Open-label phase I trial of vandetanib in combination with mFOLFOX6 in patients with advanced colorectal cancer.
BACKGROUND
Vandetanib (ZACTIMA) is a once-daily oral inhibitor of vascular endothelial growth factor, epidermal growth factor and RET receptor tyrosine kinases. The safety and tolerability of vandetanib plus mFOLFOX6 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 mFOLFOX6.


RESULTS
Seventeen patients received vandetanib 100 mg (n = 9) or 300 mg (n = 8) plus mFOLFOX6. The protocol definition of a tolerable dose (vandetanib-related dose-limiting toxicity [DLT] in less than two patients) was met in both dose cohorts, with one DLT of diarrhoea reported in each. Overall, the most common adverse events were diarrhoea, nausea and lethargy (all n = 11). There was no pharmacokinetic interaction between vandetanib and mFOLFOX6. Preliminary efficacy results included one complete response and three confirmed partial responses.


CONCLUSIONS
In patients with advanced CRC, once-daily vandetanib (100 or 300 mg) with mFOLFOX6 was generally well tolerated.
Michael
Michael
M
Division of Haematology and Medical Oncology, Peter MacCallum Cancer Centre, St Andrews Place, East Melbourne, Victoria, 3002, Australia. Michael.Michael@petermac.org
Gibbs
Peter
P
Smith
Robert
R
Godwood
Alex
A
Oliver
Stuart
S
Tebbutt
Niall
N
D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use*; D015331:Cohort Studies; D015179:Colorectal Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000473:pathology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005472:Fluorouracil / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009944:Organoplatinum Compounds / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use; D000077150:Oxaliplatin; D010880:Piperidines / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use*; D011799:Quinazolines / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use*; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; D010880:Piperidines; D011799:Quinazolines; D000077150:Oxaliplatin; D005472:Fluorouracil; C452423:vandetanib