Clinical evaluation of AZD1152, an i.v. inhibitor of Aurora B kinase, in patients with solid malignant tumors.

D.S. Boss, P.O. Witteveen, J. van der Sar, M.P.J.K. Lolkema, E.E. Voest, P.K. Stockman, O. Ataman, D. Wilson, S. Das, J.H.M. Schellens

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BACKGROUND: To determine, for each of two dosing schedules, the dose-limiting toxicity (DLT) and maximum-tolerated dose (MTD) of AZD1152, an Aurora B kinase inhibitor, and to evaluate its safety, biologic activity and pharmacokinetics (PK). PATIENTS AND METHODS: Patients with advanced solid malignancies were treated with escalating doses (100-650 mg) of AZD1152, administered as a 2-h infusion every 7 days (A) or 14 days (B). Adverse events (AEs), PK variables and tumor response were assessed. RESULTS: Fifty-nine patients were treated; 19 in schedule A and 40 in schedule B. The MTDs were 200 and 450 mg, respectively. Neutropenia (with/without fever) was the most frequent AE and DLT in each schedule. Common Terminology Criteria of Adverse Events version 3.0 grade >/=3 neutropenia and leukopenia occurred in 58% and 11% of patients, respectively, in schedule A and 43% and 20%, respectively, in schedule B. No objective tumor responses were observed at any dose or schedule, although stable disease, as defined by RECIST, was achieved in 15 patients (25%) overall. Systemic exposure to AZD1152-hQPA (active drug) was observed by 1 h into the infusion and exhibited linear PK. CONCLUSIONS: AZD1152 was generally well tolerated with neutropenia being the most frequently reported AE and DLT. Exposure to AZD1152-hQPA, the active drug of AZD1152, was linear.
Original languageUndefined/Unknown
Pages (from-to)431-7
Number of pages7
JournalAnnals of Oncology
Issue number2
Publication statusPublished - 2011

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