Phase I study of an oral formulation of irinotecan administered daily for 14 days every 3 weeks in patients with advanced solid tumours.

A phase I study was conducted with oral irinotecan given daily for 14 days every 3 weeks in 45 patients with solid tumours to establish the maximum tolerated dose (MTD), toxicity, preliminary antitumour response and pharmacokinetics. Irinotecan was administered orally as a powder-filled capsule at doses ranging from 7.5 to 40 mg/m2 per day.

Randomized phase I clinical and pharmacologic study of weekly versus twice-weekly dose-intensive cisplatin and gemcitabine in patients with advanced non-small cell lung cancer.

Purpose: To establish the maximum dose intensity of cisplatin plus gemcitabine on a weekly or two-weekly schedule in patients with advanced non-small cell lung cancer (NSCLC).

Methods: Patients with NSCLC stage IIIB or IV were randomized to receive weekly or two-weekly courses of gemcitabine on day 1 and cisplatin on day 2. An interpatient dose escalation scheme was used, and pharmacokinetics were determined for both agents in plasma and WBCs.

High-performance liquid chromatographic analysis of the anticancer drug irinotecan (CPT-11) and its active metabolite SN-38 in human plasma.

A rapid, sensitive, and specific high-performance liquid chromatography (HPLC) method for the simultaneous determination of irinotecan (CPT-11) and its active metabolite SN-38 in human plasma is described. The analytes are quantified as the totals of their carboxylate and lactone form. The sample pretreatment consisted of a simple protein precipitation with acetonitrile-methanol (1:1, v/v), after which CPT-11 and SN-38 were quantitatively converted to their carboxylate form by adding 0.

Development of an optimal pharmacokinetic sampling schedule for rubitecan administered orally in a daily times five schedule.

Purpose: Our aim was to develop an optimal sampling strategy for the description of the pharmacokinetics of rubitecan and its active metabolite 9-aminocamptothecin (9-AC) for use in phase II/III studies with oral rubitecan administered in a daily times five schedule.

Methods: Concentration-time data of rubitecan and 9-AC were obtained from 14 patients who had received 1.5 mg/m(2) per day rubitecan orally.

Determination of 9-nitrocamptothecin and its metabolite 9-aminocamptothecin in human plasma using high-performance liquid chromatography with ultraviolet and fluorescence detection.

A high-performance liquid chromatography assay is described for the determination of the investigational anti-cancer drug 9-nitrocamptothecin (9-NC) and its metabolite 9-aminocamptothecin (9-AC) as the total of their lactone and carboxylate forms. The sample pre-treatment consisted of a deproteinisation step and a quantitative acid-catalyzed conversion of all 9-NC and 9-AC into their lactone forms and a subsequent solid-phase extraction. Redissolved extracts were analyzed on a Prodigy analytical column, using a mixture of methanol-phosphate buffer (pH 2.

Urinary and fecal excretion of topotecan in patients with malignant solid tumours.

Purpose: The objectives of the study were to determine the pharmacokinetics and routes of excretion of topotecan following intravenous or oral administration to patients with refractory solid tumours.

Methods: Patients were randomized to receive either oral (2.3 mg/m(2)) or intravenous (1.

Topoisomerase I levels in white blood cells of patients with ovarian cancer treated with paclitaxel-cisplatin-topotecan in a phase I study.

Topotecan stabilizes the topoisomerase I (Topo I) cleavable complex. We measured Topo I levels in white blood cells of patients with ovarian cancer treated with topotecan. Topotecan was given i.