title: Gemcitabine and vinorelbine in recurrent head and neck cancer: pharmacokinetic and clinical results.
abstract: OBJECTIVE
  To evaluate the pharmacokinetic parameters, efficacy and toxicity of a combination of gemcitabine (GEM) and vinorelbine (VNB) in recurrent heavily pre-treated squamous cell head and neck carcinoma.
  
  
  METHODS
  Twenty-four patients previously treated with concomitant chemo-radiotherapy (n = 13), surgery plus radiotherapy (n = 10) and surgery + concomitant chemo-radiotherapy (n = 1) were enrolled; 7 patients had received one or more courses of palliative chemotherapy. Twenty patients had a local-regional recurrence and 4 patients had metastases. The doses were 1200 mg/m2 for GEM and 30 mg/m2 for VNB on days 1 and 8 every 21 days; a maximum of 6 cycles was allowed. Pharmacokinetic investigations were performed on 9 patients receiving GEM and VNB. As a PK control, a second group of 5 patients was given GEM as single agent, at the same doses and with the same i.v. infusion length.
  
  
  RESULTS
  Twenty-four patients received a total of 135 cycles (median per patient, 5). Neutropenia was the most frequent side-effect (92% of patients; grade 3-4 in 50%). The overall response rate was 25% which included 1 of 24 complete responses (4%) and 4 of 24 partial responses (21%). Responses were observed only in patients with good prognostic characteristics. The median response duration was 5.5 months (2-16 months) and the overall median survival was 9 months (range, 2-25+). Vinorelbine serum levels showed no evidence of any pharmacokinetic interaction with GEM; most of all, no rebound in VNB disposition can be produced by GEM pre-administration.
  
  
  CONCLUSIONS
  The GEM-VNB combination has a palliative role in patients with favourable characteristics; the results seem no better than those observed with VNB alone. Moreover, this drug association does not alter the pharmacokinetic profile of both drugs, also compared to GEM monotherapy.
authors.affiliation: Medical Oncology Department, San Giovanni Antica Sede Hospital, Via Cavour 31, 10123 Torino, Italy. mario.airoldi@jumpy.it
authors.forename: Mario
authors.initials: M
authors.lastname: Airoldi
authors.forename: Luigi
authors.initials: L
authors.lastname: Cattel
authors.forename: Giorgio
authors.initials: G
authors.lastname: Cortesina
authors.forename: Carlo
authors.initials: C
authors.lastname: Giordano
authors.forename: Roberto
authors.initials: R
authors.lastname: Passera
authors.forename: Fulvia
authors.initials: F
authors.lastname: Pedani
authors.forename: Silvia
authors.initials: S
authors.lastname: Novello
authors.forename: Cesare
authors.initials: C
authors.lastname: Bumma
authors.forename: Pietro
authors.initials: P
authors.lastname: Gabriele
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000378:metabolism; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D005260:Female; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000378:metabolism; D014747:Vinblastine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D000077235:Vinorelbine; D000093542:Gemcitabine
chemical_list: D003841:Deoxycytidine; D014747:Vinblastine; D000077235:Vinorelbine; D000093542:Gemcitabine