Phase I dose-escalation study of 5-day intermittent oral lapatinib therapy in patients with human epidermal growth factor receptor 2-overexpressing breast cancer.

ABSTRACT:

Purpose

The highly effective treatment of human epidermal growth factor receptor (HER) 2-amplified breast cancer has proven challenging because of a signal buffering capacity inherent in the functionally relevant HER2-HER3 target. HER2-HER3 signaling can be inactivated by doses of lapatinib that fully inactivate the HER2 kinase. In mouse models, such doses are not tolerable in continuous administration, but they are tolerable and highly effective in intermittent dosing. We pursued the clinical translation of this treatment hypothesis.

Patients and methods

We conducted a phase I dose-escalation study in women with advanced HER2-overexpressing breast cancer. Lapatinib was administered on days 1 through 5 of repeating 14-day cycles. Dose escalation was conducted using a 3+3 des

SUBMITTER: Chien AJ 

PROVIDER: S-EPMC4017711 | biostudies-literature | 2014 May

REPOSITORIES: biostudies-literature