AZD2171 (RECENTIN™) shows promising anti-tumour activity in advanced solid tumours

Researchers have reported that AZD2171 (RECENTIN™; AstraZeneca) shows promising anti-tumour activity and is generally well-tolerated in various advanced solid tumours, in a study reported in the Journal of Clinical Oncology this week.

AZD2171 is a highly potent oral selective inhibitor of vascular endothelial growth factor (VEGF) signaling, thereby inhibiting tumour angiogenesis.

This Phase I study consisted of two parts. In part A, 36 patients with advanced solid tumours and liver metastases received al AZD2171 0.5 to 60 mg, once daily to identify the maximum tolerated dose. In part B, 36 patients with and 11 patients without liver metastases received oral AZD2171 (20, 30 or 45 mg). Patients continued to receive treatment until tumour progression or dose-limiting toxicity occurred.

Eighty-three patients received AZD2171, which was generally well-tolerated up to a dose of 45 mg/day. Most frequently reported adverse events included diarrhea, dysphonia and hypertension, and the most common dose-limiting toxicity was hypertension in 7/83 (8.4%) patients at doses ≥ 20 mg.

Maximum peak drug concentrations after a single dose of AZD2171 occurred between 1 and 8 hours post-AZD2171 administration with a mean half-life of 22 hours.

Promising anti-tumour activity was observed with two (2.4%) patients achieving confirmed partial responses and 22 (26.5) patients achieving stable disease.

Author’s conclusions: Once-daily oral AZD2171 at doses of ≤45 mg was generally well tolerated and associated with encouraging anti-tumour activity in patients with a broad range of advanced solid tumours.

Additional information: a number of clinical trials of AZD2171 as a single-agent or in combination with other agents in various solid tumours are ongoing (follow link below)

http://www.astrazenecaclinicaltrials.com/article/516060.aspx

Source: http://jco.ascopubs.org/cgi/content/abstract/25/21/3045