Phase I clinical evaluation of AZD2171, a highly potent VEGF receptor tyrosine kinase inhibitor, in patients with advanced tumors

3002 Background: AZD2171 is a highly potent and orally available inhibitor of VEGF receptor tyrosine kinase activity, and has shown antitumor activity in a wide range of tumor xenograft models. This Phase I trial was designed to assess the safety, tolerability and pharmacokinetics (PK) of ascending doses of AZD2171 in patients with advanced tumors with liver metastases. Methods: Eligibility criteria included solid tumors refractory to standard therapies and a WHO performance status of 0–2. Patients received a single oral dose of AZD2171 (0.5–60 mg) followed by a 7-day washout period, before continuing daily oral therapy at the same initial dose for 28 days. Further 28-day cycles were administered until a withdrawal criterion was met. Results: As of Sep 10, 2004, 36 patients (19–75 years) have received treatment with AZD2171 (0.5, 1, 2.5, 5, 10, 20, 30, 45 or 60 mg; n = 3, 3, 3, 3, 4, 3, 5, 4 and 8, respectively). AZD2171 was generally well tolerated at doses ≤45 mg/day. Overall, the most common adverse ev...