Phase I dose escalation trial of feverfew with standardized doses of parthenolide in patients with cancer.
OBJECTIVE
Feverfew is a botanical product that contains parthenolide. Parthenolide has in vitro and in vivo anti-tumor and anti-angiogenic activity. Feverfew has been used extensively without any formal pharmacokinetic analysis. A Phase I trial was conducted to evaluate the pharmacokinetics and toxicity of parthenolide given as a component of "feverfew."


METHODS
Feverfew (Tanacet trade mark ) was administered as a daily oral tablet in a 28-day cycle. A starting dose of 1 mg per day was explored with subsequent dose escalations to 2, 3, and 4 mg. Assessment of plasma pharmacokinetics was performed on patients accrued to the trial. Solid phase extraction and mass spectroscopy were used to evaluate parthenolide plasma concentrations. The limit of detection for parthenolide in plasma was 0.5 ng/ml. Patients were evaluated for response after every two cycles.


RESULTS
Feverfew given on this schedule had no significant toxicity, and the maximum tolerated dose was not reached. When parthenolide was administered at doses up to 4 mg as a daily oral capsule in the feverfew preparation, there was not detectable concentration in the plasma. Because of this, parthenolide pharmacokinetics were not able to be completed.


CONCLUSIONS
Feverfew, with up to 4 mg of parthenolide, given daily as an oral tablet is well tolerated without dose-limiting toxicity, but does not provide detectable plasma concentrations. Purification of parthenolide for administration of higher doses will be needed.
Curry
Eardie A
EA
Department of Pharmacy Practice, Purdue University, Indianapolis, IN, USA.
Murry
Daryl J
DJ
Yoder
Christy
C
Fife
Karen
K
Armstrong
Victoria
V
Nakshatri
Harikrishna
H
O'Connell
Michael
M
Sweeney
Christopher J
CJ
D000284:Administration, Oral; D000368:Aged; D000369:Aged, 80 and over; D000972:Antineoplastic Agents, Phytogenic / Q000097:blood*; D002851:Chromatography, High Pressure Liquid; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005260:Female; D006801:Humans; D008297:Male; D013058:Mass Spectrometry; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy*; D008517:Phytotherapy; D028321:Plant Preparations / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics*; D012717:Sesquiterpenes / Q000097:blood*; D020903:Tanacetum parthenium / Q000737:chemistry*
D000972:Antineoplastic Agents, Phytogenic; D028321:Plant Preparations; D012717:Sesquiterpenes; C002669:parthenolide