Phase I pharmacokinetic, food effect, and pharmacogenetic study of oral irinotecan given as semisolid matrix capsules in patients with solid tumors.

Purpose: To characterize the maximum-tolerated dose, recommended dose, dose-limiting toxicities (DLT), pharmacokinetic profile, and food effect of orally administered irinotecan formulated as new semisolid matrix capsules.

Experimental Design: Irinotecan was given orally in fasted patients once daily for 5 consecutive days and repeated every 3 weeks. Patients were randomly assigned to take the drug along with a high-fat, high-calorie breakfast for the administration at day 1 of the first or second cycle.

Phase I and pharmacokinetic study of DE-310 in patients with advanced solid tumors.

Purpose: To assess the maximum-tolerated dose, toxicity, and pharmacokinetics of DE-310, a macromolecular prodrug of the topoisomerase I inhibitor exatecan (DX-8951f). in patients with advanced solid tumors.

Experimental Design: Patients received DE-310 as a 3-hour infusion once every 2 weeks (dose, 1.

Phase I and pharmacokinetic study of oral irinotecan given once daily for 5 days every 3 weeks in combination with capecitabine in patients with solid tumors.

Purpose: To assess the maximum tolerated dose, dose-limiting toxicity, pharmacokinetics, and preliminary antitumor activity of oral irinotecan given in combination with capecitabine to patients with advanced, refractory solid tumors.

Patients And Methods: Patients were treated from day 1 with irinotecan capsules given once daily for 5 consecutive days (50 to 60 mg/m2/d) concomitantly with capecitabine given twice daily for 14 consecutive days (800 to 1,000 mg/m2); cycles were repeated every 21 days.

Results: Twenty-eight patients were enrolled and received 155 cycles of therapy (median, five cycles; range, one to 18 cycles).

Liquid chromatographic assays for DE-310, a novel camptothecin analog, and two major enzymatic products in human matrices.

Assays were developed for determination of DE-310, a carboxymethyldextran polyalcohol conjugate of the topoisomerase I inhibitor DX-8951 (exatecan) and two enzymatic products (i.e. glycyl-DX-8951 and unconjugated DX-8951) in human whole blood, erythrocytes and saliva.