Activity of 2 methoxyestradiol (Panzem® NCD) in advanced, platinum-resistant ovarian cancer and primary peritoneal carcinomatosis

A Hoosier Oncology Group trial

Daniela Matei, Jeanne Schilder, Gregory Sutton, Susan Perkins, Tim Breen, Check Quon, Carolyn Sidor

Research output: Contribution to journalArticle

66 Citations (Scopus)

Abstract

Background: 2-Methoxyestradiol (Panzem®, 2ME2) is an endogenous metabolite of estradiol that destabilizes microtubules and exerts anti-angiogenic properties. This study was conducted to determine the activity and safety of 2ME2 administered as a NanoCrystal® dispersion (NCD) formulation in patients with recurrent, platinum-resistant epithelial ovarian cancer (EOC). Methods: Eligible patients had relapsed, platinum-resistant or refractory EOC with measurable or detectable disease. There was no limit on the number of prior treatment regimens. 2ME2 NCD 1000 mg orally four times daily (q.i.d.) was administered continuously during 4 week cycles. The primary endpoint was objective response rate (ORR). Secondary endpoints were assessment of toxicity, rate of clinical benefit defined as the number of patients experiencing an objective response, a CA125 response or stable disease (SD) > 3 months, mean change in CA-125, progression-free survival (PFS), and pharmacokinetic analyses of 2ME2. Results: Eighteen patients were enrolled. Median age was 65.5 (range 40-73). Patients had received a median of five prior treatments. The most common adverse events were fatigue (78%), nausea (78%), diarrhea (39%), neuropathy (50%), edema (39%), and dyspnea (44%), the majority being grade 1-2. There were no objective responses, but seven patients had SD as best response. Of those, two patients had SD for greater than 12 months. The rate of clinical benefit was 31.3%. Fairly stable plasma levels of 2ME2 ranging within the predicted therapeutic window were observed. Conclusions: The NCD formulation of 2ME2 is well tolerated in patients with heavily pretreated EOC. Few of these heavily pretreated patients had sustained stable disease.

Original languageEnglish
Pages (from-to)90-96
Number of pages7
JournalGynecologic Oncology
Volume115
Issue number1
DOIs
StatePublished - Oct 2009

Fingerprint

Platinum
Ovarian Neoplasms
Nanoparticles
Carcinoma
2-methoxyestradiol
Survival Analysis
Microtubules
Dyspnea
Nausea
Disease-Free Survival
Fatigue
Estradiol
Diarrhea
Edema
Therapeutics
Pharmacokinetics
Safety

Keywords

  • 2-methoxyestradiol
  • Angiogenesis
  • Clinical trial
  • Ovarian cancer

ASJC Scopus subject areas

  • Obstetrics and Gynecology
  • Oncology

Cite this

Activity of 2 methoxyestradiol (Panzem® NCD) in advanced, platinum-resistant ovarian cancer and primary peritoneal carcinomatosis : A Hoosier Oncology Group trial. / Matei, Daniela; Schilder, Jeanne; Sutton, Gregory; Perkins, Susan; Breen, Tim; Quon, Check; Sidor, Carolyn.

In: Gynecologic Oncology, Vol. 115, No. 1, 10.2009, p. 90-96.

Research output: Contribution to journalArticle

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abstract = "Background: 2-Methoxyestradiol (Panzem{\circledR}, 2ME2) is an endogenous metabolite of estradiol that destabilizes microtubules and exerts anti-angiogenic properties. This study was conducted to determine the activity and safety of 2ME2 administered as a NanoCrystal{\circledR} dispersion (NCD) formulation in patients with recurrent, platinum-resistant epithelial ovarian cancer (EOC). Methods: Eligible patients had relapsed, platinum-resistant or refractory EOC with measurable or detectable disease. There was no limit on the number of prior treatment regimens. 2ME2 NCD 1000 mg orally four times daily (q.i.d.) was administered continuously during 4 week cycles. The primary endpoint was objective response rate (ORR). Secondary endpoints were assessment of toxicity, rate of clinical benefit defined as the number of patients experiencing an objective response, a CA125 response or stable disease (SD) > 3 months, mean change in CA-125, progression-free survival (PFS), and pharmacokinetic analyses of 2ME2. Results: Eighteen patients were enrolled. Median age was 65.5 (range 40-73). Patients had received a median of five prior treatments. The most common adverse events were fatigue (78{\%}), nausea (78{\%}), diarrhea (39{\%}), neuropathy (50{\%}), edema (39{\%}), and dyspnea (44{\%}), the majority being grade 1-2. There were no objective responses, but seven patients had SD as best response. Of those, two patients had SD for greater than 12 months. The rate of clinical benefit was 31.3{\%}. Fairly stable plasma levels of 2ME2 ranging within the predicted therapeutic window were observed. Conclusions: The NCD formulation of 2ME2 is well tolerated in patients with heavily pretreated EOC. Few of these heavily pretreated patients had sustained stable disease.",
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AU - Sidor, Carolyn

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