title: Anti-epidermal growth factor receptor monoclonal antibody cetuximab plus Doxorubicin in the treatment of metastatic castration-resistant prostate cancer.
abstract: OBJECTIVE
  An open-label, dose-escalating phase Ib/IIa trial was performed to establish a safety profile of ascending doses of cetuximab (IMC C225) in combination with doxorubicin administered weekly for 6 treatments in patients with metastatic castration-resistant prostate cancer. The secondary endpoint was to assess the efficacy of cetuximab in combination with doxorubicin as well as to determine the optimal biologic dose and the maximum tolerated dose.
  
  
  METHODS
  Patients in 8 groups received escalating doses of cetuximab 20-300 mg/m(2) plus doxorubicin 15 or 20 mg/m(2) given intravenously weekly for 6 consecutive weeks, followed by a 1-week observation period. A treatment response was defined as a > 50% decline in prostate-specific antigen (PSA) or regression of radiographically measurable disease.
  
  
  RESULTS
  Of the 36 treated patients, 25% had grade 2 neutropenia, 39% had leukopenia, and 44% had stomatitis at doxorubicin 20 mg/m(2). Erythematous skin exanthema was seen in 38% of the patients. There was no significant regression of bone or soft tissue disease, but stable disease was observed in 20 (65%) of the 31 patients with bone disease and 14 (61%) of the 23 patients with lymph node disease. Declines in PSA were modest in the 36 patients, with 1 (2.7%) with an 80% decline from baseline, 2 (5.6%) with > 50% to < 80% declines, and 14 (39%) with progression. Median survival was approximately 18 months.
  
  
  CONCLUSIONS
  In a heavily pretreated population of men with metastatic castration-resistant prostate cancer, this study of cetuximab/doxorubicin was associated with minimal PSA declines posttherapy, though median survival was longer compared to historical control groups. Further studies with cetuximab combined with more contemporary chemotherapy for castration-resistant prostate cancer might be warranted.
authors.affiliation: Genitourinary Oncology Service, Department of Medicine, Sidney Kimmel Center for Prostate and Urologic Cancers, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA. slovins@mskcc.org
authors.forename: Susan F
authors.initials: SF
authors.lastname: Slovin
authors.forename: W Kevin
authors.initials: WK
authors.lastname: Kelly
authors.forename: Andrew
authors.initials: A
authors.lastname: Wilton
authors.forename: Michael
authors.initials: M
authors.lastname: Kattan
authors.forename: Patricia
authors.initials: P
authors.lastname: Myskowski
authors.forename: John
authors.initials: J
authors.lastname: Mendelsohn
authors.forename: Howard I
authors.initials: HI
authors.lastname: Scher
mesh_terms: D000368:Aged; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000068818:Cetuximab; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D009919:Orchiectomy; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D004317:Doxorubicin; D017430:Prostate-Specific Antigen; D000068818:Cetuximab