Cancer Chemotherapy and Pharmacology

, Volume 68, Issue 2, pp 293–300

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

  • Matthew H. Kulke
  • Jennifer A. Chan
  • Jeffrey A. Meyerhardt
  • Andrew X. Zhu
  • Thomas A. Abrams
  • Lawrence S. Blaszkowsky
  • Eileen Regan
  • Carolyn Sidor
  • Charles S. Fuchs
Original Article

DOI: 10.1007/s00280-010-1478-7

Cite this article as:
Kulke, M.H., Chan, J.A., Meyerhardt, J.A. et al. Cancer Chemother Pharmacol (2011) 68: 293. doi:10.1007/s00280-010-1478-7

Abstract

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.

Keywords

Carcinoid Neuroendocrine Tumors Bevacizumab Sorafenib 

Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  • Matthew H. Kulke
    • 1
  • Jennifer A. Chan
    • 1
  • Jeffrey A. Meyerhardt
    • 1
  • Andrew X. Zhu
    • 2
  • Thomas A. Abrams
    • 1
  • Lawrence S. Blaszkowsky
    • 2
  • Eileen Regan
    • 1
  • Carolyn Sidor
    • 3
  • Charles S. Fuchs
    • 1
  1. 1.Dana-Farber Cancer InstituteBostonUSA
  2. 2.Massachusetts General HospitalBostonUSA
  3. 3.EntreMed, IncRockvilleUSA

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