Skip to main content
SpringerLink
Log in

Research Methods: Clinical Trials in Geriatric Oncology

  • Reference work entry
  • First Online:
Geriatric Oncology

Abstract

For various reasons, older adults are underrepresented in cancer clinical trials. As the selection criteria in randomized controlled trials are well controlled, younger and fitter patients are usually only eligible, making it difficult for clinicians to draw conclusions on the effects of drugs in older, frail, or unfit adults. With an aging world population, more attention needs to be focused on geriatric oncology, but the challenge lies in designing trials that capture the heterogeneity of an entire population, particularly the elderly and frail.

Separate trials for older patients are needed that incorporate more appropriate end points and suitable control arms. Pharmacokinetic studies should also be undertaken given the effect of aging organs on drug pharmacokinetics. How to design such trials in the absence of global standardized geriatric assessment tools and definitions is, however, challenging.

Randomized or single-arm phase II trials in older adults can provide important information on efficacy and toxicity where a phase III randomized controlled trial (RCT) is not feasible. Observational cohort studies are proposed as an adjunct to RCTs. Large and well-designed observational cohort studies can capture relevant and clinically meaningful data in real-world settings on older patients ineligible for RCTs.

Better clinical trial design is crucial to understanding the impact of new cancer therapies on older patients. Trials in older cancer patients should be compulsory.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 699.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD 999.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Similar content being viewed by others

References

  • Audisio RA, Pope D, Ramesh HS, et al. Shall we operate? Preoperative assessment in elderly cancer patients (PACE) can help – a SIOG surgical task force prospective study. Crit Rev Oncol Hematol. 2008;65:156–63.

    Article  CAS  Google Scholar 

  • Bottomley A, Vanvoorden V, Flechtner H, et al. The challenges and achievements involved in implementing quality of life research in cancer clinical trials. Eur J Cancer. 2003;39:275–85.

    Article  CAS  Google Scholar 

  • Cerreta F, Ankri J, Bowen D, et al. Baseline frailty evaluation in drug development. J Frailty Aging. 2016;5(3):139–40. https://doi.org/10.14283/jfa.2016.99.

    Article  CAS  PubMed  Google Scholar 

  • Cole BF, Gelber RD, Goldhirsch A. Cox regression models for quality adjusted survival analysis. Stat Med. 1993;12(10):975–87.

    Article  CAS  Google Scholar 

  • Derks MGM, Portielje JEA, Liefers GJ, et al. Variation in survival in older women with non-metastatic breast cancer in Europe: a population based study from the EURECCA Breast Cancer Group (2017).

    Google Scholar 

  • Escudier B, Eisen T, Stadler WM, et al. Sorafenib in advanced clear-cell renal-cell carcinoma. N Engl J Med. 2007;356(2):125–34.

    Article  CAS  Google Scholar 

  • Glasziou PP, Simes RJ, Gelber RD. Quality adjusted survival analysis. Stat Med. 1990;9(11):1259–76.

    Article  CAS  Google Scholar 

  • Hurria A, Dale W, Mooney M, et al. Designing therapeutic clinical trials for older and frail adults with cancer: U13 conference recommendations. J Clin Oncol. 2014;32:2587–94.

    Article  Google Scholar 

  • Hurria A, Levit L, Dale W, et al. Improving the evidence base for treating older adults with cancer: American Society of Clinical Oncology statement. J Clin Oncol. 2015;33:3826–33.

    Article  Google Scholar 

  • Kennedy BJ. Aging and cancer. J Clin Oncol. 1998;6:1903–11.

    Article  Google Scholar 

  • Kleist P. Composite endpoints: proceed with caution. Appl Clin Trials. 2016;15:50–7.

    Google Scholar 

  • Lange M, Heutte N, Rigal O, et al. Decline in cognitive function in older adults with early-stage breast cancer after adjuvant treatment. Oncologist. 2016. https://doi.org/10.1634/theoncologist.2016-0014.

  • Le Saux O, Falandry C, Gan HK, et al. Inclusion of elderly patients in oncology clinical trials. Ann Oncol. 2016. https://doi.org/10.1093/annonc/mdw259.

  • Lichtman S. Call for changes in clinical trial reporting of older patients with cancer. J Clin Oncol. 2012a;30:893–4.

    Article  Google Scholar 

  • Lichtman SM. Clinical trial design in older adults with cancer – the need for new paradigms. J Geriatr Oncol. 2012b;3:368–75.

    Article  Google Scholar 

  • Lichtman S. Geriatric oncology and clinical trials. ASCO Educ Book. 2015;127–31.

    Google Scholar 

  • Mackey R, Martin M, Pienkowski T, et al. Adjuvant docetaxel, doxorubicin, and cyclophosphamide in node-positive breast cancer: 10-year follow-up of the phase 3 randomised BCIRG 001 trial. Lancet Oncol. 2013;14(1):72–80.

    Article  CAS  Google Scholar 

  • McGale P, Cutter D, Darby SC, et al. Can observational data replace randomized trials? J Clin Oncol. 2016;34(7):3355–6.

    Article  Google Scholar 

  • Mohile S, Wildiers H. A call for observational cohort studies in geriatric oncology. J Geriatr Oncol. 2012;3:291–3.

