title: Farletuzumab (a monoclonal antibody against folate receptor alpha) in relapsed platinum-sensitive ovarian cancer.
abstract: OBJECTIVE
  Farletuzumab is a humanized monoclonal antibody to folate receptor-α, which is over-expressed in most epithelial ovarian cancers but largely absent on normal tissue. We evaluated clinical activity of farletuzumab, alone and combined with chemotherapy, in women with first-relapse, platinum-sensitive ovarian, fallopian tube and primary peritoneal cancers.
  
  
  METHODS
  Fifty-four eligible subjects received open-label farletuzumab weekly, single agent or combined with carboplatin (AUC5-6) and taxane (paclitaxel 175 mg/m(2) or docetaxel 75 mg/m(2)), every 21 days for 6 cycles, followed by farletuzumab maintenance until progression. Twenty-eight subjects with asymptomatic CA125 relapse received single-agent farletuzumab and could receive platinum/taxane chemotherapy plus farletuzumab after single-agent progression. Twenty-six subjects with symptomatic relapse entered the combination arm directly; 21 subjects entered after single agent. Primary endpoints included normalized CA125 and Overall Response Rate (ORR). Duration of each subject's second progression-free interval (PFI2) was compared with her own first response interval (PFI1).
  
  
  RESULTS
  Farletuzumab was well-tolerated as single agent, without additive toxicity when administered with chemotherapy. Of 47 subjects who received farletuzumab with chemotherapy, 38 (80.9%) normalized CA125. In 9/42 (21%) evaluable subjects, PFI2 was≥PFI1, better than the historical rate (3%). There was a high response rate among subjects with PFI1 <12 months (75%), comparable to that in subjects with PFI1 ≥12 months (84%). Complete or partial ORR was 75% with combination therapy.
  
  
  CONCLUSIONS
  Based on this study, farletuzumab with carboplatin and taxane may enhance the response rate and duration of response in platinum-sensitive ovarian cancer patients with first relapse after remission of 6-18 months.
authors.affiliation: Medical Oncology, Johns Hopkins Kimmel Cancer Center, Baltimore, MD, USA.
authors.forename: Deborah K
authors.initials: DK
authors.lastname: Armstrong
authors.forename: Allen J
authors.initials: AJ
authors.lastname: White
authors.forename: Susan C
authors.initials: SC
authors.lastname: Weil
authors.forename: Martin
authors.initials: M
authors.lastname: Phillips
authors.forename: Robert L
authors.initials: RL
authors.lastname: Coleman
mesh_terms: D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage / Q000009:adverse effects; D000077216:Carcinoma, Ovarian Epithelial; D018572:Disease-Free Survival; D000077143:Docetaxel; D004342:Drug Hypersensitivity / Q000209:etiology; D005185:Fallopian Tube Neoplasms / Q000188:drug therapy / Q000276:immunology; D005260:Female; D006801:Humans; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy / Q000276:immunology; D009375:Neoplasms, Glandular and Epithelial / Q000188:drug therapy* / Q000276:immunology; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000276:immunology; D017239:Paclitaxel / Q000008:administration & dosage / Q000009:adverse effects; D010534:Peritoneal Neoplasms / Q000188:drug therapy / Q000276:immunology; D043823:Taxoids / Q000008:administration & dosage / Q000009:adverse effects
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D043823:Taxoids; D000077143:Docetaxel; C527484:farletuzumab; D016190:Carboplatin; D017239:Paclitaxel