British journal of cancer
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British journal of cancer · Nov 1998
Clinical TrialA phase I clinical and pharmacokinetic study of the new topoisomerase inhibitor GI147211 given as a 72-h continuous infusion.
GI147211 is a novel, totally synthetic camptothecin with promising preclinical and early clinical activity. This study was designed to determine the maximum tolerated dose of Gl147211 as a 72-h infusion and to describe its pharmacokinetics and pharmacodynamics on this schedule. In a single-arm, rising-dose study in patients with advanced cancer, eight cohorts of three or more patients received 72-h infusions of Gl147211 at doses ranging from 0.25 to 2.5 mg m(-2) day(-1). ⋯ The recommended phase II doses for this regimen are 1.75 mg m(-2) day(-1) and 1.2 mg m(-2) day(-1) for minimally pretreated and heavily pretreated patients respectively. At these doses, steady-state Gl147211 concentrations within the range of those effective in vitro were achieved. Extensive phase II evaluation of this compound and further phase I trials evaluating more prolonged infusions are ongoing.