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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?

2008; Elsevier BV; Volume: 44; Issue: 11 Linguagem: Inglês

10.1016/j.ejca.2008.04.017

1879-0852

Hendrik‐Tobias Arkenau, David Olmos, Joo Ern Ang, Jorge Barriuso, Vasilios Karavasilis, S. Ashley, Johann S. de Bono, Ian Judson, Stan B. Kaye,

Ethics in Clinical Research

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.