title: Pilot study of UFT combined with 5 consecutive days cisplatin in non-small cell lung cancer.
abstract: Combined use of 5-fluorouracil (5-FU) and cisplatin has proven to have synergistic effects in many experimental systems and clinical studies. UFT, an oral preparation of uracil and tegafur in a 4:1 molar ratio, was reported to have enhanced activity as compared with 5-FU or tegafur alone against various human tumors. Based on those results, we conducted a pilot study to confirm the feasibility and antitumor effect of UFT in combination with cisplatin in patients with advanced non-small cell lung cancer (NSCLC). UFT was orally administered at a dose of 400 mg/m2 according to a protocol for step-wise prolongation of the administration period, such as days 1-14 in step I, days 1-21 in step II, days 1-28 in step III. During to course, cisplatin was administered at a fixed dose of 20 mg/m2/day on days 8 through 12. The course was repeated every 4 weeks. Numbers of patients enrolled in steps I, II, III were six, ten and six (a total of 22), respectively. There were three females and 19 males, PS scored 0/1/2 = 7/14/1, stage IIIA/IIIB/IV = 3/8/11. Adenocarcinoma/squamous cell carcinoma/large cell carcinoma = 11/7/4, and median age 68 (range 52-79). All 22 patients were evaluable for toxicity, and 21 for efficacy. Compliance of UFT declined as the administration period of UFT was prolonged. In step I, one patient had grade 3 toxicity of each neutropenia, thrombocytopenia, nausea/vomiting and diarrhea. In step II, grade 3, 4 neutropenia was seen in four patients, grade 3 thrombocytopenia and anorexia in one patient, and grade 3 nausea/vomiting in four patients. In step III, there was grade 3 neutropenia in two patients and grade 3 anorexia in one patient. All other toxicities were mild. The overall response rate was 38% (one CR and 7 PR, 95% C.I.: 21-59%). Combination therapy with oral UFT and 5-day infusion of cisplatin is feasible with substantial antitumor effect against advanced NSCLC. Since UFT compliance decreased in step III (no patient in step III received > 2 courses of treatment), we considered the step II schedule to be worth for further evaluation in a combination phase II study.
authors.affiliation: Department of Respiratory Medicine, Miyagi Cancer Center, Natori, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Koinumaru
authors.forename: T
authors.initials: T
authors.lastname: Matsuda
authors.forename: J
authors.initials: J
authors.lastname: Saitoh
authors.forename: Y
authors.initials: Y
authors.lastname: Nakai
mesh_terms: D000284:Administration, Oral; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy*; D002945:Cisplatin / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004338:Drug Combinations; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D010349:Patient Compliance; D010865:Pilot Projects; D005641:Tegafur / Q000008:administration & dosage; D014498:Uracil / Q000008:administration & dosage
chemical_list: D004338:Drug Combinations; C096910:UFT(R) drug; D005641:Tegafur; D014498:Uracil; D002945:Cisplatin