title: Amongst eligible patients, age and comorbidity do not predict for dose-limiting toxicity from phase I chemotherapy.
abstract: BACKGROUND
  There are no clear predictors clinicians can use to determine who is more likely to experience dose-limiting toxicity (DLT) in phase I chemotherapy clinical trials. Many providers are reluctant to refer older adults to phase I trials because of concerns about the development of toxicity. The goal of this study was to identify clinical and nonclinical factors which were associated with the development of DLT in phase I studies.
  
  
  METHODS
  Patients (pts) were included if they were treated at maximally tolerated dose (MTD) and above. Studies were included only if MTD was reached. Data collected included age, comorbidity (Cumulative Illness Rating Score-Geriatrics), labs at enrollment, height, weight, performance status, cancer type, duration of diagnosis, prior treatment, drug level, smoking status, marital status, mean income, percent of population high school educated as determined by ZIP code, and distance to the phase I trial hospital. Those who did and did not have DLT were compared by bivariate and then multivariate analysis.
  
  
  RESULTS
  A total of 242 charts were reviewed from 24 cytotoxic chemotherapy studies, and 27 different types of cancer were represented. On bivariate analysis, mean age, household income (higher), weight, body surface area, dose of drug, alkaline phosphatase, hemoglobin, and LDH were significantly associated with DLT (P < 0.05). CIRS-G score was not associated with DLT. In multivariate analysis, dose level (P = 0.004) and distance from the phase I trial hospital (P = 0.04) were still significant predictors of DLT. Age did not predict for severity of DLT.
  
  
  CONCLUSIONS
  Age and comorbidity did not predict for development of DLT in phase I chemotherapy trials. Many of these pts were very fit, with relatively low CIRS-G scores, so the impact of comorbidity may not have been fully evaluated. Several social and clinical factors may predict for development of DLT. A prospective study is being planned to confirm these results.
authors: University of Wisconsin Paul P. Carbone Comprehensive Cancer Center, 600 Highland Ave, CSC K4/548, Madison, WI 53792, USA. ns3@medicine.wisc.edu
authors: Noelle K
authors: NK
authors: LoConte
authors: Maureen
authors: M
authors: Smith
authors: Dona
authors: D
authors: Alberti
authors: Jeffrey
authors: J
authors: Bozeman
authors: James F
authors: JF
authors: Cleary
authors: Ashley N
authors: AN
authors: Setala
authors: Geoff
authors: G
authors: Wodtke
authors: George
authors: G
authors: Wilding
authors: Kyle D
authors: KD
authors: Holen
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D017321:Clinical Trials, Phase I as Topic; D015897:Comorbidity; D064420:Drug-Related Side Effects and Adverse Reactions / Q000139:chemically induced / Q000175:diagnosis; D005260:Female; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009369:Neoplasms / Q000188:drug therapy* / Q000453:epidemiology; D011237:Predictive Value of Tests; D011379:Prognosis; D012189:Retrospective Studies
chemical_list: D000970:Antineoplastic Agents