title: Phase I trial of axitinib combined with platinum doublets in patients with advanced non-small cell lung cancer and other solid tumours.
abstract: BACKGROUND
  This phase I dose-finding trial evaluated safety, efficacy and pharmacokinetics of axitinib, a potent and selective second-generation inhibitor of vascular endothelial growth factor receptors, combined with platinum doublets in patients with advanced non-small cell lung cancer (NSCLC) and other solid tumours.
  
  
  METHODS
  In all, 49 patients received axitinib 5 mg twice daily (b.i.d.) with paclitaxel/carboplatin or gemcitabine/cisplatin in 3-week cycles. Following determination of the maximum tolerated dose, a squamous cell NSCLC expansion cohort was enroled and received axitinib 5 mg b.i.d. with paclitaxel/carboplatin.
  
  
  RESULTS
  Two patients experienced dose-limiting toxicities: febrile neutropenia (n=1) in the paclitaxel/carboplatin cohort and fatigue (n=1) in the gemcitabine/cisplatin cohort. Common nonhaematologic treatment-related adverse events were hypertension (36.7%), diarrhoea (34.7%) and fatigue (28.6%). No grade ≥3 haemoptysis occurred among 12 patients with squamous cell NSCLC. The objective response rate was 37.0% for patients receiving axitinib/paclitaxel/carboplatin (n=27) and 23.8% for patients receiving axitinib/gemcitabine/cisplatin (n=21). Pharmacokinetics of axitinib and chemotherapeutic agents were similar when administered alone or in combination.
  
  
  CONCLUSIONS
  Axitinib 5 mg b.i.d. may be combined with standard paclitaxel/carboplatin or gemcitabine/cisplatin regimens without evidence of overt drug-drug interactions. Both combinations demonstrated clinical efficacy and were well tolerated.
authors.affiliation: Section of Oncology/Hematology, Ingalls Hospital, Harvey, IL, USA. mfkozloff@aol.com
authors.forename: M F
authors.initials: MF
authors.lastname: Kozloff
authors.forename: L P
authors.initials: LP
authors.lastname: Martin
authors.forename: M
authors.initials: M
authors.lastname: Krzakowski
authors.forename: T A
authors.initials: TA
authors.lastname: Samuel
authors.forename: T A
authors.initials: TA
authors.lastname: Rado
authors.forename: E
authors.initials: E
authors.lastname: Arriola
authors.forename: J
authors.initials: J
authors.lastname: De Castro Carpeño
authors.forename: R S
authors.initials: RS
authors.lastname: Herbst
authors.forename: J
authors.initials: J
authors.lastname: Tarazi
authors.forename: S
authors.initials: S
authors.lastname: Kim
authors.forename: B
authors.initials: B
authors.lastname: Rosbrook
authors.forename: M
authors.initials: M
authors.lastname: Tortorici
authors.forename: A J
authors.initials: AJ
authors.lastname: Olszanski
authors.forename: R B
authors.initials: RB
authors.lastname: Cohen
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000077784:Axitinib; D016190:Carboplatin / Q000008:administration & dosage; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000473:pathology; D002945:Cisplatin / Q000008:administration & dosage; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage* / Q000493:pharmacokinetics; D007191:Indazoles / Q000008:administration & dosage* / Q000493:pharmacokinetics; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy / Q000473:pathology; D017239:Paclitaxel / Q000008:administration & dosage; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage / Q000493:pharmacokinetics; D016896:Treatment Outcome
chemical_list: D007093:Imidazoles; D007191:Indazoles; D047428:Protein Kinase Inhibitors; D016190:Carboplatin; D000077784:Axitinib; D017239:Paclitaxel; D002945:Cisplatin