90-Days mortality rate in patients treated within the context of a phase-I trial: How should we identify patients who should not go on trial?

Background: The primary objectives of phase-I trials include the definition of drug toxicities and the recommendation of phase-II doses. in order to safeguard the well-being of its participants, a common inclusion criterion is that of life expectancy > 3 months. However, previous studies have shown that about 20% of these patients do not survive beyond this time-point. Methods: We identified 97 patients who died within the first 90 days of treatment out of a total of 654 consecutively treated phase-I patients, from June 2003 to June 2007. This cohort was compared to a control group comprising 215 patients who lived > 90 days on phase-I studies and were treated from January 2005 to June 2006. Results: In keeping with our recently reported phase-I survival risk score, multivariate analysis demonstrated that patients who died within the first 90 days had lower albumin (p = 0.010), greater number of metastatic sites (p = 0.00001) and higher frequency of elevated LDH (p = 0.0002). This analysis also showed that 86% of patients who died during the first 90 days had an increased risk score of 2/3 compared to 39% in the control group. Furthermore, three additional factors were identified, namely younger age (p = 0.024), higher white cell count (p = 0.028) and poorer ECOG PS (p = 0.012) but the addition of these did not improve the ability to predict 90-day mortality compared to the afore-mentioned risk score. Conclusions: There is good evidence that our easily derivable scoring system provides an objective method to identify patients with a very limited life expectancy in whom participation in phase-I trials should be carefully evaluated. (C) 2008 Elsevier Ltd. All rights reserved.