Supportive Care in Cancer

, Volume 26, Issue 3, pp 731–737 | Cite as

Relationship between phase I study duration and symptom burden

  • Michelle TreasureEmail author
  • Barbara Daly
  • Pingfu Fu
  • Svetoslava Kerpedjieva
  • Afshin Dowlati
  • Neal J. Meropol
Original Article



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.


Clinical 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.


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Copyright information

© Springer-Verlag GmbH Germany 2017

Authors and Affiliations

  • Michelle Treasure
    • 1
    Email author
  • Barbara Daly
    • 2
  • Pingfu Fu
    • 3
  • Svetoslava Kerpedjieva
    • 4
  • Afshin Dowlati
    • 5
  • Neal J. Meropol
    • 6
    • 7
  1. 1.Department of Medicine, Division of Hematology and Oncology, MetroHealth Medical CenterCase Western Reserve UniversityClevelandUSA
  2. 2.Frances Payne Bolton School of NursingCase Western Reserve UniversityClevelandUSA
  3. 3.Department of Epidemiology and BiostatisticsCase Western Reserve UniversityClevelandUSA
  4. 4.Departments of Internal Medicine and PediatricsHospital of the University of PennsylvaniaPhiladelphiaUSA
  5. 5.Department of Medicine, Division of Hematology and Oncology, University Hospitals Cleveland Medical CenterCase Western Reserve UniversityClevelandUSA
  6. 6.University Hospitals Cleveland Medical Center, Case Comprehensive Cancer CenterCase Western Reserve UniversityClevelandUSA
  7. 7.Flatiron HealthNew YorkUSA

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