BACKGROUND: We wished to define the maximum tolerated dose (MTD), toxicity, and pharmacokinetics of the novel isoflav-3-ene, NV06 (Phenoxodioltrade mark), a compound with a diphenolic structure related chemically and biologically to genistein and flavopiridol. PATIENTS AND METHODS: Twenty-one patients with advanced cancers were treated with weekly intravenous administration of NV06 at escalating dose levels with 1-4 patients at each dose cohort. Plasma sampling was undertaken to characterize the pharmacokinetic (PK) profile of the compound. RESULTS: Toxicity was minimal, with asymptomatic Grade 3 lymphocytopenia occurring in nine patients. Nine patients developed Grade 1 nausea, six patients developed Grade 1 increases in alkaline phosphatase, and six patients developed Grade 1 increases in transaminases. Two patients experienced hypersensitivity reactions. The MTD was not reached. Most patients had progressive disease on treatment but eight completed 12 weeks and two completed 24 weeks of treatment. The best response was stable disease of 6 months duration. The plasma half-life (T1/2), clearance (Cl), and volume of distribution (VD) were 304 (+/-91) min, 82 (+/-19) ml/min and 32,663 (+/-7,199) ml, respectively, for total NV06. CONCLUSIONS: NV06 is well tolerated and can be given safely as an intravenous infusion over 1-2 h at a dose of at least 30 mg/kg.
BACKGROUND: We wished to define the maximum tolerated dose (MTD), toxicity, and pharmacokinetics of the novel isoflav-3-ene, NV06 (Phenoxodioltrade mark), a compound with a diphenolic structure related chemically and biologically to genistein and flavopiridol. PATIENTS AND METHODS: Twenty-one patients with advanced cancers were treated with weekly intravenous administration of NV06 at escalating dose levels with 1-4 patients at each dose cohort. Plasma sampling was undertaken to characterize the pharmacokinetic (PK) profile of the compound. RESULTS:Toxicity was minimal, with asymptomatic Grade 3 lymphocytopenia occurring in nine patients. Nine patients developed Grade 1 nausea, six patients developed Grade 1 increases in alkaline phosphatase, and six patients developed Grade 1 increases in transaminases. Two patients experienced hypersensitivity reactions. The MTD was not reached. Most patients had progressive disease on treatment but eight completed 12 weeks and two completed 24 weeks of treatment. The best response was stable disease of 6 months duration. The plasma half-life (T1/2), clearance (Cl), and volume of distribution (VD) were 304 (+/-91) min, 82 (+/-19) ml/min and 32,663 (+/-7,199) ml, respectively, for total NV06. CONCLUSIONS:NV06 is well tolerated and can be given safely as an intravenous infusion over 1-2 h at a dose of at least 30 mg/kg.
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