Safety, Pharmacokinetics, and Efficacy of CPX-1 Liposome Injection in Patients with Advanced Solid Tumors

摘要: Purpose: CPX-1 is a novel, liposome-encapsulated formulation of irinotecan and floxuridine designed to prolong in vitro optimized synergistic molar ratios both drugs postinfusion. This open-label, single-arm, dose-escalating phase I study was determine the maximum tolerated dose pharmacokinetics patients with advanced solid tumors. Experimental Design: Patients received at 30, 60, 100, 150, 210, or 270 units/m 2 (1 unit = 1 mg + 0.36 floxuridine) infused over 90 minutes every 14 days 28-day cycles. Pharmacokinetic samples were collected on 15 cycle 1. Results: Thirty-three enrolled, treated, evaluated for safety; 30 response. A 1:1 plasma ratio maintained 8 12 hours. Grade 3/4 toxicities included diarrhea (24.2%), neutropenia (12.1%), hypokalemia (12.1%); patient (270 ) died persistent diarrhea, which led dehydration renal failure (grade 5). Partial response occurred 3 (12%) 25 subjects through Response Evaluation Criteria Solid Tumors. Progression-free survival lasting >6 months 9 patients, 6 colorectal cancer. Among cancer (10 prior irinotecan), calculated median progression-free 5.4 months; 11 (72.7%) achieved disease control (13%) had partial Conclusions: Outpatient well antitumor activity shown The recommended future studies 210 . first clinical evaluation fixed drug dosing maintain enhanced therapeutic benefit.