Phase I Study of Perillyl Alcohol in Patients with Refractory Malignancies
Volume 1, Issue 2
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Pages 130 - 135
Authors: John R. Murren, Giuseppe Pizzorno, Susan A. DiStasio, Anne McKeon, Kathleen Peccerillo, Ashwin Gollerkari, Walter McMurray, Barbara A. Burtness, Thomas Rutherford, Xin Li, Peter T. C. Ho and Alan Sartorelli View affiliations
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 µM for perillic acid and 27 µM for dihydroperillic acid. The peak plasma
concentration and the metabolite half-life were 2h and 1h 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.