Bevacizumab combination therapy in recurrent, platinum-refractory, epithelial ovarian carcinoma: A retrospective analysis.
BACKGROUND
The study was undertaken to determine the safety and efficacy of the monoclonal, antivascular endothelial growth factor antibody bevacizumab in combination with cytotoxic chemotherapy for women with platinum-refractory ovarian cancer.


METHODS
A retrospective analysis of women who received bevacizumab in combination with a cytotoxic agent was performed. Response was determined by measurable disease or assessment of serial cancer antigen (CA) 125 measurements.


RESULTS
Twenty-three patients were identified. The patients were heavily pretreated with a median of 7 prior regimens including a median of 3 prior platinum regimens. The combination regimen included cyclophosphamide in 15 (65%), 5-fluorouracil (5-FU) in 6 (26%), docetaxel in 1 (4%), and gemcitibine/liposomal doxorubicin in 1 (4%). Two (9%) women developed chylous ascites during treatment. CTC Grade 4-5 toxicities occurred in 4 (17%) subjects. Gastrointestinal perforation occurred in 2 (9%) patients. Measurable disease was present in 22. The overall best response rate was 35% and all 8 were partial responses (PRs). Stable disease was found in a further 10 (44%) women, whereas progressive disease was observed in 5 (22%). The median time to progression was 5.6 months in patients with a PR and 2.3 months in subjects with stable disease. Three (13%) women experienced a progression-free interval (PFI) of >6 months. At last follow-up, 8 (35%) subjects had died of disease, whereas 15 (65%) women were alive with disease.


CONCLUSIONS
Combination bevacizumab therapy demonstrated activity in heavily pretreated women with ovarian cancer. Gastrointestinal perforations were identified in 9%. Despite the toxicity of the regimen, prospective studies, particularly in less heavily pretreated patients, are warranted.
Wright
Jason D
JD
Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Washington University School of Medicine, St. Louis, Missouri 63110, USA. wrightj@msnotes.wustl.edu
Hagemann
Andrea
A
Rader
Janet S
JS
Viviano
Dana
D
Gibb
Randall K
RK
Norris
Lori
L
Mutch
David G
DG
Powell
Matthew A
MA
D000328:Adult; D000368:Aged; D020533:Angiogenesis Inhibitors / Q000009:adverse effects / Q000627:therapeutic use; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D000068258:Bevacizumab; D015331:Cohort Studies; D003520:Cyclophosphamide / Q000008:administration & dosage; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D000077143:Docetaxel; D004317:Doxorubicin / Q000008:administration & dosage; D019008:Drug Resistance, Neoplasm; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D007416:Intestinal Perforation / Q000139:chemically induced; D008875:Middle Aged; D009375:Neoplasms, Glandular and Epithelial / Q000188:drug therapy*; D010051:Ovarian Neoplasms / Q000188:drug therapy*; D017671:Platinum Compounds / Q000008:administration & dosage; D012189:Retrospective Studies; D043823:Taxoids / Q000008:administration & dosage; D015898:Tomography Scanners, X-Ray Computed; D016896:Treatment Outcome; D000093542:Gemcitabine
D020533:Angiogenesis Inhibitors; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D017671:Platinum Compounds; D043823:Taxoids; D003841:Deoxycytidine; D000077143:Docetaxel; D000068258:Bevacizumab; D004317:Doxorubicin; D003520:Cyclophosphamide; D005472:Fluorouracil; D000093542:Gemcitabine