title: Weekly ixabepilone with or without biweekly bevacizumab in the treatment of recurrent or persistent uterine and ovarian/primary peritoneal/fallopian tube cancers: A retrospective review.
abstract: OBJECTIVE
  To describe the clinical outcome and tolerability of weekly ixabepilone (16-20mg/m(2) days 1, 8, 15 of a 28-day cycle)±biweekly bevacizumab (10mg/kg days 1 and 15) in patients with recurrent/persistent uterine or ovarian/primary peritoneal/fallopian tube cancers.
  
  
  METHODS
  A single-institution retrospective review was performed inclusive of all patients who received ≥2cycles from 01/2010 to 06/2014. Progression-free (PFS) and overall (OS) survival were determined using the Kaplan-Meier method. Toxicities were graded according to CTCAEv4.0. Best response was categorized using RECIST or by CA-125 criteria.
  
  
  RESULTS
  A total of 60 patients (24 uterine and 36 ovarian cancers) were identified. Patients had received a median of 3.5 (range:1-10) prior lines of chemotherapy. Patients completed a mean of 4.7±2.9cycles of ixabepilone; 66.7% (16/24) and 91.7% (33/36) of patients with uterine and ovarian cancers received concurrent bevacizumab. For uterine cancers, objective response rate (ORR) was 41.7% (12.5% complete, 29.2% partial); median duration of response or stabilization was 7months (range:2-30). Median PFS and OS were 5.2 and 9.6months, respectively. PFS and OS were improved in the setting of concurrent bevacizumab (6.5 versus 3.0months, p=0.01, HR 0.2, 95% CI 0.05-0.77; 9.6 versus 4.2months, p=0.02, HR 0.58, 95% CI 0.04-0.74). Similar ORR was observed among ovarian cancers; median PFS/OS were not yet reached. Most toxicities were grade 1/2.
  
  
  CONCLUSIONS
  Weekly ixabepilone with or without biweekly bevacizumab has promising activity and acceptable toxicity in patients with platinum-/taxane-resistant endometrial and ovarian cancers. This combination warrants further prospective study in these populations.
authors: Yale University, Division of Gynecologic Oncology, Department of Obstetrics, Gynecology and Reproductive Sciences, P.O. Box 208063, New Haven, CT 06511, USA.
authors: Dana M
authors: DM
authors: Roque
authors: Yale University, Division of Gynecologic Oncology, Department of Obstetrics, Gynecology and Reproductive Sciences, P.O. Box 208063, New Haven, CT 06511, USA.
authors: Elena S
authors: ES
authors: Ratner
authors: Yale University, Division of Gynecologic Oncology, Department of Obstetrics, Gynecology and Reproductive Sciences, P.O. Box 208063, New Haven, CT 06511, USA.
authors: Dan-Arin
authors: DA
authors: Silasi
authors: Yale University, Division of Gynecologic Oncology, Department of Obstetrics, Gynecology and Reproductive Sciences, P.O. Box 208063, New Haven, CT 06511, USA.
authors: Masoud
authors: M
authors: Azodi
authors: Yale University, Division of Gynecologic Oncology, Department of Obstetrics, Gynecology and Reproductive Sciences, P.O. Box 208063, New Haven, CT 06511, USA.
authors: Thomas J
authors: TJ
authors: Rutherford
authors: Yale University, Division of Gynecologic Oncology, Department of Obstetrics, Gynecology and Reproductive Sciences, P.O. Box 208063, New Haven, CT 06511, USA.
authors: Peter E
authors: PE
authors: Schwartz
authors: Yale University, Division of Gynecologic Oncology, Department of Obstetrics, Gynecology and Reproductive Sciences, P.O. Box 208063, New Haven, CT 06511, USA.
authors: Wendelin K
authors: WK
authors: Nelson
authors: Yale University, Division of Gynecologic Oncology, Department of Obstetrics, Gynecology and Reproductive Sciences, P.O. Box 208063, New Haven, CT 06511, USA. Electronic address: alessandro.santin@yale.edu.
authors: Alessandro D
authors: AD
authors: Santin
mesh_terms: D020533:Angiogenesis Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D000068258:Bevacizumab; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D034261:Epothilones / Q000008:administration & dosage / Q000627:therapeutic use*; D005185:Fallopian Tube Neoplasms / Q000188:drug therapy*; D005260:Female; D006801:Humans; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy*; D010051:Ovarian Neoplasms / Q000188:drug therapy*; D010534:Peritoneal Neoplasms / Q000188:drug therapy*; D011446:Prospective Studies; D012189:Retrospective Studies
chemical_list: D020533:Angiogenesis Inhibitors; D061067:Antibodies, Monoclonal, Humanized; D034261:Epothilones; D000068258:Bevacizumab; C430592:ixabepilone
keywords: Bevacizumab; Endometrial cancer; Epothilone; Ixabepilone; Ovarian cancer; Recurrence; Taxane resistance