A phase I dose-escalation, safety and pharmacokinetic study of the 2-methoxyestradiol analog ENMD-1198 administered orally to patients with advanced cancer

Investigational New Drugs

Volumn 29, Issue 2, 2011, Pages 340-346

  Zhou, Qing ^a,b   Gustafson, Daniel ^a   Nallapareddy, Sujatha ^a   Diab, Sami ^a   Leong, Stephen ^a   Lewis, Karl ^a   Gore, Lia ^a   Messersmith, Wells A ^a   Treston, Anthony M ^c   Eckhardt, S Gail ^a   Sidor, Carolyn ^c   Camidge, D Ross ^a,d  

^a UNIVERSITY OF COLORADO SCHOOL OF MEDICINE   (United States)

^b GUANGDONG PROVINCIAL PEOPLE'S HOSPITAL   (China)

^c EntreMed Inc   (United States)

^d UNIVERSITY OF COLORADO CANCER CENTER   (United States)

Author keywords

ENMD 1198; Pharmacokinetics; Phase I

Indexed keywords

2 METHOXYESTRA 1,3,5 [10] 16 TETRAENE 3 CARBOXAMIDE; 2 METHOXYESTRADIOL; ENMD 1198; UNCLASSIFIED DRUG; 2 METHOXYOESTRA 1,3,5(10),16 TETRAENE 3 CARBOXAMIDE; 2-METHOXYESTRADIOL; 2-METHOXYOESTRA-1,3,5(10),16-TETRAENE-3-CARBOXAMIDE; ANTINEOPLASTIC AGENT; DRUG DERIVATIVE; ESTRADIOL; ESTRANE DERIVATIVE;

ADULT; ADVANCED CANCER; AGED; ALOPECIA; ANEMIA; ANOREXIA; ANTINEOPLASTIC ACTIVITY; AREA UNDER THE CURVE; ARTICLE; CANCER CHEMOTHERAPY; CLINICAL ARTICLE; CONSTIPATION; CONTROLLED STUDY; DIARRHEA; DRUG BLOOD LEVEL; DRUG CLEARANCE; DRUG DISTRIBUTION; DRUG DOSE COMPARISON; DRUG ELIMINATION; DRUG HALF LIFE; DRUG SAFETY; DRUG TOLERABILITY; FATIGUE; FEMALE; GASTROESOPHAGEAL REFLUX; HOT FLUSH; HUMAN; HYPOTENSION; MALE; MAXIMUM PLASMA CONCENTRATION; MAXIMUM TOLERATED DOSE; MESOTHELIOMA; MULTIPLE CYCLE TREATMENT; NAUSEA AND VOMITING; NEUROENDOCRINE TUMOR; NEUROPATHY; NEUTROPENIA; OVARY CANCER; PANCREAS CARCINOMA; PHASE 1 CLINICAL TRIAL; PRIORITY JOURNAL; PROSTATE CANCER; TASTE DISORDER; THROMBOCYTOPENIA; TIME TO MAXIMUM PLASMA CONCENTRATION; ANIMAL; BLOOD; CLINICAL TRIAL; DEMOGRAPHY; DOG; DOSE RESPONSE; MIDDLE AGED; NEOPLASM; ORAL DRUG ADMINISTRATION; RAT; SPECIES DIFFERENCE;

ADMINISTRATION, ORAL; ADULT; AGED; ANIMALS; ANTINEOPLASTIC AGENTS; DEMOGRAPHY; DOGS; DOSE-RESPONSE RELATIONSHIP, DRUG; ESTRADIOL; ESTRENES; FEMALE; HUMANS; MALE; MIDDLE AGED; NEOPLASMS; RATS; SPECIES SPECIFICITY;

EID: 79955986877     PISSN: 01676997     EISSN: 15730646     Source Type: Journal    
DOI: 10.1007/s10637-009-9383-9     Document Type: Article

References (16)

