title: Phase I trial of weekly docetaxel with a 4-weekly cisplatin administration in patients with advanced gastric carcinoma.
abstract: The docetaxel-cisplatin combination is active against several tumors including gastric cancer but it is followed by severe myelosuppression. Recent experience with weekly taxanes has demonstrated a mild myelotoxicity with high dose intensity. We investigated in a phase I study a weekly schedule of docetaxel on days 1, 8 and 15 and cisplatin on day 1 every 4 weeks in 19 patients with advanced gastric cancer with no prior chemotherapy. Cohorts of patients were treated with escalating doses of docetaxel (starting dose 30 mg/m(2) per week and increments of 10 mg/m(2) per week) and cisplatin (starting dose 70 mg/m(2) and increments of 5 mg/m(2)). Febrile neutropenia was the only dose-limiting event occurring in four (20%) patients; the dose-limiting toxicity was reached at dose level three (docetaxel 40 mg/m(2) per week and cisplatin 75 mg/m(2)). The maximum-tolerated dose was 40 mg/m(2) per week for docetaxel and 70 mg/m(2) every 4 weeks for cisplatin. Grade 3/4 neutropenia occurred in six patients (30%); early death occurred in one patient with septic shock because of neutropenia and another with acute coronary ischemia. Two (11%) complete and two (11%) partial responses were documented (ORR 22%; 95% CI 3-39%), with a median response duration of 5 months and median time to progression of 7 months. In conclusion, the combination of weekly docetaxel plus cisplatin is feasible with moderate toxicity and merits further investigation in phase II studies in advanced gastric cancer.
authors.affiliation: Medical Oncology Unit, Laikon General Hospital, Athens University School of Medicine, Athens, Greece. r-e-poly@hol.gr
authors.forename: Aristides
authors.initials: A
authors.lastname: Polyzos
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Syrigos
authors.forename: John
authors.initials: J
authors.lastname: Stergiou
authors.forename: Christos
authors.initials: C
authors.lastname: Panopoulos
authors.forename: Anna
authors.initials: A
authors.lastname: Potamianou
authors.forename: Lambros
authors.initials: L
authors.lastname: Vamvakas
authors.forename: Vassilios
authors.initials: V
authors.lastname: Georgoulias
mesh_terms: D000328:Adult; D000368:Aged; D000740:Anemia / Q000139:chemically induced / Q000145:classification; D000970:Antineoplastic Agents / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002945:Cisplatin / Q000008:administration & dosage; D000077143:Docetaxel; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009503:Neutropenia / Q000139:chemically induced / Q000145:classification; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000401:mortality; D015996:Survival Rate; D043823:Taxoids / Q000008:administration & dosage
chemical_list: D000970:Antineoplastic Agents; D043823:Taxoids; D000077143:Docetaxel; D002945:Cisplatin