title: Phase I trial outcomes in older patients with advanced solid tumours.
abstract: BACKGROUND
  This study had two aims: (a) to test the hypothesis that advanced age is associated with lower levels of tolerability and clinical benefit to experimental Phase I trial agents; (b) to assess the validity of the Royal Marsden Hospital (RMH) prognostic score as a patient selection tool in older patients.
  
  
  METHODS
  Clinico-pathological characteristics and treatment outcomes of all patients treated consecutively from 2005 to 2009 in phase I trials at the RMH were recorded. All toxicity and clinical outcome data were compared between patients aged below and above 65 years of age.
  
  
  RESULTS
  One thousand and four patients were treated in 30 Phase I trials, with 315 (31%) patients aged 65 years and older. Grade 3-5 toxicities (22.8% vs 24.8% (P=0.52)), trial discontinuation (6% vs 4%; P=0.33), and dose interruptions (8.0% vs 8.0% (P=0.96)) were observed at similar rates in patients below and above 65 years of age, respectively. The overall response rate 5.2% vs 4.1%, progression-free survival (PFS) 1.9 vs 3.5 months and clinical benefit rate (CBR) at 6 months 15.2% vs 14.3% were comparable in both groups. To avoid bias due to the potential therapeutic benefit of abiraterone, comparisons were repeated excluding prostate cancer patients with similar results (ORR 4.6% vs 4%, PFS 1.8 vs 3.0 months, CBR at 6 months 13.5% vs 9.5%). Multivariate analysis indicated that the previously identified RMH score (including albumin and lactate dehydrogenase levels) was an accurate predictor of outcome.
  
  
  CONCLUSIONS
  Phase I clinical trials should be considered in patients with advanced cancers regardless of age, as older patients who enter these have similar safety and efficacy outcomes as their younger counterparts. The RMH prognostic score can assist in the selection of suitable older patients.
authors.affiliation: Drug Development Unit, The Royal Marsden NHS Foundation Trust, Sutton SM2 5PT, UK.|Gastrointestinal Cancers Unit, The Royal Marsden NHS Foundation Trust, Sutton SM2 5PT, UK.
authors.forename: K H
authors.initials: KH
authors.lastname: Khan
authors.affiliation: Drug Development Unit, The Royal Marsden NHS Foundation Trust, Sutton SM2 5PT, UK.|Division of Clinical Studies, The Institute of Cancer Research, Sutton SM2 5NG, UK.
authors.forename: T A
authors.initials: TA
authors.lastname: Yap
authors.affiliation: Breast Unit, The Royal Marsden NHS Foundation Trust, Sutton SM2 5PT, UK.
authors.forename: A
authors.initials: A
authors.lastname: Ring
authors.affiliation: Drug Development Unit, The Royal Marsden NHS Foundation Trust, Sutton SM2 5PT, UK.
authors.forename: L R
authors.initials: LR
authors.lastname: Molife
authors.affiliation: Drug Development Unit, The Royal Marsden NHS Foundation Trust, Sutton SM2 5PT, UK.
authors.forename: S
authors.initials: S
authors.lastname: Bodla
authors.affiliation: Drug Development Unit, The Royal Marsden NHS Foundation Trust, Sutton SM2 5PT, UK.
authors.forename: K
authors.initials: K
authors.lastname: Thomas
authors.affiliation: Drug Development Unit, The Royal Marsden NHS Foundation Trust, Sutton SM2 5PT, UK.
authors.forename: A
authors.initials: A
authors.lastname: Zivi
authors.affiliation: Drug Development Unit, The Royal Marsden NHS Foundation Trust, Sutton SM2 5PT, UK.
authors.forename: A
authors.initials: A
authors.lastname: Smith
authors.affiliation: Drug Development Unit, The Royal Marsden NHS Foundation Trust, Sutton SM2 5PT, UK.
authors.forename: I
authors.initials: I
authors.lastname: Judson
authors.affiliation: Drug Development Unit, The Royal Marsden NHS Foundation Trust, Sutton SM2 5PT, UK.|Division of Clinical Studies, The Institute of Cancer Research, Sutton SM2 5NG, UK.
authors.forename: U
authors.initials: U
authors.lastname: Banerji
authors.affiliation: Drug Development Unit, The Royal Marsden NHS Foundation Trust, Sutton SM2 5PT, UK.|Division of Clinical Studies, The Institute of Cancer Research, Sutton SM2 5NG, UK.
authors.forename: J S
authors.initials: JS
authors.lastname: de Bono
authors.affiliation: Drug Development Unit, The Royal Marsden NHS Foundation Trust, Sutton SM2 5PT, UK.|Division of Clinical Studies, The Institute of Cancer Research, Sutton SM2 5NG, UK.
authors.forename: S B
authors.initials: SB
authors.lastname: Kaye
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects* / Q000627:therapeutic use; D017321:Clinical Trials, Phase I as Topic; D015331:Cohort Studies; D015897:Comorbidity; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009369:Neoplasms / Q000188:drug therapy* / Q000453:epidemiology / Q000473:pathology; D011379:Prognosis; D012189:Retrospective Studies; D016896:Treatment Outcome; D047368:Tumor Burden; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents