title: A multi-institutional evaluation of factors predictive of toxicity and efficacy of bevacizumab for recurrent ovarian cancer.
abstract: While bevacizumab has shown activity in recurrent ovarian cancer, a higher than expected incidence of bowel perforations has been reported in recent trials. We sought to determine factors associated with toxicity and tumor response in patients with relapsed ovarian cancer treated with bevacizumab. A retrospective review of patients with recurrent ovarian cancer treated with bevacizumab was undertaken. Response was determined radiographically and through CA125 measurements. Statistical analysis to determine factors associated with toxicity and response was performed. Sixty-two eligible patients were identified. The cohort had received a median of 5 prior chemotherapy regimens. Single-agent bevacizumab was administered to 12 (19%), while 50 (81%) received the drug in combination with a cytotoxic agent. Grade 3-5 toxicities occurred in 15 (24%) patients, including grade 3-4 hypertension in 4 (7%), gastrointestinal perforations in 7%, and chylous ascites in 5%. Development of chylous ascites and gastrointestinal perforations appeared to correlate with tumor response. The overall response rate was 36% (4 complete response, 17 partial response), with stable disease in 40%. A higher objective response rate was seen in the bevacizumab combination group compared to single-agent treatment (43% vs 10%) (P = 0.07). However, 29 grade 3-5 toxic episodes were seen in the combination group vs only 1 in the single-agent bevacizumab cohort (P = 0.071). We conclude that bevacizumab demonstrates promising activity in recurrent ovarian cancer. The addition of a cytotoxic agent to bevacizumab improved response rates at the cost of increased toxicity. Gastrointestinal perforations occurred in 7%. The perforations occurred in heavily pretreated patients who were responding to therapy.
authors.affiliation: Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Columbia University College of Physicians and Surgeons, New York, New York, USA.
authors.forename: J D
authors.initials: JD
authors.lastname: Wright
authors.forename: A A
authors.initials: AA
authors.lastname: Secord
authors.forename: T M
authors.initials: TM
authors.lastname: Numnum
authors.forename: R P
authors.initials: RP
authors.lastname: Rocconi
authors.forename: M A
authors.initials: MA
authors.lastname: Powell
authors.forename: A
authors.initials: A
authors.lastname: Berchuck
authors.forename: R D
authors.initials: RD
authors.lastname: Alvarez
authors.forename: R K
authors.initials: RK
authors.lastname: Gibb
authors.forename: K
authors.initials: K
authors.lastname: Trinkaus
authors.forename: J S
authors.initials: JS
authors.lastname: Rader
authors.forename: D G
authors.initials: DG
authors.lastname: Mutch
mesh_terms: D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D000740:Anemia / Q000139:chemically induced* / Q000453:epidemiology; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects*; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage; D000068258:Bevacizumab; D018450:Disease Progression; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007150:Immunohistochemistry; D016015:Logistic Models; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D009367:Neoplasm Staging; D009503:Neutropenia / Q000139:chemically induced* / Q000453:epidemiology; D010051:Ovarian Neoplasms / Q000401:mortality / Q000473:pathology* / Q000601:surgery; D010052:Ovariectomy; D011237:Predictive Value of Tests; D011336:Probability; D012189:Retrospective Studies; D018570:Risk Assessment; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab