title: Family history of cancer rather than p53 status predicts efficacy of pegylated liposomal doxorubicin and oxaliplatin in relapsed ovarian cancer.
abstract: BACKGROUND
  The aim of the study was to assess the efficacy of pegylated liposomal doxorubicin (PLD) and oxaliplatin in patients affected by relapsed epithelial ovarian cancer with a family history of BRCA and p53 mutations.
  
  
  METHODS
  Seventy-two women received a median of 7.5 courses of PLD at 30 to 35 mg/m2 plus oxaliplatin at 70 mg/m2, and associations between BRCA1/2 and TP53 status and overall survival (OS) were determined. Thirty-eight had a short platinum-free interval (PFI; <12 months), and 34 had a long PFI (> or =12 months).
  
  
  RESULTS
  Nine patients had BRCA1 mutations, and 1 had a BRCA2 mutation. Platinum sensitivity was associated with OS (P = 0.0001). At a median follow-up of 9.3 months, objective response rate, median time to progression, and OS were 47.3%, 5.8 months, and 12.9 months, respectively, in short PFI compared with the 76.5%, 11.5 months, and 47.7 months in long PFI. p53 status did not correlate to these parameters. The median time to progression was 11.5 months for high-risk patients versus 6.5 months for patients with sporadic cancer (P = 0.0188), and the median OS from the start of treatment was 48.7 and 16.2 months (P = 0.0032), respectively. Toxicity was mostly grade 1 or 2.
  
  
  CONCLUSIONS
  High response rates in the long-PFI patients indicate that this treatment is beneficial and well tolerated. Platinum sensitivity and positive family history and/or a BRCA1/BRCA2 mutation are a useful predictor of response.
authors.affiliation: Istituto Oncologico Veneto-IRCCS, Department of Pathology, University of Padova, via Gattamelata 64, Padova, Italy. mariaorn@libero.it
authors.forename: Maria Ornella
authors.initials: MO
authors.lastname: Nicoletto
authors.forename: Roberta
authors.initials: R
authors.lastname: Bertorelle
authors.forename: Lucia
authors.initials: L
authors.lastname: Borgato
authors.forename: Gian Luca
authors.initials: GL
authors.lastname: De Salvo
authors.forename: Grazia
authors.initials: G
authors.lastname: Artioli
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Lombardi
authors.forename: Fable
authors.initials: F
authors.lastname: Zustovich
authors.forename: Raffaella
authors.initials: R
authors.lastname: Marcato
authors.forename: Anna
authors.initials: A
authors.lastname: Parenti
authors.forename: Marco
authors.initials: M
authors.lastname: Montagna
authors.forename: Martin E
authors.initials: ME
authors.lastname: Donach
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002277:Carcinoma / Q000175:diagnosis* / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality; D004317:Doxorubicin / Q000008:administration & dosage / Q000031:analogs & derivatives; D005192:Family Health; D005260:Female; D019398:Genes, BRCA1 / Q000502:physiology; D024522:Genes, BRCA2 / Q000502:physiology; D016158:Genes, p53 / Q000502:physiology; D006801:Humans; D008875:Middle Aged; D009154:Mutation / Q000502:physiology; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D010051:Ovarian Neoplasms / Q000175:diagnosis* / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality; D000077150:Oxaliplatin; D011092:Polyethylene Glycols / Q000008:administration & dosage; D011379:Prognosis; D012008:Recurrence; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D009944:Organoplatinum Compounds; C506643:liposomal doxorubicin; D000077150:Oxaliplatin; D011092:Polyethylene Glycols; D004317:Doxorubicin