title: Farletuzumab, a humanized monoclonal antibody against folate receptor alpha, in epithelial ovarian cancer: a phase I study.
abstract: OBJECTIVE
  Folate receptor α expression is highly restricted in normal adult tissues but upregulated in a wide range of human cancer types, including epithelial ovarian cancer. Farletuzumab, a humanized monoclonal antibody against folate receptor α, has shown antitumor activity and favorable toxicity in preclinical evaluation. This phase I, dose-escalation study was conducted to determine the safety of weekly i.v. farletuzumab and establish the maximum tolerated dose (MTD).
  
  
  METHODS
  Patients with platinum-refractory or platinum-resistant epithelial ovarian cancer received farletuzumab (12.5-400 mg/m(2)) on days 1, 8, 15, and 22 of a 5-week cycle. Intrapatient dose escalation was not permitted. Dose-limiting toxicity (DLT) was defined by treatment-related adverse event of grade 3 or higher, and the MTD was the highest dose at which one or none of six patients experienced a DLT. Disease progression was recorded using Response Evaluation Criteria in Solid Tumors criteria and serum CA-125.
  
  
  RESULTS
  Twenty-five heavily pretreated patients were included in the safety, efficacy, and pharmacokinetic analyses. No DLTs or MTDs were encountered, and dose escalation was continued to farletuzumab 400 mg/m(2). C(max) and AUC(0-24) (area under the serum concentration-time curve) increased in an approximately dose-proportional manner, and a nuclear imaging substudy confirmed tumor targeting. There were no objective responses. Stable disease by Response Evaluation Criteria in Solid Tumors was observed in nine (36%) patients and CA-125 reduction in four. Three patients received continued therapy and completed a total of up to three cycles.
  
  
  CONCLUSIONS
  In this phase I study, farletuzumab administered as an i.v. infusion at doses of 12.5 to 400 mg/m(2) was generally safe and well tolerated in the management of heavily pretreated patients with epithelial ovarian cancer.
authors.affiliation: Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York 10065, USA. konnerj@mskcc.org
authors.forename: Jason A
authors.initials: JA
authors.lastname: Konner
authors.forename: Katherine M
authors.initials: KM
authors.lastname: Bell-McGuinn
authors.forename: Paul
authors.initials: P
authors.lastname: Sabbatini
authors.forename: Martee L
authors.initials: ML
authors.lastname: Hensley
authors.forename: William P
authors.initials: WP
authors.lastname: Tew
authors.forename: Neeta
authors.initials: N
authors.lastname: Pandit-Taskar
authors.forename: Nicholas
authors.initials: N
authors.lastname: Vander Els
authors.forename: Martin D
authors.initials: MD
authors.lastname: Phillips
authors.forename: Charles
authors.initials: C
authors.lastname: Schweizer
authors.forename: Susan C
authors.initials: SC
authors.lastname: Weil
authors.forename: Steven M
authors.initials: SM
authors.lastname: Larson
authors.forename: Lloyd J
authors.initials: LJ
authors.lastname: Old
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D002945:Cisplatin / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D019008:Drug Resistance, Neoplasm; D005260:Female; D058975:Folate Receptor 1 / Q000037:antagonists & inhibitors / Q000276:immunology*; D006801:Humans; D007167:Immunotherapy / Q000379:methods; D008875:Middle Aged; D009375:Neoplasms, Glandular and Epithelial / Q000378:metabolism / Q000628:therapy*; D010051:Ovarian Neoplasms / Q000378:metabolism / Q000628:therapy*; D017211:Treatment Failure; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D058975:Folate Receptor 1; C527484:farletuzumab; D002945:Cisplatin