title: Do elderly patients benefit from enrollment into Phase I Trials?
abstract: BACKGROUND
  Despite the significant burden of cancer in the older population, their outcomes in the context of phase I studies have been poorly studied. While the Royal Marsden Hospital (RMH) prognostic score (albumin, lactate dehydrogenase [LDH], number of metastatic sites) is validated in this setting, its utility among the elderly is uncertain.
  
  
  METHODS
  A total of 296 consecutive patients who were treated in 20 phase I trials from 2005 to 2012 in our unit were analysed. Clinical characteristics and outcomes between young (<65, n=202) and older patients (≥65, n=94) were compared.
  
  
  RESULTS
  The median age of the older patients was 69 years (65-84) and 71% were males. Although elderly patients had more co-morbidities and lower albumin levels at baseline, there was no significant difference in survival (8.8 months versus 9.9 months, p=0.68) and clinical benefit rate (69% versus 56%, p=0.07) compared to younger patients after median follow-up of 7.1 months (0.36-50.6 months). Age (p=0.23) did not have any bearing on occurrence of grade 3/4 toxicities. Twenty-six percent of elderly patients experienced grade 3/4 toxicities. The prognostic factors for overall survival (OS) identified in multivariate analysis were prior lines of chemotherapy (0-2 versus ≥3), baseline sodium levels (≥135 versus <135 mmol/L) and platelet levels (≤400 versus >400×10(9)). We developed a risk nomogram based on the factors prognostic of survival with concordance index of 0.65. The RMH model yielded a concordance index of 0.635.
  
  
  CONCLUSIONS
  Elderly patients enrolled into phase I clinical trials had similar survival outcomes and toxicity profiles compared to younger patients. Risk scoring models to aid patient selection need further clarification.
authors.affiliation: Department of Medical Oncology, National Cancer Centre, Singapore.
authors.forename: Wai Meng
authors.initials: WM
authors.lastname: Tai
authors.affiliation: Clinical Trials & Epidemiological Sciences National Cancer Centre, Singapore.
authors.forename: Cindy
authors.initials: C
authors.lastname: Lim
authors.affiliation: Department of Medical Oncology, National Cancer Centre, Singapore.
authors.forename: Aziah
authors.initials: A
authors.lastname: Ahmad
authors.affiliation: Clinical Trials & Epidemiological Sciences National Cancer Centre, Singapore.
authors.forename: Whee Sze
authors.initials: WS
authors.lastname: Ong
authors.affiliation: Department of Medical Oncology, National Cancer Centre, Singapore.
authors.forename: Su Pin
authors.initials: SP
authors.lastname: Choo
authors.affiliation: Department of Medical Oncology, National Cancer Centre, Singapore.
authors.forename: Wan Teck
authors.initials: WT
authors.lastname: Lim
authors.affiliation: Department of Medical Oncology, National Cancer Centre, Singapore.
authors.forename: Eng Huat
authors.initials: EH
authors.lastname: Tan
authors.affiliation: Department of Medical Oncology, National Cancer Centre, Singapore.
authors.forename: Ravindran
authors.initials: R
authors.lastname: Kanesvaran
authors.affiliation: Department of Medical Oncology, National Cancer Centre, Singapore.
authors.forename: Daniel Shao Weng
authors.initials: DS
authors.lastname: Tan
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000378:metabolism; D017321:Clinical Trials, Phase I as Topic / Q000706:statistics & numerical data*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000401:mortality*; D012189:Retrospective Studies; D018570:Risk Assessment; D016019:Survival Analysis; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D015415:Biomarkers
keywords: Elderly; Oncology clinical trials; Phase I