Multivariable analysis of prognostic factors for toxicity and survival for patients enrolled in phase I clinical trials

Ann Oncol. 2000 Feb;11(2):151-6. doi: 10.1023/a:1008368319526.

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.

Patients and 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.

Publication types

  • Meta-Analysis

MeSH terms

  • Adult
  • Age Distribution
  • Aged
  • Analysis of Variance
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / adverse effects*
  • Clinical Trials, Phase I as Topic*
  • Disease-Free Survival
  • Evaluation Studies as Topic
  • Female
  • Humans
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Neoplasms / diagnosis
  • Neoplasms / drug therapy*
  • Neoplasms / mortality*
  • Patient Selection
  • Prognosis
  • Proportional Hazards Models
  • Retrospective Studies
  • Risk Assessment
  • Sex Distribution
  • Survival Analysis

Substances

  • Antineoplastic Agents