    Article  Google Scholar 

  • Pallis AG, Ring A, Fortpied C, et al. EORTC workshop on clinical trial methodology in older individuals with a diagnosis of solid tumors. Ann Oncol. 2011;22(8):1922–6.

    Article  CAS  Google Scholar 

  • Peyrade F, Jardin F, Thieblemont C, et al. Attenuated immunochemotherapy regimen (RminiCHOP) in elderly patients older than 80 years with diffuse large B-cell lymphoma: a multicentre, single-arm, phase 2 trial. Lancet Oncol. 2011;12:460–8.

    Article  CAS  Google Scholar 

  • Reuben DB, Rubenstein LV, Hirsch SH, et al. Value of functional status as a predictor of mortality: results of a prospective study. Am J Med. 1992;93:663–9.

    Article  CAS  Google Scholar 

  • Scher K, Hurria A. Under-representation of older adults in cancer registration trials: known problem, little progress. J Clin Oncol. 2012;30:2036–8.

    Article  Google Scholar 

  • Stadler WM, Figlin RA, McDermott DF, et al. Safety and efficacy results of the advanced renal cell carcinoma sorafenib expanded access program in North America. Cancer. 2010;116(5):1272–80.

    Article  CAS  Google Scholar 

  • Stolberg H, Norman G, Trop I. Fundamentals of clinical research for radiologists. Randomized controlled trials. AJR. 2004;183:1539–44.

    Article  Google Scholar 

  • Thall PF, Wathen JK. Practical Bayesian adaptive randomisation in clinical trials. Eur J Cancer. 2007;43(5):859–66.

    Article  Google Scholar 

  • The Australian Government, the Treasury. Data source from the World Population Prospects Database, United Nations Population Division. 2016. http://demographics.treasury.gov.au/content/_download/australias_demographic_challenges/html/adc-04.asp. Downloaded 16 Nov 2016. Accessed 10 Aug 2017.

  • Torgerson D. The use of Zelen’s design in randomised trials. BJOG. 2004;111(1):2.

    Article  Google Scholar 

  • United Nations. World Population Prospects: the 2010 revision. 2010. http://esa.un.org/unpd/wpp. Accessed 10 Aug 2017.

  • Wheelwright S, Darlington A-S, Fitzsimmons D, et al. International validation of the EORTC QLQ-ELD14 questionnaire for assessment of health-related quality of life elderly patients with cancer. Br J Cancer. 2013;109(4):852–8.

    Article  CAS  Google Scholar 

  • Wildiers H, Highley MS, de Bruijn EA, et al. Pharmacology of anticancer drugs in the elderly population. Clin Pharmacokinet. 2003;42:1213–42.

    Article  CAS  Google Scholar 

  • Wildiers H, Mauer M, Pallis A, et al. End points and trial design in geriatric oncology research: a joint European organisation for research and treatment of cancer – alliance for clinical trials in oncology – International Society of Geriatric Oncology position article. J Clin Oncol. 2013;31(29):3711–8.

    Article  Google Scholar 

  • Woodward RM, Menzin J, Neumann PJ. Quality-adjusted life years in cancer: pros, cons, and alternatives. Eur J Cancer Care. 2013;22(1):12–9.

    Article  CAS  Google Scholar 

  • Yellen SB, Cella DF, Leslie WT. Age and clinical decision making in oncology patients. J Natl Cancer Inst. 1994;86:1766–70.

    Article  CAS  Google Scholar 

Download references

Acknowledgments

The authors wish to thank Aileen Eiszele for writing assistance.

Author information

Authors and Affiliations

  1. Department of General Medical Oncology, University Hospitals Leuven and Katholieke Universiteit Leuven (KU Leuven), Leuven, Belgium

    Hans Wildiers

  2. Lyon-Sud University Hospital and Lyon 1 University, Lyon, France

    Olivia Le Saux

Authors
  1. Hans Wildiers
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Olivia Le Saux
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Hans Wildiers .

Editor information

Editors and Affiliations

  1. Senior Adult Oncology Program, Moffitt Cancer Center, University of South Florida, Tampa, FL, USA

    Martine Extermann

Section Editor information

  1. Research Center on Aging, Department of Medicine, Immunology Graduate Programme, Faculty of Medicine, University of Sherbrooke, Sherbrooke, Quebec, Canada

    Tamas Fulop

  2. Moffitt Cancer Center, University of South Florida, Tampa, FL, USA

    Martine Extermann

Rights and permissions

Reprints and permissions

Copyright information

© 2020 Springer Nature Switzerland AG

About this entry

Check for updates. Verify currency and authenticity via CrossMark

Cite this entry

Wildiers, H., Le Saux, O. (2020). Research Methods: Clinical Trials in Geriatric Oncology. In: Extermann, M. (eds) Geriatric Oncology . Springer, Cham. https://doi.org/10.1007/978-3-319-57415-8_5

Download citation

  • DOI: https://doi.org/10.1007/978-3-319-57415-8_5

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-57414-1

  • Online ISBN: 978-3-319-57415-8

  • eBook Packages: MedicineReference Module Medicine

Publish with us

Policies and ethics

Search

Navigation