Daniela Matei1, Jeanne Schilder2, Gregory Sutton3, Susan Perkins4, Tim Breen4, Check Quon5, Carolyn Sidor6. 1. Indiana University Department of Medicine, USA; Indiana University Department of Obstetrics and Gynecology, USA; Indiana University Melvin and Bren Cancer Center, USA; Indiana University School of Medicine, 535 Barnhill Drive, Indianapolis, IN, 46202, USA. Electronic address: dmatei@iupui.edu. 2. Indiana University Department of Obstetrics and Gynecology, USA; Indiana University School of Medicine, 535 Barnhill Drive, Indianapolis, IN, 46202, USA. 3. St. Vincent Gynecologic Oncology, USA; Indiana University School of Medicine, 535 Barnhill Drive, Indianapolis, IN, 46202, USA. 4. Indiana University Division of Biostatistics, USA; Indiana University School of Medicine, 535 Barnhill Drive, Indianapolis, IN, 46202, USA. 5. iNDa Consulting, Inc., Hockessin DE, USA; Indiana University School of Medicine, 535 Barnhill Drive, Indianapolis, IN, 46202, USA. 6. EntreMed, Inc., Rockville MD, USA; Indiana University School of Medicine, 535 Barnhill Drive, Indianapolis, IN, 46202, USA.
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.
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.
Authors: Marisol Quezada; Jorge Diaz; Soledad Henriquez; Maria Loreto Bravo; Evelyn Aranda; Barbara Oliva; Manuel Villalon; Sumie Kato; Mauricio A Cuello; Jan J Brosens; Carol A Lange; Gareth I Owen Journal: Horm Cancer Date: 2010-06 Impact factor: 3.869
Authors: Qing Zhou; Daniel Gustafson; Sujatha Nallapareddy; Sami Diab; Stephen Leong; Karl Lewis; Lia Gore; Wells A Messersmith; Anthony M Treston; S Gail Eckhardt; Carolyn Sidor; D Ross Camidge Journal: Invest New Drugs Date: 2010-01-19 Impact factor: 3.850
Authors: Gordon S Duncan; Dirk Brenner; Michael W Tusche; Anne Brüstle; Christiane B Knobbe; Andrew J Elia; Thomas Mock; Mark R Bray; Peter H Krammer; Tak W Mak Journal: Proc Natl Acad Sci U S A Date: 2012-12-03 Impact factor: 11.205