title: Paclitaxel administered over 3 h followed by cisplatin in patients with advanced head and neck squamous cell carcinoma: a clinical phase I study.
abstract: We have performed a clinical phase I trial of a combination treatment with paclitaxel given as 3-hour infusion and cisplatin to determine the maximum tolerated dose and the dose-limiting toxicity in patients with recurrent or metastatic squamous cell carcinoma of the head and neck. Treatment was repeated every 21 days. Doses administered ranged from 135 mg/m2 paclitaxel/75 mg/m2 cisplatin to 250 mg/m2 paclitaxel/100 mg/m2 cisplatin. Twenty-four patients have been entered into this study. The maximum tolerated dose was determined to be 225-250 mg/m2 paclitaxel/100 mg/m2 cisplatin. The dose-limiting toxicity of this regimen was myelosuppression (granulocytopenia). Neurosensory and neuromotor toxicity was moderate. However, analyses of threshold electrotonus studies indicated subclinical neurotoxicity in most patients. One patient receiving 200 mg/m2 paclitaxel/100 mg/m2 cisplatin developed grade 3 motor-neurotoxicity. Orthostatic hypotension was observed in 8 patients receiving doses of 200 mg/m2 paclitaxel/100 mg/m2 cisplatin or higher. Objective responses were observed at paclitaxel 175 mg/m2/ cisplatin 100 mg/m2 (n = 5; complete response in 1 patient), paclitaxel 200 mg/ m2/cisplatin 100 mg/m2 (n = 3; partial response in 3 patients) and at paclitaxel 225 mg/m2/cisplatin 100 mg/m2 (n = 8; partial response in 1 patient). Eleven additional patients had stable disease. We conclude that paclitaxel administered as a 3-hour infusion followed by cisplatin is an active regimen in advanced head and neck cancer and that orthostatic hypotension may be a potentially significant clinical toxicity.
authors.affiliation: First Department of Medicine, Technische Universität München, Germany.
authors.forename: T
authors.initials: T
authors.lastname: Schilling
authors.forename: B
authors.initials: B
authors.lastname: Heinrich
authors.forename: R
authors.initials: R
authors.lastname: Kau
authors.forename: M
authors.initials: M
authors.lastname: Herzog
authors.forename: S
authors.initials: S
authors.lastname: Quasthoff
authors.forename: K
authors.initials: K
authors.lastname: Diergarten
authors.forename: J
authors.initials: J
authors.lastname: Rastetter
authors.forename: A R
authors.initials: AR
authors.lastname: Hanauske
mesh_terms: D000328:Adult; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy*; D002945:Cisplatin / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D006258:Head and Neck Neoplasms / Q000188:drug therapy*; D006410:Hematopoiesis / Q000187:drug effects; D006801:Humans; D007024:Hypotension, Orthostatic / Q000139:chemically induced; D007262:Infusions, Intravenous; D007970:Leukopenia / Q000139:chemically induced; D008297:Male; D008875:Middle Aged; D009503:Neutropenia / Q000139:chemically induced; D017239:Paclitaxel / Q000008:administration & dosage; D017933:Peripheral Nervous System / Q000187:drug effects; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced; D016896:Treatment Outcome
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D017239:Paclitaxel; D002945:Cisplatin