title: Impact of geriatric risk factors on pegylated liposomal doxorubicin tolerance and efficacy in elderly metastatic breast cancer patients: final results of the DOGMES multicentre GINECO trial.
abstract: BACKGROUND
  Metastatic breast cancer chemotherapy in the elderly is considered effective in carefully selected patients, but there is little data regarding its effect in vulnerable patients.
  
  
  METHODS
  We evaluated tumour response (primary endpoint), feasibility and outcomes after six courses of an adapted dose of pegylated liposomal doxorubicin (PLD) (40 mg/m(2) every 28 days) as first-line chemotherapy for hormone-resistant MBC.
  
  
  RESULTS
  Of 60 patients >70 years (median 77 years), 15% had performance status ≥2 and 73% had visceral metastases. Geriatric assessment included: ≥2 comorbidities, 42%; ≥1 deficiency in Activities of Daily Living (ADL), 10% and Instrumental ADL (IADL), 82%; living in residential homes, 12%; albumin <35 g/L, 17%; body mass index (BMI) <21, 20%; depression, 17%; and lymphocytes ≤1 × 10(3)/mm(3), 27%. Complete response, partial response and stable disease were observed in 5%, 15% and 60%, respectively, but only 48% completed six cycles. Treatment discontinuations were mostly due to disease progression (18%) and non-haematological (NH) toxicities (22%). Eight patients died during treatment (three possibly related to PLD), and 15 had unplanned hospital admissions. Exploratory analyses to identify geriatric covariates associated with treatment outcomes revealed severe haematological toxicities significantly correlated with lymphocytes ≤1 × 10(3)/mm(3). NH toxicities correlated with age ≥80 years and living in residential homes. Progression-free survival (median 6.1 months) decreased with age, deficiency in IADL, cardiac dysfunction and living in residential homes. Overall survival (median 15.7 months) also decreased with living in residential homes.
  
  
  CONCLUSIONS
  Despite manageable haematological toxicities and expected response rates, PLD feasibility was poor in unselected elderly patients.
authors.affiliation: Department of Geriatric Medicine, Centre Hospitalier Lyon-Sud, Pierre Bénite, Université Lyon 1, Lyon, France. claire.falandry@chu-lyon.fr
authors.forename: C
authors.initials: C
authors.lastname: Falandry
authors.forename: E
authors.initials: E
authors.lastname: Brain
authors.forename: M
authors.initials: M
authors.lastname: Bonnefoy
authors.forename: F
authors.initials: F
authors.lastname: Mefti
authors.forename: N
authors.initials: N
authors.lastname: Jovenin
authors.forename: O
authors.initials: O
authors.lastname: Rigal
authors.forename: O
authors.initials: O
authors.lastname: Guillem
authors.forename: C
authors.initials: C
authors.lastname: El Kouri
authors.forename: L
authors.initials: L
authors.lastname: Uwer
authors.forename: S
authors.initials: S
authors.lastname: Abadie-Lacourtoisie
authors.forename: J
authors.initials: J
authors.lastname: Cretin
authors.forename: J P
authors.initials: JP
authors.lastname: Jacquin
authors.forename: D
authors.initials: D
authors.lastname: Paraiso
authors.forename: G
authors.initials: G
authors.lastname: Freyer
mesh_terms: D000203:Activities of Daily Living; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000556:secondary; D018572:Disease-Free Survival; D004317:Doxorubicin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D004334:Drug Administration Schedule; D005260:Female; D005602:France; D015577:Geriatric Assessment; D006331:Heart Diseases / Q000150:complications; D006707:Homes for the Aged; D006801:Humans; D053208:Kaplan-Meier Estimate; D015999:Multivariate Analysis; D009735:Nursing Homes; D016017:Odds Ratio; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D016016:Proportional Hazards Models; D018570:Risk Assessment; D012307:Risk Factors; D011795:Surveys and Questionnaires; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000903:Antibiotics, Antineoplastic; C506643:liposomal doxorubicin; D011092:Polyethylene Glycols; D004317:Doxorubicin
keywords: Geriatric/ageing; Liposomal pegylated doxorubicin; Metastatic breast cancer