Optimising Clinical Trial Design in Older Cancer Patients
Abstract
:1. Introduction
2. Implementation of Comprehensive Geriatric Assessment
3. Clinical Trial Methodology
4. Quality of Life Endpoints
5. Conclusions
Author Contributions
Funding
Conflicts of Interest
References
- Cancer Factsheet: Overview & Most Common Cancers [Internet]; National Cancer Registry Ireland: Cork Ireland, 2017; Available online: https://www.Ncri.Ie/sites/ncri/files/factsheets/all%20cancers_0.Pdf (accessed on 24 May 2018).
- Scher, K.S.; Hurria, A. Under-representation of older adults in cancer registration trials: Known problem, little progress. J. Clin. Oncol. Off. J. Am. Soc. Clin. Oncol. 2012, 30, 2036–2038. [Google Scholar] [CrossRef] [PubMed]
- Talarico, L.; Chen, G.; Pazdur, R. Enrollment of elderly patients in clinical trials for cancer drug registration: A 7-year experience by the us food and drug administration. J. Clin. Oncol. 2004, 22, 4626–4631. [Google Scholar] [CrossRef] [PubMed]
- Younger, E.; Litiere, S.; Le Cesne, A.; Mir, O.; Gelderblom, H.; Italiano, A.; Marreaud, S.; Jones, R.L.; Gronchi, A.; van der Graaf, W.T.A. Outcomes of elderly patients with advanced soft tissue sarcoma treated with first-line chemotherapy: A pooled analysis of 12 eortc soft tissue and bone sarcoma group trials. Oncologist 2018. [Google Scholar] [CrossRef] [PubMed]
- Fang, P.; He, W.; Gomez, D.R.; Hoffman, K.E.; Smith, B.D.; Giordano, S.H.; Jagsi, R.; Smith, G.L. Influence of age on guideline-concordant cancer care for elderly patients in the united states. Int. J. Radiat. Oncol. Biol. Phys. 2017, 98, 748–757. [Google Scholar] [CrossRef] [PubMed]
- Arciero, V.S.; Cheng, S.; Mason, R.; McDonald, E.; Saluja, R.; Chan, K.K.W. Do older and younger patients derive similar survival benefits from novel oncology drugs? A systematic review and meta-analysis. Age Ageing 2018. [Google Scholar] [CrossRef] [PubMed]
- Zhao, C.J.; Li, S.; Liu, Q. Meta-analysis of molecular targeted agents in the treatment of elderly patients with metastatic colorectal cancer: Does the age matter? J. Cancer Res. Ther. 2018, 14, S79–S84. [Google Scholar] [CrossRef] [PubMed]
- Buechel, M.; McGinnis, A.; Vesely, S.K.; Wade, K.S.; Moore, K.N.; Gunderson, C.C. Consideration of older patients for enrollment in phase 1 clinical trials: Exploring treatment related toxicities and outcomes. Gynecol. Oncol. 2018, 149, 28–32. [Google Scholar] [CrossRef] [PubMed]
- World Health Organisation (WHO). Health Statistics and Health Information Systems. Definition of an Older or Elderly Person. Available online: https://www.scribd.com/document/190077600/WHO-Definition-of-an-Older-or-Elderly-Person (accessed on 12 June 2018).
