Publications by authors named "L A Cartee"
Introduction This Phase Ib trial investigated the safety, tolerability, and recommended phase 2 dose for the pan-PI3K/mTOR inhibitor, GSK2126458 (GSK458), and trametinib combination when administered to patients with advanced solid tumors. Patients and Methods Patients with advanced solid tumors received escalating doses of GSK458 (once or twice daily, and continuous or intermittent) and trametinib following a zone-based 3 + 3 design to determine the maximum tolerated dose (MTD). Assessments included monitoring for adverse events and response, and evaluating pharmacokinetic (PK) measures.
View Article and Find Full Text PDFThe potential for an interaction between lapatinib and absorption of the P-glycoprotein (ABCB1) substrate digoxin at a therapeutic dose in breast cancer patients was characterized. Seventeen women with HER2-positive metastatic breast cancer received a single oral 0.5-mg dose of digoxin on days 1 and 9 and oral lapatinib 1500 mg once daily on days 2 through 9.
View Article and Find Full Text PDFPurpose: The paradigm shift in cancer treatment from cytotoxic drugs to tumor targeted therapies poses new challenges, including optimization of dose and schedule based on a biologically effective dose, rather than the historical maximum tolerated dose. Optimal dosing is currently determined using concentrations of tyrosine kinase inhibitors in plasma as a surrogate for tumor concentrations. To examine this plasma-tumor relationship, we explored the association between lapatinib levels in tumor and plasma in mice and humans, and those effects on phosphorylation of human epidermal growth factor receptors (HER) in human tumors.
View Article and Find Full Text PDFArticle Synopsis
- Lapatinib is used to treat metastatic breast cancers that over-express HER2, but current tablets require taking up to six large pills, prompting the development of a powder for oral suspension.
- A study was conducted to compare the powder and the tablets in advanced cancer patients using a two-period crossover design, which allows for a more efficient trial with fewer subjects needed.
- The study showed that the powder was bioequivalent to the tablets, fulfilling the criteria for absorption rates and safety, meaning patients can safely switch to the easier-to-take powder formulation.
Aim: To quantify the effect of food on the systemic exposure of lapatinib at steady state when administered 1 h before and after meals, and to observe the safety and tolerability of lapatinib under these conditions in patients with advanced solid tumours.
Methods: This was a three-treatment, randomised, three-sequence cross-over study. Lapatinib was administered 1 h after a low- [B] or a high-fat [C] meal and systemic exposure was compared with that obtained following administration 1 h before a low-fat meal [A].