Michelle Treasure1, Barbara Daly2, Pingfu Fu3, Svetoslava Kerpedjieva4, Afshin Dowlati5, Neal J Meropol6,7. 1. Department of Medicine, Division of Hematology and Oncology, MetroHealth Medical Center, Case Western Reserve University, 2500 MetroHealth Drive, Cleveland, OH, 44109, USA. mxt269@case.edu. 2. Frances Payne Bolton School of Nursing, Case Western Reserve University, Cleveland, OH, USA. 3. Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, OH, USA. 4. Departments of Internal Medicine and Pediatrics, Hospital of the University of Pennsylvania, Philadelphia, PA, USA. 5. Department of Medicine, Division of Hematology and Oncology, University Hospitals Cleveland Medical Center, Case Western Reserve University, Cleveland, OH, USA. 6. University Hospitals Cleveland Medical Center, Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, OH, USA. 7. Flatiron Health, New York, NY, USA.
Abstract
PURPOSE: Phase I clinical trials are critical to development of cancer therapeutics. Adverse events (AEs) and symptom burden contribute to early treatment withdrawal, and it is often difficult to ascertain whether these events are disease- or treatment-related. Regardless, early withdrawal may delay determination of the effectiveness of potential new therapies. We sought to characterize the reasons for early treatment termination to identify potential modifiable events. METHODS: A retrospective chart review was conducted on solid tumor patients enrolled in institutional phase I clinical trials from 2003 to 2013 through the Case Comprehensive Cancer Center. RESULTS: Two hundred fifty-five patients were included in the analysis. The mean duration on study was 78.4 days (SD 63.4 days), and 23% of the patients were on study ≤ 30 days. Patients experienced an average of 25.1 AEs, of which 46.9% were non-laboratory. Constitutional symptoms (29.3%), gastrointestinal symptoms (24%), and pain (12.8%) were the most common non-laboratory AEs. Disease progression (57.6%) was the most common reason for study discontinuation, followed by adverse events (16.5%). Approximately 13% of the patients discontinued treatment for other reasons, of which 41.7% were identified as related to symptom burden on further review. Increased rates of AEs negatively correlated with duration on study (r = - 0.331; p < 0.01). CONCLUSIONS: AEs may lead to early termination of trial participation and confound clinical assessment of investigational treatments. Designing interventions to reduce AE burden may extend duration on trial, affect the recommended phase II dose, and benefit the quality of life of participants on phase I trials.
PURPOSE: Phase I clinical trials are critical to development of cancer therapeutics. Adverse events (AEs) and symptom burden contribute to early treatment withdrawal, and it is often difficult to ascertain whether these events are disease- or treatment-related. Regardless, early withdrawal may delay determination of the effectiveness of potential new therapies. We sought to characterize the reasons for early treatment termination to identify potential modifiable events. METHODS: A retrospective chart review was conducted on solid tumorpatients enrolled in institutional phase I clinical trials from 2003 to 2013 through the Case Comprehensive Cancer Center. RESULTS: Two hundred fifty-five patients were included in the analysis. The mean duration on study was 78.4 days (SD 63.4 days), and 23% of the patients were on study ≤ 30 days. Patients experienced an average of 25.1 AEs, of which 46.9% were non-laboratory. Constitutional symptoms (29.3%), gastrointestinal symptoms (24%), and pain (12.8%) were the most common non-laboratory AEs. Disease progression (57.6%) was the most common reason for study discontinuation, followed by adverse events (16.5%). Approximately 13% of the patients discontinued treatment for other reasons, of which 41.7% were identified as related to symptom burden on further review. Increased rates of AEs negatively correlated with duration on study (r = - 0.331; p < 0.01). CONCLUSIONS:AEs may lead to early termination of trial participation and confound clinical assessment of investigational treatments. Designing interventions to reduce AE burden may extend duration on trial, affect the recommended phase II dose, and benefit the quality of life of participants on phase I trials.
Entities:
Keywords:
Clinical trial; Palliative care; Phase I; drug-related side effects and adverse events; Quality of life; Retrospective studies
Authors: Elizabeth Horstmann; Mary S McCabe; Louise Grochow; Seiichiro Yamamoto; Larry Rubinstein; Troy Budd; Dale Shoemaker; Ezekiel J Emanuel; Christine Grady Journal: N Engl J Med Date: 2005-03-03 Impact factor: 91.245
Authors: Joseph Lipscomb; Bryce B Reeve; Steven B Clauser; Jeffrey S Abrams; Deborah Watkins Bruner; Laurie B Burke; Andrea M Denicoff; Patricia A Ganz; Kathleen Gondek; Lori M Minasian; Ann M O'Mara; Dennis A Revicki; Edwin P Rock; Julia H Rowland; Maria Sgambati; Edward L Trimble Journal: J Clin Oncol Date: 2007-11-10 Impact factor: 44.544
Authors: S Manne; D Kashy; T Albrecht; Y-N Wong; A Lederman Flamm; A B Benson; S M Miller; Linda Fleisher; J Buzaglo; N Roach; M Katz; E Ross; M Collins; D Poole; S Raivitch; D M Miller; T G Kinzy; T Liu; N J Meropol Journal: Eur J Cancer Care (Engl) Date: 2014-01-28 Impact factor: 2.520
Authors: Esmé Finlay; Hien L Lu; Hope R Henderson; Hope Henderson; Peter J O'Dwyer; David J Casarett Journal: Cancer Date: 2009-01-15 Impact factor: 6.860
Authors: R Berman; A Davies; T Cooksley; R Gralla; L Carter; E Darlington; F Scotté; C Higham Journal: Clin Oncol (R Coll Radiol) Date: 2020-08-16 Impact factor: 4.126