A phase I, open-label study of the safety, tolerability and pharmacokinetics of lapatinib (GW572016) in combination with letrozole in cancer patients

3001 Background: Lapatinib is a selective and highly potent dual, competitive inhibitor of ErbB1 and ErbB2 tyrosine kinases leading to cell growth arrest and/or apoptosis in ErbB1 and ErbB2 dependent tumor cell lines and xenografts. Co-expression of ErbB2 and ER is associated with a reduced response rate to hormone therapy in breast cancer. A rational approach to treatment may be to block simultaneously both ER and ErbB2 pathways. Methods: Patients (pts) with advanced breast cancer, ER or PR +, or other tumors (e.g., ovarian, endometrial) that would be likely to respond to the combination therapy were enrolled. Escalating doses of lapatinib (1250–1500 mg/d) were administered in combination with letrozole (2.5 mg/d). Three pts were treated at each dose level, with expansion to 6 in the event of dose-limiting toxicity (DLT). Once the optimally tolerated regimen (OTR) was determined, an additional 8 - 16 pts were to be enrolled to establish the pharmacokinetic profiles of lapatinib and letrozole when adminis...