Function of the Aurora kinase inhibitor, Tozasertib, in adult patients with advanced solid tumors

Traynor AM, Hewitt M, Liu G, Flaherty KT, Clark J, Freedman SJ, Scott BB, Leighton AM, Watson PA, Zhao BT, O'Dwyer PJ, Wilding G "CANCER CHEMOTHERAPY AND PHARMACOLOGY FEB 2011"

To assess the maximum-tolerated dose (MTD), dose-limiting toxicity (DLT), safety, and tolerability with the 24-h ongoing intravenous (CIV) infusion of Tozasertib, a novel pan-Aurora kinase inhibitor, in individuals with superior sound tumors and also to establish the bioavailability of an oral dose of 100 mg Tozasertib.

Tozasertib was administered as being a 24-h CIV infusion every 21 days. Dose escalation proceeded per toxicity criteria. A 100-mg oral dose was administered to seven individuals forty eight h prior towards the CIV infusion dose of 64 mg/m(2)/h.

Twenty-seven individuals obtained a somme of 86 infusions of MK-0457. Dose-limiting toxicity at 96 mg/m(2)/h incorporated grade 4 neutropenia and grade three herpes zoster. The MTD was determined as 64 mg/m(2)/h. Essentially the most typical adverse events had been nausea, vomiting, diarrhea, and tiredness.

Pharmacokinetic analyses exposed that CIV infusion Tozasertib had an believed imply terminal half-life of roughly six.6-10.2 h and that end-of-infusion concentrations and mean AUCs had been approximately dose proportional. The approximated indicate oral bioavailability of MK-0457 was seven.9%. One affected individual with advanced ovarian cancer attained extended stable illness for 11 months.

MK-0457 was nicely tolerated in this schedule. Nearly 50 % the patients attained stable disease. Additional development of this class of agents will likely occur in combination with other anti-cancer remedies.