title: A phase I dose finding study of a biweekly schedule of a fixed dose of cisplatin with increasing doses of paclitaxel in patients with advanced esophageal cancer.
abstract: We performed a phase I study of a fixed dose of cisplatin combined with increasing doses of paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) given in a biweekly schedule to determine the maximum tolerated dose in patients with advanced esophageal cancer. The starting dose was cisplatin 60 mg/m2 and paclitaxel 100 mg/m2, given by intravenous infusion every 2 weeks. Patients were re-treated when the granulocyte counts were greater than 0.75 x 10(9)L and the platelet counts were greater than 75 x 10(9)/L. The paclitaxel dose has been escalated to 160 mg/m2 and the maximum tolerated dose has not yet been reached. At the higher dose levels, more grade 3 and 4 granulocytopenia was observed, but no patient had to be hospitalized because of febrile neutropenia. Nonhematologic toxicity was mild at all dose levels. Increasing the dose of paclitaxel from 100 mg/m2 to 160 mg/m2 leads to an approximately 50% increase in the dose intensity, as calculated in milligrams per square meter per week (mg/m2/wk) over six cycles. Of the 31 patients evaluable for response, 17 (55%) achieved either a partial or a complete response. In conclusion, biweekly administration of cisplatin and paclitaxel, with re-treatment at a granulocyte level greater than 0.75 x 10(9)/L, is feasible and well tolerated, and has a promising response rate in patients with advanced esophageal cancer. Further accrual is ongoing to determine the maximum tolerated dose of this schedule.
authors.affiliation: Department of Medical Oncology, University Hospital Rotterdam-Dijkzigt, Rotterdam, The Netherlands.
authors.forename: A
authors.initials: A
authors.lastname: van der Gaast
authors.forename: T C
authors.initials: TC
authors.lastname: Kok
authors.forename: R
authors.initials: R
authors.lastname: Vos
authors.forename: L
authors.initials: L
authors.lastname: Kerkhofs
authors.forename: T A
authors.initials: TA
authors.lastname: Splinter
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use / Q000633:toxicity*; D002945:Cisplatin / Q000008:administration & dosage / Q000633:toxicity*; D004938:Esophageal Neoplasms / Q000188:drug therapy*; D005260:Female; D006402:Hematologic Diseases / Q000139:chemically induced; D006801:Humans; D008297:Male; D008875:Middle Aged; D017239:Paclitaxel / Q000008:administration & dosage / Q000633:toxicity*; D016896:Treatment Outcome
chemical_list: D017239:Paclitaxel; D002945:Cisplatin