Cancer chemotherapy and pharmacology
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Cancer Chemother. Pharmacol. · Jan 1999
Interpatient variability in bioavailability of the intravenous formulation of topotecan given orally to children with recurrent solid tumors.
Evaluation of inter- and intrapatient variability of topotecan oral bioavailability and disposition was performed in children with malignant solid tumors. ⋯ Large interpatient variability was noted in topotecan pharmacokinetics, whereas intrapatient variability was relatively small. Further studies of oral topotecan are warranted to evaluate the tolerance of shorter courses and to define further the interpatient variability.
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Cancer Chemother. Pharmacol. · Jan 1999
Favorable therapeutic index of a p210(BCR-ABL)-specific tyrosine kinase inhibitor; activity on lineage-committed and primitive chronic myelogenous leukemia progenitors.
In order to assess the effect of the tyrosine kinase inhibitor CGP57148B on lineage-committed and primitive chronic myelogenous leukemia (CML) progenitor cells, peripheral blood progenitor cells (PBPC) mobilized in chronic phase CML were exposed to this compound in vitro. ⋯ The results support the use of CGP57148B either for short-term exposure in vitro (e.g. purging) or for continuous treatment of CML in vivo.
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Cancer Chemother. Pharmacol. · Jan 1998
Multicenter Study Clinical TrialA clinical pharmacokinetics study of carzelesin given by short-term intravenous infusion in a phase I study.
We investigated the pharmacokinetic behavior of carzelesin in 31 patients receiving this drug by 10-min intravenous infusion in a Phase I clinical trial, which was conducted at institutions in Nijmegen (institution 1) and Brussels (institution 2). The dose steps were 24, 48, 96, 130, 150, 170, 210, 250, and 300 microg/m2. Carzelesin is a cyclopropylpyrroloindole prodrug that requires metabolic activation via U-76,073 to U-76,074. ⋯ The results recorded for patients in institution 1 indicated that the AUC increased proportionately with increasing doses. There was a good correlation between the maximal plasma concentration and the AUC, enabling future monitoring of drug exposure from one timed blood sample. Urinary excretion of carzelesin was below 1% of the delivered dose.
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Cancer Chemother. Pharmacol. · Jan 1998
Effects of demographic variables on vorozole pharmacokinetics in healthy volunteers and in breast cancer patients.
Vorozole (VOR) is a selective nonsteroidal inhibitor of the cytochrome P450-dependent aromatase that catalyzes the conversion of androgens to estrogens. It is currently being developed as a therapeutic agent in the endocrine treatment of postmenopausal women with breast cancer. This work was aimed to explore the effects of demographic and other variables on VOR pharmacokinetics. ⋯ Healthy volunteer/patient, single/multiple dosing differences, and age were identified as the fixed effects influencing the CL of VOR. WT was the main determinant of distributional PK parameters. The peripheral and steady-state volumes of distribution were gender-dependent. In view of the relatively high degree of residual interpatient variability in CL, the slight effect of age on it is unlikely to be clinically significant.
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Cancer Chemother. Pharmacol. · Jan 1998
Practical implementation of a modified continual reassessment method for dose-finding trials.
We describe a practical, reliable, efficient dose-finding design for cytotoxic drugs applied in a multi-institutional setting. ⋯ Our experience demonstrates the feasibility of implementing this design in multi-institutional trials and the possibility of performing dose-finding studies that require fewer patients than conventional methods.