- Gorman, M. Development and the rights of older people. In The Ageing and Development Report: Poverty, Independence and the World‘s Older People; Judith, R., Ewing, T., Eds.; Routledge: London, UK, 2017. [Google Scholar]
- Wildiers, H.; Heeren, P.; Puts, M.; Topinkova, E.; Janssen-Heijnen, M.L.; Extermann, M.; Falandry, C.; Artz, A.; Brain, E.; Colloca, G. International society of geriatric oncology consensus on geriatric assessment in older patients with cancer. J. Clin. Oncol. 2014, 32, 2595–2603. [Google Scholar] [CrossRef] [PubMed]
- Lewis, J.H.; Kilgore, M.L.; Goldman, D.P.; Trimble, E.L.; Kaplan, R.; Montello, M.J.; Housman, M.G.; Escarce, J.J. Participation of patients 65 years of age or older in cancer clinical trials. J. Clin. Oncol. 2003, 21, 1383–1389. [Google Scholar] [CrossRef] [PubMed]
- Lichtman, S.M. Clinical trial design in older adults with cancer—The need for new paradigms. J. Geriatr. Oncol. 2012, 3, 368–375. [Google Scholar] [CrossRef]
- Hurria, A.; Lachs, M.S.; Cohen, H.J.; Muss, H.B.; Kornblith, A.B. Geriatric assessment for oncologists: Rationale and future directions. Crit. Rev. Oncol. Hematol. 2006, 59, 211–217. [Google Scholar] [CrossRef] [PubMed]
- Fried, L.P.; Tangen, C.M.; Walston, J.; Newman, A.B.; Hirsch, C.; Gottdiener, J.; Seeman, T.; Tracy, R.; Kop, W.J.; Burke, G.; et al. Frailty in older adults: Evidence for a phenotype. J. Gerontol. Ser. A Biol. Sci. Med. Sci. 2001, 56, M146–M156. [Google Scholar] [CrossRef]
- Clegg, A.; Young, J.; Iliffe, S.; Rikkert, M.O.; Rockwood, K. Frailty in elderly people. Lancet 2013, 381, 752–762. [Google Scholar] [CrossRef] [Green Version]
- Balducci, L.; Extermann, M. Management of cancer in the older person: A practical approach. Oncologist 2000, 5, 224–237. [Google Scholar] [CrossRef] [PubMed]
- Wildiers, H.; Mauer, M.; Pallis, A.; Hurria, A.; Mohile, S.G.; Luciani, A.; Curigliano, G.; Extermann, M.; Lichtman, S.M.; Ballman, K. 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, 3711–3718. [Google Scholar] [CrossRef] [PubMed]
- Soto-Perez-De-Celis, E.; Lichtman, S.M. Considerations for clinical trial design in older adults with cancer. Expert Opin. Investig. Drugs 2017, 26, 1099–1102. [Google Scholar] [CrossRef] [PubMed]
- Kelly, C.M.; Shahrokni, A. Moving beyond karnofsky and ECOG performance status assessments with new technologies. J. Oncol. 2016, 2016, 6186543. [Google Scholar] [CrossRef] [PubMed]
- Corre, R.; Greillier, L.; Le Caer, H.; Audigier-Valette, C.; Baize, N.; Berard, H.; Falchero, L.; Monnet, I.; Dansin, E.; Vergnenegre, A.; et al. Use of a comprehensive geriatric assessment for the management of elderly patients with advanced non-small-cell lung cancer: The phase iii randomized esogia-gfpc-gecp 08-02 study. J. Clin. Oncol. Off. J. Am. Soc. Clin. Oncol. 2016, 34, 1476–1483. [Google Scholar] [CrossRef] [PubMed]
- Mertens, C.; Le Caer, H.; Ortholan, C.; Blot, E.; Even, C.; Rousselot, H.; Peyrade, F.; Sire, C.; Cupissol, D.; Pointreau, Y. 1050pdthe elan-oncoval (elderly head and neck cancer-oncology evaluation) study: Evaluation of the feasibility of a suited geriatric assessment for use by oncologists to classify patients as fit or unfit. Ann. Oncol. 2017, 28. [Google Scholar] [CrossRef]
- O’Donovan, A.; Mohile, S.G.; Leech, M. Expert consensus panel guidelines on geriatric assessment in oncology. Eur. J. Cancer Care 2015, 24, 574–589. [Google Scholar] [CrossRef] [PubMed]
- Mohile, S.G.; Velarde, C.; Hurria, A.; Magnuson, A.; Lowenstein, L.; Pandya, C.; O’Donovan, A.; Gorawara-Bhat, R.; Dale, W. Geriatric assessment-guided care processes for older adults: A delphi consensus of geriatric oncology experts. J. Natl. Compr. Cancer Netw. JNCCN 2015, 13, 1120–1130. [Google Scholar] [CrossRef]
- Pottel, L.; Lycke, M.; Boterberg, T.; Pottel, H.; Goethals, L.; Duprez, F.; Van Den Noortgate, N.; De Neve, W.; Rottey, S.; Geldhof, K.; et al. Serial comprehensive geriatric assessment in elderly head and neck cancer patients undergoing curative radiotherapy identifies evolution of multidimensional health problems and is indicative of quality of life. Eur. J. Cancer Care 2014, 23, 401–412. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Pallis, A.G.; Ring, A.; Fortpied, C.; Penninckx, B.; Van Nes, M.C.; Wedding, U.; vonMinckwitz, G.; Johnson, C.D.; Wyld, L.; Timmer-Bonte, A.; et al. Eortc workshop on clinical trial methodology in older individuals with a diagnosis of solid tumors. Ann. Oncol. 2011, 22, 1922–1926. [Google Scholar] [CrossRef] [PubMed]
