Advertisement

Drugs & Aging

, Volume 36, Issue 1, pp 1–11 | Cite as

Novel Cancer Therapeutics in Geriatrics: What is Unique to the Aging Patient?

  • Zeina Al-MansourEmail author
  • Linda Pang
  • Venu Bathini
Leading Article

Abstract

With the worldwide trend of aging populations, the number of older adults who develop and survive cancer is likely to increase. In the last decade, oncology drug development has shifted away from conventional chemotherapeutics towards agents that can ‘target’ a driver mutation of a specific cancer or ‘unleash’ the patient’s native immune system to attack the cancer—so-called molecularly targeted therapies and immunotherapeutics. The basic algorithms of cancer treatment in elderly patients are essentially the same as in younger patients; however, one needs to pay exceptional attention to the effects of co-morbidities, interaction with other drugs, and the organ function reserve of an older individual before determining his/her ‘eligibility’ for a specific cancer treatment modality. Despite the growing evidence of safety and effectiveness of combination chemotherapy in fit elderly patients, the data are still lacking concerning the use of currently approved targeted agents and immunotherapies. The current evidence, though limited, suggests reasonable tolerability with comparable efficacy in patients > 65 years old treated with immune-based therapies to that in younger controls; however, it is unclear if this leads to significant patient-relevant gains such as improved survival with an acceptable quality of life. Nonetheless, these newer agents remain better tolerated than cytotoxic chemotherapy in clinical practice, particularly in older patients. Alternatively, a personalized approach for elderly patients with consideration of the incidence and management of adverse effects, as well as strategies for optimizing efficacy in the context of an aging immune system, would be of utmost value in our aging cancer population. Future trials should also explore immune markers to predict response to these therapeutics in elderly patients, taking into consideration the effects of immunosenescence and immune modulation in aging hosts.

Notes

Compliance with Ethical Standards

Funding

No external funding was used in the preparation of this article.

Conflict of interest

Zeina Al-Mansour, Linda Pang, and Venu Bathini declare that they have no conflicts of interest that might be relevant to the contents of this article.

