title: Docetaxel and vinorelbine in recurrent head and neck cancer: pharmacokinetic and clinical results.
abstract: The purpose of this study was to evaluate pharmacokinetic parameters, efficacy, and toxicity of a combination of docetaxel (DTX) and vinorelbine (VNB) in recurrent heavily pretreated squamous cell head and neck cancer. Twenty-nine patients previously treated with concomitant chemoradiotherapy (n = 14), surgery plus radiotherapy (n = 13), surgery+concomitant chemoradiotherapy (n = 1) and radiotherapy alone (n = 1) were enrolled; 9 patients had received 1 or more courses of palliative chemotherapy. Twenty-one patients had a local-regional recurrence, and 8 patients had metastases. The doses were 80 mg/m2 for DTX and 20 mg/m2 for VNB on day 1 every 21 days for a maximum of 6 cycles. Pharmacokinetic evaluations were performed on 24 patients; in a group of 12 patients, VNB administration immediately followed DTX infusion (schedule A), and in 12 patients VNB administration was immediately followed by DTX infusion (schedule B). Twenty-nine patients received a total of 137 cycles (median per patient, 5). Neutropenia was the most frequent and severe side effect (grade IV in 79%; grade III in 21%). Grade IV (7%) and III (14%) infections were observed in the first 12 patients; ciprofloxacin prophylaxis in the following 17 patients reduced the severe toxicity to 0%. The overall response rate was 49%, which included 3 of 29 complete responses (10%) and 11 of 29 partial responses (38%). Median complete and partial response durations were 20+ and 5.5 months, respectively. Overall median survival was 10 months (range, 2-30+). The mean values of area under the curve, mean residence time (MRT), and C(max) of VNB were significantly lower for schedule A than for schedule B. The mean values of VNB clearance were significantly higher for schedule A than for schedule B. Neutrophil count at the nadir was much lower for patients receiving schedule B. The DTX-VNB combination is effective in heavily pretreated patients with a short-lasting manageable toxicity. Pharmacokinetic evaluations suggested that the sequence DTX --> VNB is safer than the sequence VNB --> DTX.
authors.affiliation: Medical Oncology Department, San Giovanni Antica Sede Hospital, Torino, Italy.
authors.forename: Mario
authors.initials: M
authors.lastname: Airoldi
authors.forename: Luigi
authors.initials: L
authors.lastname: Cattel
authors.forename: Sara
authors.initials: S
authors.lastname: Marchionatti
authors.forename: Valeria
authors.initials: V
authors.lastname: Recalenda
authors.forename: Fulvia
authors.initials: F
authors.lastname: Pedani
authors.forename: Valentina
authors.initials: V
authors.lastname: Tagini
authors.forename: Cesare
authors.initials: C
authors.lastname: Bumma
authors.forename: Fabio
authors.initials: F
authors.lastname: Beatrice
authors.forename: Giovanni
authors.initials: G
authors.lastname: Succo
authors.forename: Anna
authors.initials: A
authors.lastname: Maria Gabriele
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D019540:Area Under Curve; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy*; D000077143:Docetaxel; D005260:Female; D006258:Head and Neck Neoplasms / Q000188:drug therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy*; D012074:Remission Induction; D016019:Survival Analysis; D043823:Taxoids / Q000008:administration & dosage* / Q000493:pharmacokinetics; D014747:Vinblastine / Q000008:administration & dosage* / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D000077235:Vinorelbine
chemical_list: D043823:Taxoids; D000077143:Docetaxel; D014747:Vinblastine; D000077235:Vinorelbine