURIDINEAND CISPLATIN IN THE TREATMENT OF ADVANCED GASTRIC-CANCER WITH PRIMARY FOCI

Background. 5'-Deoxy-5-fluorouridine (5'-DFUR, doxifluridine) is a rec ently developed prodrug of oral 5-fluorouracil (5-FU), which is used c linically in Japan for the treatment of gastric, colorectal, and breas t cancer. 5-FU has been reported to act synergistically with cisplatin (CDDP) in experimental and clinical studies. The authors conducted a multicenter Phase II study of combination therapy with 5'-DFUR and CDD P to evaluate the therapeutic usefulness of this regimen in the treatm ent of unresectable and advanced gastric cancers with primary foci. No ne of the patients had previously undergone chemotherapy. Their ages r anged from 27 to 75 years and performance status was grade 0 to 3. Met hods. 5'-DFUR (1400 mg/m2/d) was administered orally on days 1 through 4 and 15 through 18, and CDDP (80 mg/m2/d) was injected intravenously on day 5. This treatment cycle was repeated every 4 weeks. An indepen dent panel of specialists evaluated the clinical response. Results. Fi fty-one patients were studied. Clinical evaluation of response was pos sible in 43 patients who met the protocol requirements. The overall re sponse rate was 50.0% (14 of 28,95% confidence limits, 30.7%-69.4%) fo r patients with measurable lesions. The median duration of response wa s 5.2 months (156 days). The overall median survival time was 8.9 mont hs (268 days) for evaluated patients. Therapeutic toxicity of World He alth Organization (WHO) grade greater-than-or-equal-to 3 was manifeste d as anorexia and nausea or vomiting in 20.9% and 18.6% of the patient s, respectively. However myelotoxicity and nephrotoxicity of WHO grade s 3 and 4 occurred in less than 10% of the patient group. No drug-rela ted mortality occurred. Conclusions. Combined therapy with 5'-DFUR and CDDP is a safe and effective treatment regimen for advanced gastric c ancers with primary foci which stresses the patient's quality of life, especially when used in an outpatient setting.