A drug interaction study of sorafenib (S) and rapamycin (R) in patients with advanced malignancies

2545 Background: R inhibits the mammalian target of rapamycin (mTOR) and is active in preclinical tumor models. S inhibits multiple kinases. S and mTOR inhibitors have activity in similar tumor types and may be synergistic. Methods: Design: A drug-drug interaction study of oral S and R in patients with PS 0–2 and histologically confirmed solid tumors with progressive disease after standard therapy or for which no standard therapy exists. Patients were assigned to one of two treatment arms in sequence. Arm A: S 400 mg bid starting day (D) 1, then S + R 3 mg qd starting D15. Arm B: R 3 mg qd starting D1, then R + S 400 mg bid starting D15. Primary endpoint: determine whether a significant pharmacokinetic interaction exists between R and S. Samples for pharmacokinetic analysis were collected on D1, 14, 15 and 29 (A) or D1, 8, 15, 22 (B). Paired t tests were used to compare mean drug concentrations. Results: 20 patients were enrolled from 4/07–10/07. Median age 54 (range 36–74); 55% men; PS 0: 60%, 1: 40%. 58...