A phase 1 study of intermittently administered pazopanib in combination with continuous daily dosing of lapatinib in patients with solid tumors

摘要: Purpose Preclinically, pazopanib/lapatinib combination acted synergistically to suppress the activity of multiple tyrosine kinases, including VEGFR-1, 2, 3, PDGFR and c-kit (pazopanib), HER1/EGFR HER2 (lapatinib), several other kinases c-Met through, plausibly, network inhibition effects. Clinically, continuous dosing was associated with a higher response rate than lapatinib monotherapy, poor tolerance. We explored intermittent dose levels pazopanib combined daily in patients solid tumors. Methods The present study used phase 1, modified 3 + dose-escalation design evaluate safety tolerability orally received once every day for 28 days. In expansion phase, tumor evaluated specific genetic alterations (HER2 amplification, mutation, EGFR mutation). Results Twenty-four were treated. most common drug-related adverse events fatigue 7/24 (29 %), skin rash 5/21 (21 diarrhea 3/24 (17 4/24 (16 %) experiencing grade ≥3 events. Escalation FDA-approved (800 mg 1500 lapatinib)