Vandetanib with FOLFIRI in patients with advanced colorectal adenocarcinoma: results from an open-label, multicentre Phase I study.
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.
Saunders
Mark P
MP
Christie Hospital, Manchester, UK. Mark.Saunders@christie.nhs.uk
Wilson
Richard
R
Peeters
Marc
M
Smith
Robert
R
Godwood
Alex
A
Oliver
Stuart
S
Van Cutsem
Eric
E
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*
D010880:Piperidines; D011799:Quinazolines; C452423:vandetanib