title: Multicenter phase II trial of topotecan, cisplatin and bevacizumab for recurrent or persistent cervical cancer.
abstract: OBJECTIVE
  We evaluated the activity and safety of the combination of topotecan, cisplatin and bevacizumab in patients with recurrent or persistent carcinoma of the cervix.
  
  
  METHODS
  Eligible patients had persistent or recurrent cervical cancer not amenable to curative intent treatment. No prior chemotherapy for recurrence was allowed. Treatment consisted of cisplatin 50 mg/m(2) day 1, topotecan 0.75 mg/m(2) days 1, 2 and 3 and bevacizumab 15 mg/kgday 1 every 21 days until disease progression or limiting toxicity. The primary endpoint was progression free survival at 6 months. We explored PET/CT as a potential early indicator of response to therapy.
  
  
  RESULTS
  Twenty-seven eligible patients received a median of 3 treatment cycles (range, 1-19). Median follow-up was 10 months (range, 1.7-33.4). The 6-month PFS was 59% (80% CI: 46-70%). In 26 evaluable patients, we observed 1 CR (4%; 80% CI: 0.4-14%) and 8 PR (31%; 80% CI: 19-45%) lasting a median of 4.4 months. Ten patients had SD (39%; 80% CI: 25-53%) with median duration of 2.2 months. Median PFS was 7.1 months (80% CI: 4.7-10.1) and median OS was 13.2 months (80% CI: 8.0-15.4). All patients were evaluated for toxicity. Grade 3-4 hematologic toxicity was common (thrombocytopenia 82% leukopenia 74%, anemia 63%, neutropenia 56%). Most patients (78%) required unanticipated hospital admissions for supportive care and/or management of toxicities.
  
  
  CONCLUSIONS
  The addition of bevacizumab to topotecan and cisplatin results in an active but highly toxic regimen. Future efforts should focus on identification of predictive biomarkers of prolonged response and regimen modifications to minimize toxicity.
authors.affiliation: Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Washington University School of Medicine and Siteman Cancer Center, St. Louis, MO, USA. israel.zighelboim@sluhn.org
authors.forename: Israel
authors.initials: I
authors.lastname: Zighelboim
authors.forename: Jason D
authors.initials: JD
authors.lastname: Wright
authors.forename: Feng
authors.initials: F
authors.lastname: Gao
authors.forename: Ashley S
authors.initials: AS
authors.lastname: Case
authors.forename: L Stewart
authors.initials: LS
authors.lastname: Massad
authors.forename: David G
authors.initials: DG
authors.lastname: Mutch
authors.forename: Matthew A
authors.initials: MA
authors.lastname: Powell
authors.forename: Premal H
authors.initials: PH
authors.lastname: Thaker
authors.forename: Eric L
authors.initials: EL
authors.lastname: Eisenhauer
authors.forename: David E
authors.initials: DE
authors.lastname: Cohn
authors.forename: Fidel A
authors.initials: FA
authors.lastname: Valea
authors.forename: Angeles
authors.initials: A
authors.lastname: Alvarez Secord
authors.forename: Lynne T
authors.initials: LT
authors.lastname: Lippmann
authors.forename: Farrokh
authors.initials: F
authors.lastname: Dehdashti
authors.forename: Janet S
authors.initials: JS
authors.lastname: Rader
mesh_terms: D000328:Adult; D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D000068258:Bevacizumab; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D005260:Female; D019788:Fluorodeoxyglucose F18; D006801:Humans; D008875:Middle Aged; D064847:Multimodal Imaging; D009364:Neoplasm Recurrence, Local / Q000000981:diagnostic imaging / Q000188:drug therapy*; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals; D014057:Tomography, X-Ray Computed; D019772:Topotecan / Q000008:administration & dosage / Q000009:adverse effects; D002583:Uterine Cervical Neoplasms / Q000000981:diagnostic imaging / Q000188:drug therapy*; D055815:Young Adult
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18; D000068258:Bevacizumab; D019772:Topotecan; D002945:Cisplatin