Relationship between phase I study duration and symptom burden
- 161 Downloads
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.
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.
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).
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.
KeywordsClinical trial Phase I; drug-related side effects and adverse events Retrospective studies Quality of life Palliative care
Funding and support
This study was supported by the Case Comprehensive Cancer Center, grant NCI P30.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
- 2.Manne S, Kashy D, Albrecht T et al (2014) Attitudinal barriers to participation in oncology clinical trials: factor analysis and correlates of barriers. Eur J Cancer Care (Engl). https://doi.org/10.1111/ecc.12180
- 3.Basch E, Iasonos A, McDonough T et al (2006) Patient versus clinician symptom reporting using the National Cancer Institute Common Terminology Criteria for Adverse Events: results of a questionnaire-based study. Lancet Oncol 7(11):903–909. https://doi.org/10.1016/S1470-2045(06)70910-X CrossRefPubMedGoogle Scholar
- 4.Sneeuw KCA, Sprangers MAG, Aaronson NK (2002) The role of health care providers and significant others in evaluating the quality of life of patients with chronic disease. J Clin Epidemiol 55(11):1130–1143 http://www.ncbi.nlm.nih.gov/pubmed/12507678. Accessed August 14, 2016CrossRefPubMedGoogle Scholar
- 9.Kroenke K, Zhong X, Theobald D, Wu J, Tu W, Carpenter JS (2010) Somatic symptoms in patients with cancer experiencing pain or depression: prevalence, disability, and health care use. Arch Intern Med 170(18):1686–1694. https://doi.org/10.1001/archinternmed.2010.337 CrossRefPubMedPubMedCentralGoogle Scholar
- 13.Movsas B, Moughan J, Sarna L et al (2009) Quality of life supersedes the classic prognosticators for long-term survival in locally advanced non-small-cell lung cancer: an analysis of RTOG 9801. J Clin Oncol 27(34):5816–5822. https://doi.org/10.1200/JCO.2009.23.7420 CrossRefPubMedPubMedCentralGoogle Scholar
- 14.Bruner DW, Bryan CJ, Aaronson N et al (2007) Issues and challenges with integrating patient-reported outcomes in clinical trials supported by the National Cancer Institute-sponsored clinical trials networks. J Clin Oncol 25(32):5051–5057. https://doi.org/10.1200/JCO.2007.11.3324 CrossRefPubMedPubMedCentralGoogle Scholar
- 17.Sneeuw KC, Aaronson NK, Sprangers MA, Detmar SB, Wever LD, Schornagel JH (1998) Comparison of patient and proxy EORTC QLQ-C30 ratings in assessing the quality of life of cancer patients. J Clin Epidemiol 51(7):617–631 http://www.ncbi.nlm.nih.gov/pubmed/9674669. Accessed August 14, 2016CrossRefPubMedGoogle Scholar