title: Phase I study of axitinib combined with paclitaxel, docetaxel or capecitabine in patients with advanced solid tumours.
abstract: BACKGROUND
  Axitinib, a potent and selective second-generation inhibitor of vascular endothelial growth factor receptors, enhanced the efficacy of chemotherapy in human xenograft tumour models. This phase I study investigated the safety, tolerability, pharmacokinetics and antitumour activity of axitinib combined with chemotherapy.
  
  
  METHODS
  A total of 42 patients with advanced solid tumours received a continuous axitinib starting dose of 5 mg twice daily (b.i.d.) plus paclitaxel (90 mg m(-2) weekly), docetaxel (100 mg m(-2) every 3 weeks) or capecitabine (1000 or 1250 mg m(-2) b.i.d., days 1-14).
  
  
  RESULTS
  Common treatment-related adverse events across all cohorts were nausea (45.2%), hypertension (45.2%), fatigue (42.9%), diarrhoea (38.1%), decreased appetite (33.3%) and hand-foot syndrome (31.0%). There was one complete response, nine partial responses and seven patients with stable disease. Ten patients (23.8%) remained on therapy for >8 months. Paclitaxel and capecitabine pharmacokinetics were similar in the absence or presence of axitinib, but docetaxel exposure was increased in the presence of axitinib. Axitinib pharmacokinetics were similar in the absence or presence of co-administered agents.
  
  
  CONCLUSIONS
  Axitinib combined with paclitaxel or capecitabine was well tolerated; no additive increase in toxicities was observed. Antitumour activity was observed for each treatment regimen and across multiple tumour types.
authors.affiliation: Department of Medical Oncology, Fox Chase Cancer Center, Philadelphia, PA, USA. L_Martin@fccc.edu
authors.forename: L P
authors.initials: LP
authors.lastname: Martin
authors.forename: M F
authors.initials: MF
authors.lastname: Kozloff
authors.forename: R S
authors.initials: RS
authors.lastname: Herbst
authors.forename: T A
authors.initials: TA
authors.lastname: Samuel
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: Y
authors.initials: Y
authors.lastname: Chen
authors.forename: J
authors.initials: J
authors.lastname: Tarazi
authors.forename: A J
authors.initials: AJ
authors.lastname: Olszanski
authors.forename: T
authors.initials: T
authors.lastname: Rado
authors.forename: A
authors.initials: A
authors.lastname: Starr
authors.forename: R B
authors.initials: RB
authors.lastname: Cohen
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000077784:Axitinib; D000069287:Capecitabine; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D000077143:Docetaxel; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000031:analogs & derivatives; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage* / Q000493:pharmacokinetics; D007191:Indazoles / Q000008:administration & dosage* / Q000493:pharmacokinetics; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology; D017239:Paclitaxel / Q000008:administration & dosage; D047428:Protein Kinase Inhibitors / Q000493:pharmacokinetics / Q000627:therapeutic use; D043823:Taxoids / Q000008:administration & dosage; D016896:Treatment Outcome
chemical_list: D007093:Imidazoles; D007191:Indazoles; D047428:Protein Kinase Inhibitors; D043823:Taxoids; D003841:Deoxycytidine; D000077143:Docetaxel; D000069287:Capecitabine; D000077784:Axitinib; D017239:Paclitaxel; D005472:Fluorouracil