title: Combined weekly topotecan and biweekly bevacizumab in women with platinum-resistant ovarian, peritoneal, or fallopian tube cancer: results of a phase 2 study.
abstract: BACKGROUND
  A phase 2 trial was conducted to determine the toxicity and efficacy of combined weekly topotecan and biweekly bevacizumab in patients with primary or secondary platinum-resistant ovarian, peritoneal, or fallopian tube cancer (OC).
  
  
  METHODS
  Patients were treated with bevacizumab 10 mg/kg on days 1 and 15 and topotecan 4 mg/m(2) on days 1, 8, and 15 of a 28-day cycle until progressive disease (PD) or excessive toxicity. The primary endpoint was progression-free survival (PFS); secondary objectives included overall survival (OS), objective response, and toxicity.
  
  
  RESULTS
  Patients (N = 40) received a median of 8 treatment cycles. Toxicity was generally mild or moderate, with neutropenia (18%), hypertension (20%), gastrointestinal toxicity (18%), pain (13%), metabolic toxicity (15%), bowel obstruction (10%), and cardiotoxicity (8%) being the most common grade 3 and 4 adverse events. No bowel perforations, febrile neutropenia, or treatment-related deaths occurred. Median PFS and OS were 7.8 (95% confidence interval [CI], 3.0-9.4) and 16.6 months (95% CI, 12.8-22.9), with 22 (55%) patients progression-free for ≥6 months. Ten (25%) patients had partial response (PR), 14 (35%) had stable disease (SD), and 16 (40%) had PD. Patients treated with 2 prior regimens received greater benefit than patients treated with 1: PR/SD, 78.9% versus 42.9% (P = .03); median PFS, 10.9 versus 2.8 months (P = .08); median OS, 22.9 versus 12.8 months (P = .02).
  
  
  CONCLUSIONS
  A weekly topotecan and biweekly bevacizumab combination demonstrates acceptable toxicity and encouraging efficacy in patients with platinum-resistant OC; further study is warranted.
authors.affiliation: Women's Cancer Care of Seattle, Seattle, Washington 98133, USA. kathryn.mcgonigle@nwhsea.org
authors.forename: Kathryn F
authors.initials: KF
authors.lastname: McGonigle
authors.forename: Howard G
authors.initials: HG
authors.lastname: Muntz
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Vuky
authors.forename: Pamela J
authors.initials: PJ
authors.lastname: Paley
authors.forename: Dan S
authors.initials: DS
authors.lastname: Veljovich
authors.forename: Benjamin E
authors.initials: BE
authors.lastname: Greer
authors.forename: Barbara A
authors.initials: BA
authors.lastname: Goff
authors.forename: Heidi J
authors.initials: HJ
authors.lastname: Gray
authors.forename: Thomas W
authors.initials: TW
authors.lastname: Malpass
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D000068258:Bevacizumab; D004334:Drug Administration Schedule; D019008:Drug Resistance, Neoplasm; D005185:Fallopian Tube Neoplasms / Q000188:drug therapy*; D005260:Female; D006801:Humans; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000188:drug therapy*; D010534:Peritoneal Neoplasms / Q000188:drug therapy*; D017671:Platinum Compounds / Q000494:pharmacology; D019772:Topotecan / Q000008:administration & dosage*
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D017671:Platinum Compounds; D000068258:Bevacizumab; D019772:Topotecan