title: Phase 1b safety study of farletuzumab, carboplatin and pegylated liposomal doxorubicin in patients with platinum-sensitive epithelial ovarian cancer.
abstract: OBJECTIVE
  Farletuzumab is a humanized monoclonal antibody that binds to folate receptor alpha, over-expressed in epithelial ovarian cancer (EOC) but largely absent in normal tissue. Previously, carboplatin plus pegylated liposomal doxorubicin showed superior progression-free survival and an improved therapeutic index compared with carboplatin/paclitaxel in relapsed platinum-sensitive EOC. This study assessed safety of farletuzumab/carboplatin/pegylated liposomal doxorubicin in women with platinum-sensitive recurrent EOC.
  
  
  METHODS
  This multicenter, single-arm study enrolled patients with platinum-sensitive EOC in first or second relapse for treatment with weekly farletuzumab 2.5mg/kg plus carboplatin AUC5-6 and pegylated liposomal doxorubicin 30mg/m(2) every 4weeks for 6cycles. Subsequently, maintenance with single-agent farletuzumab 2.5mg/kg once weekly or farletuzumab 7.5mg/kg once every three weeks continued until progression. The primary objective was to assess the safety of farletuzumab/carboplatin/pegylated liposomal doxorubicin.
  
  
  RESULTS
  Fifteen patients received a median of 12.0cycles (range, 3-26) of farletuzumab as combination therapy or maintenance, for a median of 45.0weeks (range 9-95). Farletuzumab/carboplatin/pegylated liposomal doxorubicin was generally well tolerated, with no farletuzumab-related grades 3-4 adverse events. The most commonly reported adverse events were associated with combination chemotherapy: fatigue (73.3%), nausea (46.7%), and neutropenia (40%). Ten patients had grade ≥3 adverse events, most frequently neutropenia and fatigue. No cardiac toxicity was seen. Best overall responses (RECIST) were a complete response for one patient, partial responses for 10 patients, and stable disease for four patients.
  
  
  CONCLUSIONS
  Farletuzumab plus carboplatin/pegylated liposomal doxorubicin in women with platinum-sensitive EOC demonstrated a safety profile consistent with that of carboplatin plus pegylated liposomal doxorubicin.
authors.affiliation: University of North Carolina Health Care, Division of Gynecology Oncology, Chapel Hill, NC, United States.
authors.forename: Kenneth H
authors.initials: KH
authors.lastname: Kim
authors.affiliation: Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD, United States.
authors.forename: Danijela
authors.initials: D
authors.lastname: Jelovac
authors.affiliation: Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD, United States.
authors.forename: Deborah K
authors.initials: DK
authors.lastname: Armstrong
authors.affiliation: Island Gynecologic Oncology, PLLC, Brightwaters, NY, United States.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Schwartz
authors.affiliation: Morphotek, Inc., Exton, PA, United States.
authors.forename: Susan C
authors.initials: SC
authors.lastname: Weil
authors.affiliation: Morphotek, Inc., Exton, PA, United States.
authors.forename: Charles
authors.initials: C
authors.lastname: Schweizer
authors.affiliation: University of Alabama at Birmingham, AL, United States. Electronic address: ralvarez@uabmc.edu.
authors.forename: Ronald D
authors.initials: RD
authors.lastname: Alvarez
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects*; D016190:Carboplatin / Q000008:administration & dosage / Q000009:adverse effects; D000077216:Carcinoma, Ovarian Epithelial; D004317:Doxorubicin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D005260:Female; D006801:Humans; D008875:Middle Aged; D009375:Neoplasms, Glandular and Epithelial / Q000188:drug therapy*; D010051:Ovarian Neoplasms / Q000188:drug therapy*; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000009:adverse effects
chemical_list: D061067:Antibodies, Monoclonal, Humanized; C506643:liposomal doxorubicin; C527484:farletuzumab; D011092:Polyethylene Glycols; D004317:Doxorubicin; D016190:Carboplatin
keywords: Farletuzumab; Monoclonal antibody therapy; Ovarian cancer; Pegylated liposomal doxorubicin; Platinum-sensitive relapse