title: Early mortality and overall survival in oncology phase I trial participants: can we improve patient selection?
abstract: BACKGROUND
  Patient selection for phase I trials (PIT) in oncology is challenging. A typical inclusion criterion for PIT is 'life expectancy > 3 months', however the 90 day mortality (90DM) and overall survival (OS) of patients with advanced solid malignancies are difficult to predict.
  
  
  METHODS
  We analyzed 233 patients who were enrolled in PIT at Princess Margaret Hospital. We assessed the relationship between 17 clinical characteristics and 90DM using univariate and multivariate logistic regression analyses to create a risk score (PMHI). We also applied the Royal Marsden Hospital risk score (RMI), which consists of 3 markers (albumin < 35g/L, > 2 metastatic sites, LDH > ULN).
  
  
  RESULTS
  Median age was 57 years (range 21-88). The 90DM rate was 14%; median OS was 320 days. Predictors of 90DM were albumin < 35g/L (OR = 8.2, p = 0.01), > 2 metastatic sites (OR = 2.6, p = 0.02), and ECOG > 0 (OR = 6.3, p = 0.001); all 3 factors constitute the PMHI. To predict 90DM, the PMHI performed better than the RMI (AUC = 0.78 vs 0.69). To predict OS, the RMI performed slightly better (RMI ≥ 2, HR = 2.2, p = 0.002 vs PMHI ≥ 2, HR = 1.6, p = 0.05).
  
  
  CONCLUSIONS
  To predict 90DM, the PMHI is helpful. To predict OS, risk models should include ECOG > 0, > 2 metastatic sites, and LDH > ULN. Prospective validation of the PMHI is warranted.
authors.affiliation: Division of Medical Oncology and Hematology, Princess Margaret Hospital, University of Toronto, Toronto, Canada.
authors.forename: Nicole G
authors.initials: NG
authors.lastname: Chau
authors.forename: Ana
authors.initials: A
authors.lastname: Florescu
authors.forename: Kelvin K
authors.initials: KK
authors.lastname: Chan
authors.forename: Lisa
authors.initials: L
authors.lastname: Wang
authors.forename: Eric X
authors.initials: EX
authors.lastname: Chen
authors.forename: Philippe
authors.initials: P
authors.lastname: Bedard
authors.forename: Amit M
authors.initials: AM
authors.lastname: Oza
authors.forename: Lillian L
authors.initials: LL
authors.lastname: Siu
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000378:metabolism; D017321:Clinical Trials, Phase I as Topic; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000175:diagnosis / Q000401:mortality* / Q000628:therapy; D018579:Patient Selection; D011379:Prognosis; D012189:Retrospective Studies; D016019:Survival Analysis; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D015415:Biomarkers