Abstract
We conducted a phase I study to assess safety, pharmacokinetics, pharmacodynamics, and activity of lonafarnib plus gemcitabine. Subjects received oral lonafarnib twice daily and gemcitabine on days 1, 8, and 15 every 28 days; multiple dose levels were explored. Lonafarnib had no apparent effect on gemcitabine PK. Mean lonafarnib half-life ranged from 4 to 7 hr; median T(max) values ranged from 4 to 8 hr. Two patients had partial response; seven patients had stable disease at least 6 months. Oral lonafarnib at 150 mg a.m./100 mg p.m. plus gemcitabine at 1,000 mg/m(2) is the maximum tolerated dose with acceptable safety and tolerability.
Publication types
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Clinical Trial, Phase I
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Multicenter Study
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Research Support, Non-U.S. Gov't
MeSH terms
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Administration, Oral
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Adult
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Aged
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Antineoplastic Combined Chemotherapy Protocols / administration & dosage*
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Antineoplastic Combined Chemotherapy Protocols / adverse effects
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Antineoplastic Combined Chemotherapy Protocols / pharmacokinetics
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Deoxycytidine / administration & dosage
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Deoxycytidine / adverse effects
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Deoxycytidine / analogs & derivatives
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Deoxycytidine / pharmacokinetics
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Dose-Response Relationship, Drug
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Female
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Gemcitabine
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Humans
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Infusions, Intravenous
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Male
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Middle Aged
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Neoplasms / drug therapy*
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Neoplasms / metabolism
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Piperidines / administration & dosage
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Piperidines / adverse effects
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Piperidines / pharmacokinetics
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Pyridines / administration & dosage
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Pyridines / adverse effects
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Pyridines / pharmacokinetics
Substances
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Piperidines
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Pyridines
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Deoxycytidine
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lonafarnib
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Gemcitabine