The phase I study assessed dose-limiting toxicities, maximum tolerated dose, and pharmacokinetics of AN-152 given once every three weeks in patients with gynaecological and breast cancers.
Eight patients entered the study and received AN-152 by intravenous infusion over two hours at dosages of 10, 20, 40, 80, 160, and 267mg/m(2). Observation of a grade 2 leukocytopenia in a patient at 160mg/m(2) led to the addition of three other patients at this dose level.
Patients received at least two treatment courses, 21 days apart, and went off study with progressive disease. However, one of the three patients at the dose level of 160mg/m(2) with a diagnosis of ovarian cancer showed stabilization of disease and received four treatment courses.
Infusion of AN-152 was well tolerated at all dosages, without supportive treatment. Pharmacokinetic analyses showed dose-dependent plasma levels of AN-152 and only minor (10% to 20%) release of doxorubicin.
From these data, AEterna Zentaris has concluded that infusion of AN-152 is well tolerated in female patients. No dose-limiting toxicities were seen up to 267mg/m(2), which is equimolar to a doxorubicin dose of 77mg/m(2). Recruitment at this dose level is ongoing.
The results formed part of an abstract published at the 42nd annual meeting of the American Society of Clinical Oncology (ASCO).