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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

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.

Keywords

Clinical trial Phase I; drug-related side effects and adverse events Retrospective studies Quality of life Palliative care 

Notes

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.

References

  1. 1.
    Cheng JD, Hitt J, Koczwara B, Schulman KA et al (2000) Impact of quality of life on patient expectations regarding phase I clinical trials. J Clin Oncol 18(2):421–428 http://www.ncbi.nlm.nih.gov/pubmed/10637258 CrossRefPubMedGoogle Scholar
  2. 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. 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. 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
  5. 5.
    Finlay E, Lu HL, Henderson H, O’Dwyer PJ, Casarett DJ (2009) Do phase 1 patients have greater needs for palliative care compared with other cancer patients? Cancer 115(2):446–453.  https://doi.org/10.1002/cncr.24025 CrossRefPubMedGoogle Scholar
  6. 6.
    Healy JM, Patel T, Lee S, Sanchez-Reilly S (2011) Do symptoms matter when considering patients for phase I clinical trials?: a pilot study of older adults with advanced cancer. Am J Hosp Palliat Care 28(7):463–466.  https://doi.org/10.1177/1049909111400723 CrossRefPubMedGoogle Scholar
  7. 7.
    Hyman DM, Eaton AA, Gounder MM et al (2014) Nomogram to predict cycle-one serious drug-related toxicity in phase I oncology trials. J Clin Oncol 32(6):519–526.  https://doi.org/10.1200/JCO.2013.49.8808 CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Martinez KA, Snyder CF, Malin JL, Dy SM (2014) Is race/ethnicity related to the presence or severity of pain in colorectal and lung cancer? J Pain Symptom Manag 48(6):1050–1059.  https://doi.org/10.1016/j.jpainsymman.2014.02.005 CrossRefGoogle Scholar
  9. 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
  10. 10.
    Basch E, Deal AM, Kris MG et al (2016) Symptom monitoring with patient-reported outcomes during routine cancer treatment: a randomized controlled trial. J Clin Oncol 34(6):557–565.  https://doi.org/10.1200/JCO.2015.63.0830 CrossRefPubMedGoogle Scholar
  11. 11.
    Lipscomb J, Reeve BB, Clauser SB et al (2007) Patient-reported outcomes assessment in cancer trials: taking stock, moving forward. J Clin Oncol 25(32):5133–5140.  https://doi.org/10.1200/JCO.2007.12.4644 CrossRefPubMedGoogle Scholar
  12. 12.
    Gotay CC, Kawamoto CT, Bottomley A, Efficace F (2008) The prognostic significance of patient-reported outcomes in cancer clinical trials. J Clin Oncol 26(8):1355–1363.  https://doi.org/10.1200/JCO.2007.13.3439 CrossRefPubMedGoogle Scholar
  13. 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. 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
  15. 15.
    Horstmann E, McCabe MS, Grochow L et al (2005) Risks and benefits of phase 1 oncology trials, 1991 through 2002. N Engl J Med 352(9):895–904.  https://doi.org/10.1056/NEJMsa042220 CrossRefPubMedGoogle Scholar
  16. 16.
    Cleeland CS (2007) Symptom burden: multiple symptoms and their impact as patient-reported outcomes. J Natl Cancer Inst Monogr 37:16–21.  https://doi.org/10.1093/jncimonographs/lgm005 CrossRefGoogle Scholar
  17. 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

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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