Prospective validation of a prognostic score to improve patient selection for oncology phase I trials

J Clin Oncol. 2009 Jun 1;27(16):2692-6. doi: 10.1200/JCO.2008.19.5081. Epub 2009 Mar 30.

Abstract

Purpose: With the aim of improving patient selection for phase I trials, we previously performed a retrospective analysis of 212 phase I oncology patients where we were able to develop a prognostic score predicting overall survival (OS). This prospective study was performed to test the validity of the prognostic score.

Patients and methods: On the basis of our retrospective multivariate analysis, three factors were associated with poor survival (albumin < 35 g/L, lactate dehydrogenase [LDH] > upper limit of normal [ULN], and > two sites of metastases). We integrated these into a prognostic score ranging from 0 to 3 and analyzed this score in a prospectively selected cohort of 78 patients enrolled onto phase I trials.

Results: All patients had progressive disease before study entry. The median age was 56 years (range, 18 to 79 years). After a median follow-up time of 27.3 weeks, patients with a prognostic score of 0 to 1 (n = 43) had superior OS (33.0 weeks; 95% CI, 24 to 42 weeks) compared with patients with a score of 2 to 3 (n = 35; 15.7 weeks; 95% CI, 11 to 21 weeks). Our multivariate analysis confirmed that our prognostic score was an independent marker for OS, with a hazard ratio of 1.4 (95% CI, 1.02 to 1.9; P = .036).

Conclusion: This is the first prospective analysis confirming that a prognostic score based on objective markers, including albumin less than 35 g/L, LDH more than ULN, and more than two sites of metastasis, is a helpful tool in the process of patient selection for phase I trial entry.

Publication types

  • Research Support, Non-U.S. Gov't
  • Validation Study

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Biomarkers / blood
  • Clinical Trials, Phase I as Topic*
  • Disease-Free Survival
  • Female
  • Health Status Indicators*
  • Humans
  • Kaplan-Meier Estimate
  • L-Lactate Dehydrogenase / blood
  • Male
  • Middle Aged
  • Neoplasm Metastasis
  • Neoplasms / blood
  • Neoplasms / mortality
  • Neoplasms / pathology
  • Neoplasms / therapy*
  • Patient Selection*
  • Predictive Value of Tests
  • Proportional Hazards Models
  • Prospective Studies
  • Reproducibility of Results
  • Risk Assessment
  • Serum Albumin / analysis
  • Treatment Outcome
  • Young Adult

Substances

  • Biomarkers
  • Serum Albumin
  • L-Lactate Dehydrogenase