- Hamaker, M.E.; Stauder, R.; van Munster, B.C. Exclusion of older patients from ongoing clinical trials for hematological malignancies: An evaluation of the national institutes of health clinical trial registry. Oncologist 2014, 19, 1069–1075. [Google Scholar] [CrossRef] [PubMed]
- Hurria, A.; Wong, F.L.; Villaluna, D.; Bhatia, S.; Chung, C.T.; Mortimer, J.; Hurvitz, S.; Naeim, A. Role of age and health in treatment recommendations for older adults with breast cancer: The perspective of oncologists and primary care providers. J. Clin. Oncol. 2008, 26, 5386–5392. [Google Scholar] [CrossRef] [PubMed]
- Berry, M.F.; Worni, M.; Pietrobon, R.; D’amico, T.A.; Akushevich, I. Variability in the treatment of elderly patients with stage iiia (n2) non–small-cell lung cancer. J. Thorac. Oncol. 2013, 8, 744–752. [Google Scholar] [CrossRef] [PubMed]
- Hurria, A.; Dale, W.; Mooney, M.; Rowland, J.H.; Ballman, K.V.; Cohen, H.J.; Muss, H.B.; Schilsky, R.L.; Ferrell, B.; Extermann, M. Designing therapeutic clinical trials for older and frail adults with cancer: U13 conference recommendations. J. Clin. Oncol. 2014, 32, 2587. [Google Scholar] [CrossRef] [PubMed]
- Seymour, M.T.; Thompson, L.C.; Wasan, H.S.; Middleton, G.; Brewster, A.E.; Shepherd, S.F.; O’Mahony, M.S.; Maughan, T.S.; Parmar, M.; Langley, R.E. Chemotherapy options in elderly and frail patients with metastatic colorectal cancer (mrc focus2): An open-label, randomised factorial trial. Lancet 2011, 377, 1749–1759. [Google Scholar] [CrossRef]
- Sekeres, M.; Stone, R.; Zahrieh, D.; Neuberg, D.; Morrison, V.; De Angelo, D.; Galinsky, I.; Lee, S. Decision-making and quality of life in older adults with acute myeloid leukemia or advanced myelodysplastic syndrome. Leukemia 2004, 18, 809–816. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Fried, T.R.; Bradley, E.H.; Towle, V.R.; Allore, H. Understanding the treatment preferences of seriously ill patients. N. Engl. J. Med. 2002, 346, 1061–1066. [Google Scholar] [CrossRef] [PubMed]
- Gotze, H.; Kohler, N.; Taubenheim, S.; Lordick, F.; Mehnert, A. Polypharmacy, limited activity, fatigue and insomnia are the most frequent symptoms and impairments in older hematological cancer survivors (70+): Findings from a register-based study on physical and mental health. J. Geriatr. Oncol. 2018. [Google Scholar] [CrossRef] [PubMed]
- Johnson, C.; Fitzsimmons, D.; Gilbert, J.; Arrarras, J.-I.; Hammerlid, E.; Bredart, A.; Ozmen, M.; Dilektasli, E.; Coolbrandt, A.; Kenis, C. Development of the european organisation for research and treatment of cancer quality of life questionnaire module for older people with cancer: The eortc qlq-eld15. Eur. J. Cancer 2010, 46, 2242–2252. [Google Scholar] [CrossRef] [PubMed]
- Schwartz, C.; Cole, B.; Vickrey, B.; Gelber, R. The q-twist approach to assessing health-related quality of life in epilepsy. Qual. Life Res. 1995, 4, 135–141. [Google Scholar] [CrossRef] [PubMed]
- Freedman, R.A.; Dockter, T.J.; Lafky, J.M.; Hurria, A.; Muss, H.J.; Cohen, H.J.; Jatoi, A.; Kemeny, M.M.; Ruddy, K.J. Promoting accrual of older patients with cancer to clinical trials: An alliance for clinical trials in oncology member survey (a171602). Oncologist 2018. [Google Scholar] [CrossRef] [PubMed]
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Whelehan, S.; Lynch, O.; Treacy, N.; Gleeson, C.; Oates, A.; O’Donovan, A. Optimising Clinical Trial Design in Older Cancer Patients. Geriatrics 2018, 3, 34. https://doi.org/10.3390/geriatrics3030034
Whelehan S, Lynch O, Treacy N, Gleeson C, Oates A, O’Donovan A. Optimising Clinical Trial Design in Older Cancer Patients. Geriatrics. 2018; 3(3):34. https://doi.org/10.3390/geriatrics3030034
Chicago/Turabian StyleWhelehan, Shóna, Orlaith Lynch, Niall Treacy, Ciara Gleeson, Andrea Oates, and Anita O’Donovan. 2018. "Optimising Clinical Trial Design in Older Cancer Patients" Geriatrics 3, no. 3: 34. https://doi.org/10.3390/geriatrics3030034