Phase I dose escalation study of MK-0457, a novel Aurora kinase inhibitor, in adult patients with advanced solid tumors.

RESULTS: Twenty-seven patients received a total of 86 infusions of MK-0457. Dose-limiting toxicity at 96 mg/m(2)/h included grade 4 neutropenia and grade 3 herpes zoster (shingles). The MTD was identified as 64 mg/m(2)/h. The most common adverse events were nausea, vomiting, diarrhea, and fatigue. Pharmacokinetic analyses revealed that CIV infusion MK-0457 had an estimated mean terminal half-life of approximately 6.6-10.2 h and that end-of-infusion concentrations and mean AUCs were approximately dose proportional. The estimated mean oral bioavailability of MK-0457 was 7.9%.
One patient with advanced ovarian cancer attained prolonged stable disease for 11 months.  
CONCLUSIONS: MK-0457 was well tolerated in this schedule. Almost half the patients attained stable disease. Further development of this class of agents will likely occur in combination with other anti-cancer treatments.