References

  1. 1.
    Smith BD, Smith GL, Hurria A, Hortobagyi GN, Buchholz TA. Future of cancer incidence in the United States: burdens upon an aging, changing nation. J Clin Oncol. 2009;27(17):2758–65.Google Scholar
  2. 2.
    Warren JL, Mariotto AB, Meekins A, Topor M, Brown ML. Current and future utilization of services from medical oncologists. J Clin Oncol. 2008;26(19):3242–7.Google Scholar
  3. 3.
    Yancik R. Cancer burden in the aged: an epidemiologic and demographic overview. Cancer. 1997;80(7):1273–83.Google Scholar
  4. 4.
    Yancik R, Ries LAG. Cancer in older persons: an international issue in an aging world. Semin Oncol. 2004;31(2):128–36.Google Scholar
  5. 5.
    Yee KWL, Pater JL, Pho L, Zee B, Siu LL. Enrollment of older patients in cancer treatment trials in Canada: why is age a barrier? J Clin Oncol. 2003;21(8):1618–23.Google Scholar
  6. 6.
    Kumar A, Soares HP, Balducci L, Djulbegovic B, National Cancer Institute. Treatment tolerance and efficacy in geriatric oncology: a systematic review of phase III randomized trials conducted by five National Cancer Institute-sponsored cooperative groups. J Clin Oncol. 2007;25(10):1272–6.Google Scholar
  7. 7.
    Scher KS, Hurria A. Under-representation of older adults in cancer registration trials: known problem, little progress. J Clin Oncol. 2012;30(17):2036–8.Google Scholar
  8. 8.
    Harman D. The aging process. Proc Natl Acad Sci USA. 1981;78(11):7124–8.Google Scholar
  9. 9.
    Gilchrest BA, Bohr VA. Aging processes, DNA damage, and repair. FASEB J. 1997;11(5):322–30.Google Scholar
  10. 10.
    Nightingale G, Schwartz R, Kachur E, Dixon BN, Cote C, Barlow A, et al. Clinical pharmacology of oncology agents in older adults: a comprehensive review of how chronologic and functional age can influence treatment-related effects. J Geriatr Oncol. 2018.  https://doi.org/10.1016/j.jgo.2018.06.008 (Epub 2018 Jul 12).Google Scholar
  11. 11.
    Sawhney R, Sehl M, Naeim A. Physiologic aspects of aging: impact on cancer management and decision making, part I. Cancer J. 2005;11(6):449–60.Google Scholar
  12. 12.
    Sehl M, Sawhney R, Naeim A. Physiologic aspects of aging: impact on cancer management and decision making, part II. Cancer J. 2005;11(6):461–73.Google Scholar
  13. 13.
    Fuchs CS, Doi T, Jang RW, Muro K, Satoh T, Machado M, et al. Safety and efficacy of pembrolizumab monotherapy in patients with previously treated advanced gastric and gastroesophageal junction cancer: phase 2 clinical KEYNOTE-059 trial. JAMA Oncol. 2018;4(5):e180013.Google Scholar
  14. 14.
    Ribas A, Puzanov I, Dummer R, Schadendorf D, Hamid O, Robert C, et al. Pembrolizumab versus investigator-choice chemotherapy for ipilimumab-refractory melanoma (KEYNOTE-002): a randomised, controlled, phase 2 trial. Lancet Oncol. 2015;16(8):908–18.Google Scholar
  15. 15.
    Robert C, Schachter J, Long GV, Arance A, Grob JJ, Mortier L, et al. Pembrolizumab versus ipilimumab in advanced melanoma. N Engl J Med. 2015;372(26):2521–32.Google Scholar
  16. 16.
    Herbst RS, Baas P, Kim D-W, Felip E, Pérez-Gracia JL, Han J-Y, et al. Pembrolizumab versus docetaxel for previously treated, PD-L1-positive, advanced non-small-cell lung cancer (KEYNOTE-010): a randomised controlled trial. Lancet. 2016;387(10027):1540–50.Google Scholar
  17. 17.
    Langer CJ, Gadgeel SM, Borghaei H, Papadimitrakopoulou VA, Patnaik A, Powell SF, et al. Carboplatin and pemetrexed with or without pembrolizumab for advanced, non-squamous non-small-cell lung cancer: a randomised, phase 2 cohort of the open-label KEYNOTE-021 study. Lancet Oncol. 2016;17(11):1497–508.Google Scholar
  18. 18.
    Bellmunt J, de Wit R, Vaughn DJ, Fradet Y, Lee J-L, Fong L, et al. Pembrolizumab as second-line therapy for advanced urothelial carcinoma. N Engl J Med. 2017;376(11):1015–26.Google Scholar
  19. 19.
    Nghiem PT, Bhatia S, Lipson EJ, Kudchadkar RR, Miller NJ, Annamalai L, et al. PD-1 blockade with pembrolizumab in advanced Merkel-cell carcinoma. N Engl J Med. 2016;374(26):2542–52.Google Scholar
  20. 20.
    Chen R, Zinzani PL, Fanale MA, Armand P, Johnson NA, Brice P, et al. Phase II study of the efficacy and safety of pembrolizumab for relapsed/refractory classic Hodgkin lymphoma. J Clin Oncol. 2017;35(19):2125–32.Google Scholar
  21. 21.
    Balar AV, Galsky MD, Rosenberg JE, Powles T, Petrylak DP, Bellmunt J, et al. Atezolizumab as first-line treatment in cisplatin-ineligible patients with locally advanced and metastatic urothelial carcinoma: a single-arm, multicentre, phase 2 trial. Lancet. 2017;389(10064):67–76.Google Scholar
