Phase I dosage-finding and pharmacokinetic (PK) study of intravenous topotecan and oral erlotinib in patients (pts) with refractory solid tumors

2549 Background: Topotecan (TPT) is a substrate for efflux transporters of the ABC family. Erlotnib (E), a 4-aniloquinazole, inhibits ABCG2 at clinically achievable plasma concentrations. This phase I study was designed to determine the maximum tolerated dose (MTD) of this combination of two active anticancer drugs with ABC transporter modulation capability and assess PK interactions. Methods: Escalating dose levels (DL) of 3 pt cohorts each of TPT IV at 0.75 mg/m2 (DL 1); 1.0 mg/m2 (DL 2); and 1.25 mg/m2 (DL 3); day 1 -5 q 21 day cycle. E was added on cycle 1, day 2 at 150 mg po daily continuously. Serial plasma samples were obtained pre and post TPT day 1, cycle 1 and day 1, cycle 2 or 3 and 24 hr urine samples were obtained after cycle 1 and cycle 2. Dose-limiting toxicity (DLT) was defined as G4 hematologic and/or G3/4 nonhematologic toxicities. Results: 23 enrolled pts included 4 ovarian, 4 colorectal, 4 sarcoma, 4 small cell lung, and 7 other tumors; 16 were Caucasian and 7 African American. Median ...