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).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.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.In patients with advanced CRC, once-daily vandetanib (100 or 300 mg) with mFOLFOX6 was generally well tolerated.