title: Pharmacology of the paclitaxel-cisplatin, gemcitabine-cisplatin, and paclitaxel-gemcitabine combinations in patients with advanced non-small cell lung cancer.
abstract: OBJECTIVE
  To compare the pharmacology of the paclitaxel-cisplatin, gemcitabine-cisplatin and paclitaxel-gemcitabine combinations in patients with advanced non-small cell lung cancer (NSCLC).
  
  
  METHODS
  Twenty-four chemo-naive patients with advanced NSCLC were randomized to receive one of the three regimens. Plasma pharmacokinetics and pharmacologic parameters in mononuclear cells were compared and related to toxicity and efficacy.
  
  
  RESULTS
  Pharmacological parameters of gemcitabine and cisplatin were not influenced by the combination with one of the other agents, while the paclitaxel clearance was significantly lower for the combination with cisplatin as compared to gemcitabine (P=0.024). The percentage decrease in platelets was significantly higher for the gemcitabine combinations (P=0.004) and related to the dFdCTP-Cmax (P=0.030). Pharmacologic parameters were not related to response or survival.
  
  
  CONCLUSIONS
  Gemcitabine and cisplatin pharmacology were not influenced by the combination with one of the other agents, while paclitaxel has a lower clearance in combination with cisplatin as compared to gemcitabine.
authors.affiliation: Department of Medical Oncology, VU University Medical Center, PO Box 7057, 1007 MB, Amsterdam, The Netherlands.
authors.forename: J R
authors.initials: JR
authors.lastname: Kroep
authors.forename: E F
authors.initials: EF
authors.lastname: Smit
authors.forename: G
authors.initials: G
authors.lastname: Giaccone
authors.forename: K
authors.initials: K
authors.lastname: Van der Born
authors.forename: J H
authors.initials: JH
authors.lastname: Beijnen
authors.forename: C J
authors.initials: CJ
authors.lastname: Van Groeningen
authors.forename: W J F
authors.initials: WJ
authors.lastname: Van der Vijgh
authors.forename: P E
authors.initials: PE
authors.lastname: Postmus
authors.forename: H M
authors.initials: HM
authors.lastname: Pinedo
authors.forename: G J
authors.initials: GJ
authors.lastname: Peters
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D019540:Area Under Curve; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000378:metabolism; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D004347:Drug Interactions; D005260:Female; D006207:Half-Life; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D017239:Paclitaxel / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D000093542:Gemcitabine
chemical_list: D003841:Deoxycytidine; D017239:Paclitaxel; D002945:Cisplatin; D000093542:Gemcitabine