title: Multivariable analysis of prognostic factors for toxicity and survival for patients enrolled in phase I clinical trials.
abstract: BACKGROUND
  Patients with advanced solid tumors may be included in phase I clinical trials. In such studies, the benefit expected is generally lower than the likelihood of toxicity and may even be non-existent if the patient's life expectancy is too short. This study was performed to identify prognostic variables for toxicity and survival in patients who participate in phase I clinical trials.
  
  
  METHODS
  One hundred fifty-four patients treated on a phase I clinical trial in our institute were evaluated retrospectively. Univariable and multivariable analyses of patients' characteristics were undertaken to determine their effects on the probability of grade 3 and 4 toxicity and on survival.
  
  
  RESULTS
  Grade 3 or 4 toxicity was experienced by 56 patients (36%): dosage level at entry (P < 0.001) and age over 65 years (P = 0.03) were independently associated with the risk of toxicity. Median overall survival was 5 months. The multivariable analysis identified performance status 2 or 3 (P < 0.001) and lactate dehydrogenase levels greater than 600 UI (P < 0.001) as independent adverse prognostic variables for overall survival. Using these two parameters, we determined a prognostic index which allowed us to discriminate three risk groups of patients with an observed median survival of 8.5, 4.5 and 1.5 months, respectively.
  
  
  CONCLUSIONS
  Subgroups with different survival expectancy can be identified among patients who are eligible for phase I clinical trials. If confirmed, the proposed prognostic model may be useful for therapeutic decision making in palliative oncology.
authors.affiliation: Département de Cancérologie Médicale, Centre Léon Bérard, Lyon, France. bachelot@lyon.fnclcc.fr
authors.forename: T
authors.initials: T
authors.lastname: Bachelot
authors.forename: I
authors.initials: I
authors.lastname: Ray-Coquard
authors.forename: G
authors.initials: G
authors.lastname: Catimel
authors.forename: C
authors.initials: C
authors.lastname: Ardiet
authors.forename: J P
authors.initials: JP
authors.lastname: Guastalla
authors.forename: A
authors.initials: A
authors.lastname: Dumortier
authors.forename: F
authors.initials: F
authors.lastname: Chauvin
authors.forename: J P
authors.initials: JP
authors.lastname: Droz
authors.forename: T
authors.initials: T
authors.lastname: Philip
authors.forename: M
authors.initials: M
authors.lastname: Clavel
mesh_terms: D000328:Adult; D017677:Age Distribution; D000368:Aged; D000704:Analysis of Variance; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects*; D017321:Clinical Trials, Phase I as Topic; D018572:Disease-Free Survival; D005069:Evaluation Studies as Topic; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009369:Neoplasms / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality*; D018579:Patient Selection; D011379:Prognosis; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D018570:Risk Assessment; D017678:Sex Distribution; D016019:Survival Analysis
chemical_list: D000970:Antineoplastic Agents