title: Clinical Outcomes of Patients With Gastrointestinal Malignancies Participating in Phase I Clinical Trials.
abstract: Early-phase clinical trials play a pivotal role in drug development. However, limited data are available on outcomes of gastrointestinal (GI) cancer patients enrolled in phase I clinical trials. Here, we evaluated the characteristics associated with survival in GI cancer patients participating in phase I clinical trials and attempted to validate previously established prognostic models.
  
  
  
  All consecutive patients with advanced GI tumors who participated in phase I clinical trials at our institution from January 2007 to December 2013 and received at least 1 dose of the study drug were included. Cox regression models were used to estimate multivariable-adjusted hazard ratio (HR) and 95% confidence interval.
  
  
  
  In 243 study patients (median age, 62 y [range, 26 to 82 y]; 55% male), treatment included chemotherapy only (14%), targeted therapy (41%), chemotherapy+targeted therapy (42%), and others (2%) for the following disease types: pancreatic (42%), colorectal (34%), gastroesophageal (10%), hepatobiliary (13%), and others (2%). Response rate was 4%, with 38% achieving stable disease and 42% having progressive disease. Median survival was 5.8 months (range, 0.2 to 52.4 mo). Our multivariable Cox regression analyses included the following as predictors of survival: Eastern Cooperative Oncology Group performance score ≥1 (HR=1.76), prior systemic therapies ≥2 (HR=1.63), lactate dehydrogenase >618 IU/L (HR=1.85), sodium >135 mmol/L (HR=0.46), and white blood count >6×10/L (HR=1.5). Our data set was consistent with previous prognostic scores.
  
  
  
  This is the largest study to assess clinical outcomes in this patient population. Phase I trials provide clinical benefit to patients with advanced GI malignancies and should be recommended as a treatment option in appropriate patients.
authors.affiliation: Department of Internal Medicine, University of South Florida.
authors.forename: Aaron
authors.initials: A
authors.lastname: Denson
authors.affiliation: Clinical Research Unit.
authors.forename: Nancy
authors.initials: N
authors.lastname: Burke
authors.affiliation: Clinical Research Unit.
authors.forename: Georgine
authors.initials: G
authors.lastname: Wapinsky
authors.affiliation: Clinical Research Unit.
authors.forename: Barbara
authors.initials: B
authors.lastname: Bertels
authors.affiliation: Departments of Biostatistics and Bioinformatics.
authors.forename: Tzu-Hua
authors.initials: TH
authors.lastname: Juan
authors.affiliation: Departments of Biostatistics and Bioinformatics.
authors.forename: Jae
authors.initials: J
authors.lastname: Lee
authors.affiliation: Department of Gastrointestinal Oncology.
authors.forename: Gregory M
authors.initials: GM
authors.lastname: Springett
authors.affiliation: Department of Gastrointestinal Oncology.
authors.forename: Jonathan R
authors.initials: JR
authors.lastname: Strosberg
authors.affiliation: Department of Gastrointestinal Oncology.
authors.forename: Richard D
authors.initials: RD
authors.lastname: Kim
authors.affiliation: Chemical Biology and Molecular Medicine Program, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL.
authors.forename: Dan M
authors.initials: DM
authors.lastname: Sullivan
authors.affiliation: Department of Gastrointestinal Oncology.|Chemical Biology and Molecular Medicine Program, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL.
authors.forename: Amit
authors.initials: A
authors.lastname: Mahipal
mesh_terms: D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002173:Cancer Care Facilities; D002423:Cause of Death; D015331:Cohort Studies; D016001:Confidence Intervals; D018572:Disease-Free Survival; D005260:Female; D005431:Florida; D005770:Gastrointestinal Neoplasms / Q000188:drug therapy* / Q000401:mortality* / Q000473:pathology; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009361:Neoplasm Invasiveness / Q000473:pathology; D009367:Neoplasm Staging; D018579:Patient Selection; D011379:Prognosis; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D018570:Risk Assessment; D012737:Sex Factors; D016019:Survival Analysis; D016896:Treatment Outcome