TY - JOUR
T1 - Clinical Outcomes of Patients With Gastrointestinal Malignancies Participating in Phase I Clinical Trials
AU - Denson, Aaron
AU - Burke, Nancy
AU - Wapinsky, Georgine
AU - Bertels, Barbara
AU - Juan, Tzu Hua
AU - Lee, Jae
AU - Springett, Gregory M.
AU - Strosberg, Jonathan R.
AU - Kim, Richard D.
AU - Sullivan, Dan M.
AU - Mahipal, Amit
N1 - Publisher Copyright:
Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.
PY - 2018
Y1 - 2018
N2 - Objectives: 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. Materials and Methods: 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. Results: 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 ≥ (HR = 1.76), prior systemic therapies ≥ (HR = 1.63), lactate dehydrogenase >618 IU/L (HR = 1.85), sodium >135 mmol/L (HR = 0.46), and white blood count >6×109/L (HR = 1.5). Our data set was consistent with previous prognostic scores. Conclusions: 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.
AB - Objectives: 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. Materials and Methods: 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. Results: 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 ≥ (HR = 1.76), prior systemic therapies ≥ (HR = 1.63), lactate dehydrogenase >618 IU/L (HR = 1.85), sodium >135 mmol/L (HR = 0.46), and white blood count >6×109/L (HR = 1.5). Our data set was consistent with previous prognostic scores. Conclusions: 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.
KW - clinical trial
KW - clinical trial
KW - gastrointestinal neoplasms
KW - phase I
KW - survival
KW - therapeutics
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U2 - 10.1097/COC.0000000000000242
DO - 10.1097/COC.0000000000000242
M3 - Article
C2 - 26523441
AN - SCOPUS:84946085495
SN - 0277-3732
VL - 41
SP - 133
EP - 139
JO - American Journal of Clinical Oncology: Cancer Clinical Trials
JF - American Journal of Clinical Oncology: Cancer Clinical Trials
IS - 2
ER -