1. LaVallee TM, Zhan XH, Johnson MS et al (2003) 2- Methoxyestradiol up-regulates death receptor 5 and induces apoptosis through activation of the extrinsic pathway. Cancer Res 63:468-475 (Pubitemid 36152509)
2. Mabjeesh NJ, Escuin D, LaVallee TM et al (2003) 2ME2 inhibits tumor growth and angiogenesis by disrupting microtubules and dysregulating HIF. Cancer Cell 3:363-375 (Pubitemid 38340305)
3. FotsisT ZhangY, Pepper MS et al (1994) The endogenous oestrogen metabolite 2-methoxyoestradiol inhibits angiogenesis and suppresses tumour growth. Nature 368:237-239 (Pubitemid 24108838)
4. Mooberry SL (2003) Mechanism of action of 2-methoxyestradiol: new developments. Drug Resist Updat 6:355-361 (Pubitemid 38173586)
5. James J, Murry DJ, Treston AM et al (2007) Phase I safety, pharmacokinetic and pharmacodynamic studies of 2-methoxyestradiol alone or in combinationwith docetaxel in patients with locally recurrent or metastatic breast cancer. Invest New Drugs 25:41-48 (Pubitemid 44657641)
6. Kawashima Y (2001) Nanoparticulate systems for improved drug delivery. Adv Drug Deliv Rev 47:1-2 (Pubitemid 32209228)
7. Merisko-Liversidge E, Sarpotdar P, Bruno J et al (1996) Formulation and antitumor activity evaluation ofnanocrystalline suspensions of poorly soluble anticancer drugs. Pharm Res 13:272-278 (Pubitemid 26074194)
8. Fogler WE, Volker K, Swartz GM et al (2006) The antitumor activity of 2-methoxyestradiol is maximized by maintaining a threshold concentration over a 24-hour dosing interval. Proceedings of the AACR-NCIEORTC International Conference on Molecular Targets and Cancer Therapeutics, Washington DC B180:173
9. Matei D, Schilder J, Sutton G et al (2009) Activity of 2 methoxyestradiol (Panzem NCD) in advanced, platinum-resistant ovarian cancer and primary peritoneal carcinomatosis: a Hoosier oncology group trial. Gynecol Oncol 115:90-96
10. LaVallee TM, Burke PA, Swartz GM et al (2008) Significant antitumor activity in vivo following treatment with the microtubule agent ENMD-1198. Mol Cancer Ther 7:1472-1482
11. Moser C, Lang SA, Mori A et al (2008) ENMD-1198, a novel tubulin-binding agent reduces HIF-1alpha and STAT3 activity in human hepatocellular carcinoma(HCC) cells, and inhibits growth and vascularization in vivo. BMC Cancer 8:206-217
12. Becker CM, Rohwer N, Funakoshi T et al (2008) 2- methoxyestradiol inhibits hypoxia-inducible factor-1{alpha} and suppresses growth of lesions in a mouse model of endometriosis. Am J Pathol 172:534-544 (Pubitemid 351282038)
13. Ricker JL, Chen Z, Yang XP et al (2004) 2-methoxyestradiol inhibits hypoxia-inducible factor 1alpha, tumor growth, and angiogenesis and augments paclitaxel efficacy in head and neck squamous cell carcinoma. Clin Cancer Res 10:8665-8673 (Pubitemid 40053435)
14. Burke PA, Chen XR, Waters CL et al (2006) In vitro and in vivo mechanisms of action for the antitumor activity of the microtubule destabilizing agent ENMD-1198 include inhibition of HIF-1α, NF-κB and Stat3. AACR Abstract #491. http://aacrmeeting abstracts.org/cgi/content/abstract/2006/1/116
15. LaVallee TM, Swartz GM, Strawn S et al (2005) Antitumor activity and preclinical toxicity for microtubule destabilizing agent ENMD-1198.Proceedings of the AACR-NCI-EORTC International Conference, Molecular Targets and Cancer Therapeutics, B240, page 188
16. Tevaarwerk AJ, Holen KD, Alberti DB et al (2009) Phase I trial of 2-methoxyestradiol NanoCrystal dispersion in advanced solid malignancies. Clin Cancer Res 15:1460-1465