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


CONCLUSIONS
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.
Dana-Farber Cancer Institute, Boston, MA 02115, USA. matthew_kulke@dfci.harvard.edu
Matthew H
MH
Kulke
Jennifer A
JA
Chan
Jeffrey A
JA
Meyerhardt
Andrew X
AX
Zhu
Thomas A
TA
Abrams
Lawrence S
LS
Blaszkowsky
Eileen
E
Regan
Carolyn
C
Sidor
Charles S
CS
Fuchs
D000077584:2-Methoxyestradiol; D000328:Adult; D000368:Aged; D020533:Angiogenesis Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000068258:Bevacizumab; D002276:Carcinoid Tumor / Q000097:blood / Q000188:drug therapy* / Q000473:pathology / Q000556:secondary*; D015331:Cohort Studies; D004958:Estradiol / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D005260:Female; D005770:Gastrointestinal Neoplasms / Q000097:blood / Q000188:drug therapy / Q000473:pathology; D006801:Humans; D006894:Hydroxyestrones / Q000097:blood; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D010352:Patient Dropouts; D016019:Survival Analysis; D047368:Tumor Burden / Q000187:drug effects; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors
D020533:Angiogenesis Inhibitors; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D006894:Hydroxyestrones; D042461:Vascular Endothelial Growth Factor A; D000068258:Bevacizumab; D004958:Estradiol; D000077584:2-Methoxyestradiol; C003655:2-methoxyestrone