title: Phase I study of perillyl alcohol in patients with refractory malignancies.
abstract: We treated 21 patients in a dose-finding and pharmacokinetic study of the monoterpene perillyl alcohol with the drug given orally in 3 divided doses on a chronic basis. The average number of days that patients remained on study was 48 (range 11-172). Fatigue and low-grade nausea were dose limiting. Using this schedule, a starting dose of 1.6 g/m2 with escalation to 2.1 g/m2 as tolerated is recommended. Two major metabolites were detectable and the mean peak plasma concentrations were 383 microM for perillic acid and 27 microM for dihydroperillic acid. The peak plasma concentration and the metabolite half-life were 2 h and 1 h post ingestion for perillic acid, and 4 h and 2.4 h for dihydroperillic acid, respectively. Stabilization of disease was observed in one of the 16 patients evaluable for response. Many of the gastrointestinal side effects that were poorly tolerated on a chronic basis may be partly related to the soybean oil base used in the current formulation. Further development of perillyl alcohol on this schedule would be facilitated by reformulation of the capsule.
authors.affiliation: Departments of Medicine, Pharmacology, Obstetrics and Gynecology, Cancer Center, Yale University School of Medicine, 333 Cedar St., NSB 287, New Haven, Connecticut 06520, USA. John.Murren@yale.edu
authors.forename: John R
authors.initials: JR
authors.lastname: Murren
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Pizzorno
authors.forename: Susan A
authors.initials: SA
authors.lastname: DiStasio
authors.forename: Anne
authors.initials: A
authors.lastname: McKeon
authors.forename: Kathleen
authors.initials: K
authors.lastname: Peccerillo
authors.forename: Ashwin
authors.initials: A
authors.lastname: Gollerkari
authors.forename: Walter
authors.initials: W
authors.lastname: McMurray
authors.forename: Barbara A
authors.initials: BA
authors.lastname: Burtness
authors.forename: Thomas
authors.initials: T
authors.lastname: Rutherford
authors.forename: Xin
authors.initials: X
authors.lastname: Li
authors.forename: Peter T C
authors.initials: PT
authors.lastname: Ho
authors.forename: Alan
authors.initials: A
authors.lastname: Sartorelli
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D039821:Monoterpenes; D009369:Neoplasms / Q000188:drug therapy*; D013729:Terpenes / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*
chemical_list: D000970:Antineoplastic Agents; D039821:Monoterpenes; D013729:Terpenes; C032208:perillyl alcohol