title: Phase I study of a biweekly schedule of a fixed dose of cisplatin with increasing doses of paclitaxel in patients with advanced oesophageal cancer.
abstract: We performed this dose-finding study with a fixed dose of cisplatin and increasing doses of paclitaxel given every 2 weeks to determine the maximum tolerable dose of this schedule. Sixty-four patients with advanced oesophageal cancer were treated with a cisplatin dose of 60 mg m(-2) and increasing doses of paclitaxel from 100 mg m(-2) up to 200 mg m(-2) both administered over 3 h for a maximum of six cycles in patients with stable disease or eight cycles in responding patients. Patients were retreated when the granulocytes were > 0.75 x 10(9) l(-1) and the platelets > 75 x 10(9) l(-1). The dose of paclitaxel could be increased to 200 mg m(-2) without encountering dose limiting haematological toxicity. At the dose levels 190 mg m(-2) and 200 mg m(-2) of paclitaxel cumulative sensory neurotoxicity became the dose-limiting toxicity. The dose intensity of paclitaxel calculated over six cycles rose from 50 mg m(-2) per week to 85 mg m(-2) per week. Only three episodes of granulocytopenic fever were encountered out of a total of 362 cycles of treatment. Of the 59 patients evaluable for response, 31 (52%) had a partial or complete response. In a biweekly schedule with a fixed dose of 60 mg m(-2) cisplatin it is possible to increase the dose of paclitaxel to 180 mg m(-2). At higher dose levels, neurotoxicity becomes the dose-limiting toxicity. The observed response rate warrants further investigation 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: L
authors.initials: L
authors.lastname: Kerkhofs
authors.forename: P D
authors.initials: PD
authors.lastname: Siersema
authors.forename: H W
authors.initials: HW
authors.lastname: Tilanus
authors.forename: T A
authors.initials: TA
authors.lastname: Splinter
mesh_terms: D000328:Adult; D000368:Aged; D000380:Agranulocytosis / Q000139:chemically induced; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002277:Carcinoma / Q000188:drug therapy*; D002945:Cisplatin / Q000008:administration & dosage* / Q000009:adverse effects; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004938:Esophageal Neoplasms / Q000188:drug therapy*; D005260:Female; D006801:Humans; D007970:Leukopenia / Q000139:chemically induced; D008297:Male; D008875:Middle Aged; D009422:Nervous System Diseases / Q000139:chemically induced; D017239:Paclitaxel / Q000008:administration & dosage* / Q000009:adverse effects; D013921:Thrombocytopenia / Q000139:chemically induced
chemical_list: D017239:Paclitaxel; D002945:Cisplatin