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A phase I study was designed to define the recommended dose of continuous intravenous 5-fluorouracil (5-FU) and the toxicity profile of this schedule when given as a 5-day continuous infusion. Twenty-six patients with advanced cancer were treated at seven dose levels ranging from 150 to 400 mg/m2/24 hours. A standard schedule of 24-hour continuous infusion of 5-FU was used in order to assess the pharmacokinetic profile of the drug. Non-hematologic toxicities were mild and reversible. The most common side effect was nausea and vomiting, occurring in 82% of patients. A dose of 300 mg/m2/24 hours was chosen as the recommended dose for clinical phase II trials based on favorable dose-intensity and toxicity profiles.In vivo modulation of nitric oxide during cerebral ischaemia: evidence for a pro-survival effect.
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