Pharmacokinetics of dexrazoxane in subjects with impaired kidney function.

Dexrazoxane is approved as a cardioprotective agent for use in female patients with breast cancer who are receiving doxorubicin. The effect of renal insufficiency on elimination is not known. The pharmacokinetics of dexrazoxane 150 mg/m(2), given as a 15-minute constant-rate intravenous infusion, were assessed in 24 men and women with varying degrees of renal function in a single-dose, open-label, parallel-group study.

A phase I study of the safety and pharmacokinetics of edotecarin (J-107088), a novel topoisomerase I inhibitor, in patients with advanced solid tumors.

Purpose: To assess the maximum tolerated dose, safety, and pharmacokinetic (PK) profile of escalating doses of the novel topoisomerase I (topo I) inhibitor edotecarin (J-107088) given as a 2-h intravenous (IV) infusion once every 21 days in patients with advanced solid tumors who had not responded to standard therapy.

Patients And Methods: Twenty-nine patients (18M:11F) received a 2-h IV infusion of edotecarin in doses of 6, 8, 11, 13, or 15 mg/m(2) every 21 days (with an additional 1-2 weeks permitted for recovery) and were evaluated for safety, PK, and tumor response.

Results: The most common non-hematologic toxicities were grade 1-2 nausea, fatigue, anorexia, vomiting, and fever.

Phase 1 and pharmacokinetic study of intravenous irinotecan in refractory solid tumor patients with hepatic dysfunction.

Purpose: To determine the recommended starting doses and pharmacokinetics of irinotecan in cancer patients with impaired liver function treated on a weekly schedule.

Experimental Design: Patients with solid tumors who had impaired liver function were enrolled into four groups based on baseline serum total bilirubin and aspartate aminotransferase (AST)/alanine aminotransferase (ALT): Group 1 (n = 19): total bilirubin 1.5 to 3.

Phase I and pharmacokinetic study of edotecarin, a novel topoisomerase I inhibitor, administered once every 3 weeks in patients with solid tumors.

Purpose: Edotecarin (J-107088) is a potent indolocarbazole topoisomerase I inhibitor which is structurally distinct from the camptothecins. This study aimed to determine the maximum tolerated dose (MTD), the recommended dose for future Phase II studies and the safety, pharmacokinetic profile, and preliminary antitumor activity of edotecarin in a population of patients with advanced solid tumors.

Experimental Design: Edotecarin was administered as a single dose by IV infusion over 2 h every 21 days (with 1 week permitted for recovery from toxicities, if needed) in patients with advanced solid tumors.

Relationship of baseline serum bilirubin to efficacy and toxicity of single-agent irinotecan in patients with metastatic colorectal cancer.

Purpose: To examine the predictive value of baseline serum bilirubin measurement for chemotherapy-related toxicity or efficacy among patients receiving irinotecan for metastatic colorectal cancer.

Methods: We performed a secondary analysis of a cohort of 287 patients treated in a multicenter, phase III study with single-agent irinotecan administered either weekly or once every 3 weeks. Patients were grouped into three categories of baseline bilirubin measurements (0 to 0.