title: Vandetanib with FOLFIRI in patients with advanced colorectal adenocarcinoma: results from an open-label, multicentre Phase I study.
abstract: OBJECTIVE
  The safety and tolerability of vandetanib (ZACTIMA; ZD6474) plus FOLFIRI was investigated in patients with advanced colorectal cancer (CRC).
  
  
  METHODS
  Patients eligible for first- or second-line chemotherapy received once-daily oral doses of vandetanib (100 or 300 mg) plus 14-day treatment cycles of FOLFIRI.
  
  
  RESULTS
  A total of 21 patients received vandetanib 100 mg (n = 11) or 300 mg (n = 10) + FOLFIRI. Combination therapy was well tolerated at both vandetanib dose levels. There were no DLTs in the vandetanib 100 mg cohort and one DLT of hypertension (CTCAE grade 3) in the 300 mg cohort. The most common adverse events were diarrhoea (n = 20), nausea (n = 12) and fatigue (n = 10). Two patients (one in each cohort) discontinued vandetanib due to adverse events (rash, 100 mg cohort; hypertension, 300 mg cohort). There was no apparent pharmacokinetic interaction between vandetanib and FOLFIRI. Preliminary efficacy results included two confirmed partial responses in the 100 mg cohort and 9 patients with stable disease > or =8 weeks (100 mg, n = 7; 300 mg, n = 2).
  
  
  CONCLUSIONS
  Once-daily vandetanib (100 or 300 mg) in combination with a standard FOLFIRI regimen was generally well tolerated in patients with advanced CRC.
authors.affiliation: Christie Hospital, Manchester, UK. Mark.Saunders@christie.nhs.uk
authors.forename: Mark P
authors.initials: MP
authors.lastname: Saunders
authors.forename: Richard
authors.initials: R
authors.lastname: Wilson
authors.forename: Marc
authors.initials: M
authors.lastname: Peeters
authors.forename: Robert
authors.initials: R
authors.lastname: Smith
authors.forename: Alex
authors.initials: A
authors.lastname: Godwood
authors.forename: Stuart
authors.initials: S
authors.lastname: Oliver
authors.forename: Eric
authors.initials: E
authors.lastname: Van Cutsem
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy*; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use; D015179:Colorectal Neoplasms / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010880:Piperidines / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D011799:Quinazolines / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*
chemical_list: D010880:Piperidines; D011799:Quinazolines; C452423:vandetanib