Advertisement
Journal of Clinical Oncology  
Search for:
Limit by:
  Browse by Subject or Issue
Home Search or Browse JCO My JCO Subscriptions Customer Service Site Map

Journal of Clinical Oncology, Vol 26, No 1 (January 1), 2008: pp. 76-82
© 2008 American Society of Clinical Oncology.
DOI: 10.1200/JCO.2007.12.1939

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Purchase Article
Right arrow View Shopping Cart
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a colleague
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Save to my personal folders
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Garcia, A. A.
Right arrow Articles by Oza, A. M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Garcia, A. A.
Right arrow Articles by Oza, A. M.

Phase II Clinical Trial of Bevacizumab and Low-Dose Metronomic Oral Cyclophosphamide in Recurrent Ovarian Cancer: A Trial of the California, Chicago, and Princess Margaret Hospital Phase II Consortia

Agustin A. Garcia, Hal Hirte, Gini Fleming, Dongyun Yang, Denice D. Tsao-Wei, Lynda Roman, Susan Groshen, Steve Swenson, Frank Markland, David Gandara, Sidney Scudder, Robert Morgan, Helen Chen, Heinz-Josef Lenz, Amit M. Oza

From the University of Southern California/Norris Comprehensive Cancer Center, Los Angeles; University of California Davis School of Medicine, Sacramento; City of Hope Comprehensive Cancer Center, Duarte, CA; University of Chicago, Chicago, IL; National Cancer Institute, Bethesda, MD; Juravinski Cancer Center, Hamilton; and the Princess Margaret Hospital, Toronto, Ontario, Canada

Corresponding author: Agustin A. Garcia, MD, University of Southern California, Norris Comprehensive Cancer Center, 1441 Eastlake Ave, MS 34, Los Angeles, CA 90033; e-mail: aagarcia{at}usc.edu

Purpose: Vascular endothelial growth factor (VEGF) plays an important role in the biology of ovarian cancer (OC). Inhibitors of VEGF suppress tumor growth in OC models. Metronomic chemotherapy, defined as frequent administration of low doses of cytotoxic chemotherapy, suppresses tumor growth, possibly by inhibiting angiogenesis. A phase II trial was conducted to evaluate the antitumor activity and adverse effects of bevacizumab and metronomic oral cyclophosphamide in women with recurrent OC.

Patients and Methods: Patients with measurable disease and prior treatment with a platinum-containing regimen were eligible. Up to two different regimens for recurrent disease were allowed. Treatment consisted of bevacizumab 10 mg/kg intravenously every 2 weeks and oral cyclophosphamide 50 mg/d. The primary end point was progression-free survival at 6 months. Plasma levels of VEGF, E-selectin, and thrombospondin-1 were obtained serially.

Results: Seventy patients were enrolled. The probability of being alive and progression free at 6 months was 56% (± 6% SE). A partial response was achieved in 17 patients (24%). Median time to progression and survival were 7.2 and 16.9 months, respectively. The most common serious toxicities were hypertension, fatigue, and pain. Bevacizumab-related toxicities included four episodes of gastrointestinal perforation or fistula, two episodes each of CNS ischemia and pulmonary hypertension, and one episode each of gastrointestinal bleeding and wound healing complication. There were three treatment-related deaths. Levels of VEGF, E-selectin, and thrombospondin-1 were not associated with clinical outcome.

Conclusion: The combination of bevacizumab and metronomic cyclophosphamide is active in recurrent OC. Further study of this combination is warranted.

Supported by National Cancer Institute Grants No. P30 CA 14089, N01 CM62209, CM17107, CM-17102, and CM62203, and by the Ovarian Cancer Coalition of Greater California. This trial was sponsored by Cancer Therapy Evaluation Program of the National Cancer Institute under the Collaborative Research and Development Agreement between the National Cancer Institute and Genentech Inc.

Presented in part at the 41st and 42nd Annual Meetings of the American Society of Clinical Oncology, Orlando, FL, May 13-15, 2005, and Atlanta, GA, June 2-6, 2006.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.




This article has been cited by other articles:


Home page
NEJMHome page
R. S. Kerbel
Tumor Angiogenesis
N. Engl. J. Med., May 8, 2008; 358(19): 2039 - 2049.
[Full Text] [PDF]



About
JCO
 Editorial
Roster
 Advertising
Information
 Librarians &
Institutions
 Rights &
Permissions
 PDA Services

Copyright © 2008 by the American Society of Clinical Oncology, Online ISSN: 1527-7755. Print ISSN: 0732-183X
Terms and Conditions of Use
  HighWire Press HighWire Press™ assists in the publication of JCO Online