title: A phase II trial with anti-Lewis-Y monoclonal antibody (hu3S193) for the treatment of platinum resistant/refractory ovarian, fallopian tube and primary peritoneal carcinoma.
abstract: OBJECTIVE
  The primary objective was to evaluate the clinical efficacy of hu3S193, a humanized monoclonal antibody against the Lewis-Y antigen, in patients with platinum resistant/refractory ovarian, fallopian tube and primary peritoneal carcinoma. Secondary objectives were safety and pharmacokinetics. In addition, we sought to determine the potential interaction of clinical benefit and patient characteristics.
  
  
  METHODS
  This two-stage, multicenter, single arm, phase II trial enrolled eligible patients to receive hu3S193 weekly at a dose of 20mg/m(2) intravenously for 8 weeks (1 cycle) to a maximum of 3 cycles. Efficacy was measured as clinical benefit rate (objective response or stable disease for at least 24 weeks).
  
  
  RESULTS
  26 of 31 patients were eligible for efficacy analysis. No complete/partial responses were observed. Six patients had stable disease for 24+weeks [clinical benefit rate 23% (95% CI=9.77%-46.71%)]. Median PFS was 8.4 weeks (95% CI=6.0 to 16.1). Median PFS differed between patients with no ascites and no visceral disease and patients with ascites and/or visceral disease [16.1 vs. 8.1 weeks (p=0.0058)]. The most commonly reported treatment-related adverse events were fatigue (19.3%) and nausea (16.2%). Allergic reactions occurred in 6 patients (5 with Grade 1/2; 1 with Grade 3).
  
  
  CONCLUSIONS
  Hu3S193 lacked sufficient activity in the first stage of the study to open enrollment to the second stage. However, based on the longer PFS in patients with no ascites and no visceral disease, consolidation strategies in platinum sensitive disease are currently being tested.
authors.affiliation: Hospital Israelita Albert Einstein, Avenida Albert Einstein, 627, São Paulo, SP 05651-901, Brazil. Electronic address: osmaletz@einstein.br.
authors.forename: Oren
authors.initials: O
authors.lastname: Smaletz
authors.affiliation: Instituto do Câncer do Estado de São Paulo - University of São Paulo School of Medicine. Avenida Doutor Arnaldo, 251, São Paulo, SP 01255-000, Brazil.
authors.forename: Maria D P E
authors.initials: MD
authors.lastname: Diz
authors.affiliation: Instituto Nacional do Câncer José Alencar Gomes da Silva, Praça Cruz Vermelha, 23, Rio de Janeiro, RJ 20230-130, Brazil.
authors.forename: Claudio C
authors.initials: CC
authors.lastname: do Carmo
authors.affiliation: Hospital Alemão Oswaldo Cruz, Rua João Julião, 331, São Paulo, SP 01323-903, Brazil.
authors.forename: Jorge
authors.initials: J
authors.lastname: Sabbaga
authors.affiliation: Hospital da Baleia, Rua Juramento, 1464, Belo Horizonte, MG 30285-000, Brazil.
authors.forename: Geraldo F
authors.initials: GF
authors.lastname: Cunha-Junior
authors.affiliation: Hospital de Clinicas de Porto Alegre, Rua Ramiro Barcelos, 2350, Porto Alegre, RS 90035-903, Brazil.
authors.forename: Sergio J
authors.initials: SJ
authors.lastname: Azevedo
authors.affiliation: Hospital Sírio-Libanês, Rua Dona Adma Jafet, 91, São Paulo, SP 01308-050, Brazil.
authors.forename: Fernando C
authors.initials: FC
authors.lastname: Maluf
authors.affiliation: Pontifícia Universidade Católica do Rio Grande do Sul School of Medicine, Rua Padre Chagas 66, 203, Porto Alegre, RS 90570-080, Brazil.
authors.forename: Carlos H
authors.initials: CH
authors.lastname: Barrios
authors.affiliation: Instituto Brasileiro de Controle do Câncer, Av. Alcântara Machado, 2576, São Paulo, SP 03102-002, Brazil.
authors.forename: Ronaldo L
authors.initials: RL
authors.lastname: Costa
authors.affiliation: Recepta Biopharma, Rua Tabapuã, 1123, São Paulo, SP 04533-014, Brazil.
authors.forename: Ana G
authors.initials: AG
authors.lastname: Fontana
authors.affiliation: Recepta Biopharma, Rua Tabapuã, 1123, São Paulo, SP 04533-014, Brazil.
authors.forename: Vivian
authors.initials: V
authors.lastname: Madrigal
authors.affiliation: Biocâncer Centro de Pesquisa Clínica SA, Avenida Bernardo Monteiro, 890, Belo Horizonte, MG 30150-281, Brazil.
authors.forename: Alberto J
authors.initials: AJ
authors.lastname: Wainstein
authors.affiliation: Biocâncer Centro de Pesquisa Clínica SA, Avenida Bernardo Monteiro, 890, Belo Horizonte, MG 30150-281, Brazil.
authors.forename: Fernanda P
authors.initials: FP
authors.lastname: Yeda
authors.affiliation: Department of Pathology, University of São Paulo School of Medicine, Av. Dr. Arnaldo, 455, São Paulo, SP 01246-903, Brazil.
authors.forename: Venâncio A
authors.initials: VA
authors.lastname: Alves
authors.affiliation: Laboratório Biofármacos em Células Animais, Instituto Butantan, Av. Vital Brasil, 1500, São Paulo, SP 05503-900, Brazil.
authors.forename: Ana M
authors.initials: AM
authors.lastname: Moro
authors.affiliation: DASA Group, Av. Juruá, 434, Barueri, SP 06455-010, Brazil.
authors.forename: Roberto
authors.initials: R
authors.lastname: Blasbalg
authors.affiliation: Ludwig Institute for Cancer Research, Olivia Newton-John Cancer Research Institute, and La Trobe University, Melbourne 3084, Australia.
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Scott
authors.affiliation: Ludwig Institute for Cancer Research, Olivia Newton-John Cancer Research Institute, and La Trobe University, Melbourne 3084, Australia.
authors.forename: Eric W
authors.initials: EW
authors.lastname: Hoffman
mesh_terms: D000328:Adult; D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage* / Q000009:adverse effects / Q000276:immunology / Q000493:pharmacokinetics; D000077216:Carcinoma, Ovarian Epithelial; D018572:Disease-Free Survival; D019008:Drug Resistance, Neoplasm; D005185:Fallopian Tube Neoplasms / Q000276:immunology / Q000378:metabolism / Q000628:therapy*; D005260:Female; D006801:Humans; D007983:Lewis Blood Group Antigens / Q000276:immunology; D008875:Middle Aged; D009375:Neoplasms, Glandular and Epithelial / Q000276:immunology / Q000378:metabolism / Q000628:therapy*; D009944:Organoplatinum Compounds / Q000494:pharmacology; D010051:Ovarian Neoplasms / Q000276:immunology / Q000378:metabolism / Q000628:therapy*; D010534:Peritoneal Neoplasms / Q000276:immunology / Q000378:metabolism / Q000628:therapy*; D055815:Young Adult
chemical_list: D061067:Antibodies, Monoclonal, Humanized; C522039:Hu3S193 monoclonal antibody; D007983:Lewis Blood Group Antigens; C094162:Lewis Y antigen; D009944:Organoplatinum Compounds
keywords: Anti Lewis-Y monoclonal antibody (hu3S193); platinum resistant/refractory ovarian cancer