title: Intermittent dosing of axitinib combined with chemotherapy is supported by (18)FLT-PET in gastrointestinal tumours.
abstract: BACKGROUND
  We evaluated week-on/week-off axitinib dosing plus chemotherapy in patients with gastrointestinal tumours, including tumour thymidine uptake by fluorine-18 3'-deoxy-3'-fluorothymidine positron emission tomography ((18)FLT-PET).
  
  
  METHODS
  During a lead-in period, patients received twice daily (b.i.d.) axitinib 7 mg (n=3) or 10 mg (n=18) for 7 days followed by a 7-day dosing interruption; serial (18)FLT-PET scans were performed before day 1 and on days 7, 10, and 14. Axitinib plus FOLFIRI or FOLFOX was then administered in 2-week cycles; axitinib was interrupted on day 10 of each cycle for 7 days.
  
  
  RESULTS
  The maximum tolerated dose of axitinib was 10 mg b.i.d., in a week-on/week-off schedule, combined with FOLFIRI or FOLFOX. Common all-causality grade 3 adverse events were neutropenia (38%), hypertension (33%), and fatigue (29%). Of 21 patients, 2 (10%) had a partial response and 12 (57%) had stable disease. Following 7 days of continuous axitinib dosing, tumour (18)FLT uptake decreased -49% from baseline and recovered to -28% and -17% from baseline, respectively, after 3 and 7 days of axitinib interruption.
  
  
  CONCLUSIONS
  Axitinib administered in a week-on/week-off schedule combined with FOLFIRI or FOLFOX is supported by (18)FLT-PET data and was well tolerated in patients with gastrointestinal tumours.
authors.affiliation: Department of Radiology, University of California San Diego, San Diego, CA, USA.
authors.forename: C K
authors.initials: CK
authors.lastname: Hoh
authors.affiliation: Sarah Cannon Research Institute and Tennessee Oncology PLLC, Nashville, TN, USA.
authors.forename: H A
authors.initials: HA
authors.lastname: Burris
authors.affiliation: Sarah Cannon Research Institute and Tennessee Oncology PLLC, Nashville, TN, USA.
authors.forename: J C
authors.initials: JC
authors.lastname: Bendell
authors.affiliation: Pfizer Oncology, San Diego, CA, USA.
authors.forename: J
authors.initials: J
authors.lastname: Tarazi
authors.affiliation: Pfizer Oncology, San Diego, CA, USA.
authors.forename: B
authors.initials: B
authors.lastname: Rosbrook
authors.affiliation: Pfizer Oncology, San Diego, CA, USA.
authors.forename: S
authors.initials: S
authors.lastname: Kim
authors.affiliation: Sarah Cannon Research Institute and Tennessee Oncology PLLC, Nashville, TN, USA.
authors.forename: J R
authors.initials: JR
authors.lastname: Infante
authors.affiliation: Department of Medicine, University of California San Diego Moores Cancer Center, La Jolla, CA, USA.
authors.forename: T R
authors.initials: TR
authors.lastname: Reid
mesh_terms: D000328:Adult; D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D000077784:Axitinib; D000068258:Bevacizumab; D002166:Camptothecin / Q000031:analogs & derivatives / Q000627:therapeutic use; D005260:Female; D019788:Fluorodeoxyglucose F18; D005472:Fluorouracil / Q000627:therapeutic use; D005770:Gastrointestinal Neoplasms / Q000000981:diagnostic imaging* / Q000188:drug therapy*; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage* / Q000009:adverse effects; D007191:Indazoles / Q000008:administration & dosage* / Q000009:adverse effects; D002955:Leucovorin / Q000627:therapeutic use; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009944:Organoplatinum Compounds / Q000627:therapeutic use; D049268:Positron-Emission Tomography; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D019275:Radiopharmaceuticals; D028761:Withholding Treatment
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D007093:Imidazoles; D007191:Indazoles; D009944:Organoplatinum Compounds; D047428:Protein Kinase Inhibitors; D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18; D000068258:Bevacizumab; D000077784:Axitinib; D002955:Leucovorin; D005472:Fluorouracil; D002166:Camptothecin