Phase II trial of perillyl alcohol (NSC 641066) administered daily in patients with metastatic androgen independent prostate cancer.
OBJECTIVE
We conducted a phase II multicenter trial of perillyl alcohol in patients with advanced hormone refractory prostate cancer (HRPC). The primary endpoint was to evaluate the 6-month progression-free survival given the potential cytostatic nature of the drug. Secondary objectives included assessing acute and chronic toxicities, as well as measuring objective response rates.


METHODS
Patients with metastatic androgen-independent prostate cancer that failed at least one prior chemotherapeutic or experimental regimen were eligible. Perillyl alcohol was administered orally at 1200 mg/m2/dose four times daily and continued until disease progression or development of unacceptable toxicity.


RESULTS
Fifteen patients were eligible. Six patients received less than one cycle (4 weeks) of drug, four of which stopped because of drug intolerance. Only six patients received more than two cycles of therapy and were considered evaluable for response. Main toxicity included grade 1-2 gastrointestinal intolerance (nausea/vomiting in 60% of the patients) and fatigue (47%). One patient developed a grade 4 hypokalemia that was felt likely attributable to the drug. No objective responses were seen. All patients either progressed or withdrew from the study secondary to drug intolerance before the 6-month time period.


CONCLUSIONS
Perillyl alcohol administered at this dose and formulation did not have any objective clinical activity in this patient population.
Liu
Glenn
G
University of Wisconsin Comprehensive Cancer Center, Madison, WI 53792, USA.
Oettel
Kurt
K
Bailey
Howard
H
Ummersen
Lynn Van
LV
Tutsch
Kendra
K
Staab
Mary Jane
MJ
Horvath
Dorothea
D
Alberti
Dona
D
Arzoomanian
Rhoda
R
Rezazadeh
Hamied
H
McGovern
James
J
Robinson
Emily
E
DeMets
David
D
Wilding
George
G
D000284:Administration, Oral; D000368:Aged; D000369:Aged, 80 and over; D000728:Androgens / Q000378:metabolism; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D004334:Drug Administration Schedule; D006801:Humans; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D039821:Monoterpenes / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D016212:Transforming Growth Factor beta / Q000097:blood; D053773:Transforming Growth Factor beta1; D016896:Treatment Outcome
D000728:Androgens; D000970:Antineoplastic Agents; D039821:Monoterpenes; C508960:TGFB1 protein, human; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; C032208:perillyl alcohol