A prospective phase II study of 2-methoxyestradiol administered in combination with bevacizumab in patients with metastatic carcinoid tumors

Cancer Chemother Pharmacol. 2011 Aug;68(2):293-300. doi: 10.1007/s00280-010-1478-7. Epub 2010 Oct 20.


Purpose: Angiogenesis inhibition has emerged as a potentially promising treatment strategy for neuroendocrine tumors. 2-Methoxyestradiol (2ME2; Panzem(®)) is a natural derivative of estradiol with demonstrated anti-angiogenic activity in animal models. We performed a prospective, phase II study of 2ME2, administered in combination with bevacizumab, in patients with advanced carcinoid tumors.

Methods: Thirty-one patients with advanced carcinoid tumors were treated with 2ME2, administered orally at a dose of 1,000 mg four times daily. Patients also received bevacizumab 5 mg/kg intravenously every 2 weeks. Patients were observed for evidence of toxicity, tumor response, and survival.

Results: The combination of 2ME2 and bevacizumab was relatively easily tolerated and was associated with anticipated toxicities for these two agents. No confirmed radiologic responses (by RECIST) were observed. However, 68% of the radiologically evaluable patients experienced at least some degree of tumor reduction, and the median progression-free survival (PFS) time was 11.3 months.

Conclusion: 2ME2 and bevacizumab can be safely administered to patients with advanced carcinoid tumors. While major tumor regression was not observed with this regimen, the encouraging median progression-free survival time suggests that this regimen has some degree of antitumor activity and supports the further investigation of angiogenesis inhibitors in this disease.

Publication types

  • Clinical Trial, Phase II
  • Research Support, N.I.H., Extramural

MeSH terms

  • 2-Methoxyestradiol
  • Adult
  • Aged
  • Angiogenesis Inhibitors / administration & dosage
  • Angiogenesis Inhibitors / adverse effects
  • Angiogenesis Inhibitors / pharmacokinetics
  • Angiogenesis Inhibitors / therapeutic use*
  • Antibodies, Monoclonal / administration & dosage
  • Antibodies, Monoclonal / adverse effects
  • Antibodies, Monoclonal / therapeutic use*
  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / pharmacokinetics
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Bevacizumab
  • Carcinoid Tumor / blood
  • Carcinoid Tumor / drug therapy*
  • Carcinoid Tumor / pathology
  • Carcinoid Tumor / secondary*
  • Cohort Studies
  • Estradiol / administration & dosage
  • Estradiol / adverse effects
  • Estradiol / analogs & derivatives*
  • Estradiol / pharmacokinetics
  • Estradiol / therapeutic use
  • Female
  • Gastrointestinal Neoplasms / blood
  • Gastrointestinal Neoplasms / drug therapy
  • Gastrointestinal Neoplasms / pathology
  • Humans
  • Hydroxyestrones / blood
  • Male
  • Middle Aged
  • Neoplasm Staging
  • Patient Dropouts
  • Survival Analysis
  • Tumor Burden / drug effects
  • Vascular Endothelial Growth Factor A / antagonists & inhibitors


  • Angiogenesis Inhibitors
  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Hydroxyestrones
  • Vascular Endothelial Growth Factor A
  • Bevacizumab
  • Estradiol
  • 2-Methoxyestradiol
  • 2-methoxyestrone