Phase I dose escalation trial of feverfew with standardized doses of parthenolide in patients with cancer

Eardie A. Curry, Daryl J. Murry, Christy Yoder, Karen Fife, Victoria Armstrong, Harikrishna Nakshatri, Michael O'Connell, Christopher J. Sweeney

Research output: Contribution to journalArticle

80 Citations (Scopus)

Abstract

Purpose: 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." Patients and methods: Feverfew (Tanacet™) 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 no detectable concentration in the plasma. Because of this, parthenolide pharmacokinetics were not able to be completed. Conclusion: 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.

Original languageEnglish
Pages (from-to)299-305
Number of pages7
JournalInvestigational New Drugs
Volume22
Issue number3
DOIs
StatePublished - Aug 2004

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Tanacetum parthenium
Neoplasms
Pharmacokinetics
Tablets
parthenolide
Maximum Tolerated Dose
Solid Phase Extraction
Capsules
Limit of Detection
Mass Spectrometry
Appointments and Schedules

Keywords

  • Feverfew
  • Parthenolide
  • Pharmacokinetics

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

Cite this

Phase I dose escalation trial of feverfew with standardized doses of parthenolide in patients with cancer. / Curry, Eardie A.; Murry, Daryl J.; Yoder, Christy; Fife, Karen; Armstrong, Victoria; Nakshatri, Harikrishna; O'Connell, Michael; Sweeney, Christopher J.

In: Investigational New Drugs, Vol. 22, No. 3, 08.2004, p. 299-305.

Research output: Contribution to journalArticle

Curry, Eardie A. ; Murry, Daryl J. ; Yoder, Christy ; Fife, Karen ; Armstrong, Victoria ; Nakshatri, Harikrishna ; O'Connell, Michael ; Sweeney, Christopher J. / Phase I dose escalation trial of feverfew with standardized doses of parthenolide in patients with cancer. In: Investigational New Drugs. 2004 ; Vol. 22, No. 3. pp. 299-305.
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N2 - Purpose: 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." Patients and methods: Feverfew (Tanacet™) 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 no detectable concentration in the plasma. Because of this, parthenolide pharmacokinetics were not able to be completed. Conclusion: 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.

AB - Purpose: 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." Patients and methods: Feverfew (Tanacet™) 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 no detectable concentration in the plasma. Because of this, parthenolide pharmacokinetics were not able to be completed. Conclusion: 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.

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