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.
Arkenau
Hendrik-Tobias
HT
Drug Development Unit, Royal Marsden Hospital and Institute of Cancer Research, Downs Road, SM2 5PT Sutton, United Kingdom. hendrik-tobias.arkenau@icr.ac.uk
Olmos
David
D
Ang
Joo Ern
JE
Barriuso
Jorge
J
Karavasilis
Vasilios
V
Ashley
Sue
S
de Bono
Johann
J
Judson
Ian
I
Kaye
Stan
S
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D017321:Clinical Trials, Phase I as Topic / Q000401:mortality*; D015331:Cohort Studies; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000401:mortality*; D018579:Patient Selection; D011379:Prognosis; D012189:Retrospective Studies; D012307:Risk Factors; D016019:Survival Analysis