  22. 22.
    Rosenberg JE, Hoffman-Censits J, Powles T, van der Heijden MS, Balar AV, Necchi A, et al. Atezolizumab in patients with locally advanced and metastatic urothelial carcinoma who have progressed following treatment with platinum-based chemotherapy: a single-arm, multicentre, phase 2 trial. Lancet. 2016;387(10031):1909–20.Google Scholar
  23. 23.
    Ansell SM, Lesokhin AM, Borrello I, Halwani A, Scott EC, Gutierrez M, et al. PD-1 blockade with nivolumab in relapsed or refractory Hodgkin’s lymphoma. N Engl J Med. 2015;372(4):311–9.Google Scholar
  24. 24.
    Brahmer J, Reckamp KL, Baas P, Crinò L, Eberhardt WEE, Poddubskaya E, et al. Nivolumab versus docetaxel in advanced squamous-cell non-small-cell lung cancer. N Engl J Med. 2015;373(2):123–35.Google Scholar
  25. 25.
    Larkin J, Chiarion-Sileni V, Gonzalez R, Grob JJ, Cowey CL, Lao CD, et al. Combined nivolumab and ipilimumab or monotherapy in untreated melanoma. N Engl J Med. 2015;373(1):23–34.Google Scholar
  26. 26.
    El-Khoueiry AB, Sangro B, Yau T, Crocenzi TS, Kudo M, Hsu C, et al. Nivolumab in patients with advanced hepatocellular carcinoma (CheckMate 040): an open-label, non-comparative, phase 1/2 dose escalation and expansion trial. Lancet. 2017;389(10088):2492–502.Google Scholar
  27. 27.
    Rizvi NA, Mazières J, Planchard D, Stinchcombe TE, Dy GK, Antonia SJ, et al. Activity and safety of nivolumab, an anti-PD-1 immune checkpoint inhibitor, for patients with advanced, refractory squamous non-small-cell lung cancer (CheckMate 063): a phase 2, single-arm trial. Lancet Oncol. 2015;16(3):257–65.Google Scholar
  28. 28.
    Lowrance WT, Ordoñez J, Udaltsova N, Russo P, Go AS. CKD and the risk of incident cancer. J Am Soc Nephrol JASN. 2014;25(10):2327–34.Google Scholar
  29. 29.
    Orskov B, Sørensen VR, Feldt-Rasmussen B, Strandgaard S. Changes in causes of death and risk of cancer in Danish patients with autosomal dominant polycystic kidney disease and end-stage renal disease. Nephrol Dial Transplant. 2012;27(4):1607–13.Google Scholar
  30. 30.
    Wong G, Hayen A, Chapman JR, Webster AC, Wang JJ, Mitchell P, et al. Association of CKD and cancer risk in older people. J Am Soc Nephrol JASN. 2009;20(6):1341–50.Google Scholar
  31. 31.
    Launay-Vacher V, Aapro M, De Castro G, Cohen E, Deray G, Dooley M, et al. Renal effects of molecular targeted therapies in oncology: a review by the Cancer and the Kidney International Network (C-KIN). Ann Oncol. 2015;26(8):1677–84.Google Scholar
  32. 32.
    Swedko PJ, Clark HD, Paramsothy K, Akbari A. Serum creatinine is an inadequate screening test for renal failure in elderly patients. Arch Intern Med. 2003;163(3):356–60.Google Scholar
  33. 33.
    Launay-Vacher V, Chatelut E, Lichtman SM, Wildiers H, Steer C, Aapro M, et al. Renal insufficiency in elderly cancer patients: International Society of Geriatric Oncology clinical practice recommendations. Ann Oncol. 2007;18(8):1314–21.Google Scholar
  34. 34.
    Launay-Vacher V, Oudard S, Janus N, Gligorov J, Pourrat X, Rixe O, et al. Prevalence of renal insufficiency in cancer patients and implications for anticancer drug management: the renal insufficiency and anticancer medications (IRMA) study. Cancer. 2007;110(6):1376–84.Google Scholar
  35. 35.
    Eremina V, Jefferson JA, Kowalewska J, Hochster H, Haas M, Weisstuch J, et al. VEGF inhibition and renal thrombotic microangiopathy. N Engl J Med. 2008;358(11):1129–36.Google Scholar
  36. 36.
    Launay-Vacher V, Deray G. Hypertension and proteinuria: a class-effect of antiangiogenic therapies. Anticancer Drugs. 2009;20(1):81–2.Google Scholar
  37. 37.
    Thariat J, Azzopardi N, Peyrade F, Launay-Vacher V, Santini J, Lecomte T, et al. Cetuximab pharmacokinetics in end-stage kidney disease under hemodialysis. J Clin Oncol. 2008;26(25):4223–5.Google Scholar
  38. 38.
    Harari PM. Epidermal growth factor receptor inhibition strategies in oncology. Endocr Relat Cancer. 2004;11(4):689–708.Google Scholar
  39. 39.
    Vermorken JB, Stöhlmacher-Williams J, Davidenko I, Licitra L, Winquist E, Villanueva C, et al. Cisplatin and fluorouracil with or without panitumumab in patients with recurrent or metastatic squamous-cell carcinoma of the head and neck (SPECTRUM): an open-label phase 3 randomised trial. Lancet Oncol. 2013;14(8):697–710.Google Scholar
  40. 40.
    Dimke H, van der Wijst J, Alexander TR, Meijer IMJ, Mulder GM, van Goor H, et al. Effects of the EGFR inhibitor erlotinib on magnesium handling. J Am Soc Nephrol. 2010;21(8):1309–16.Google Scholar
  41. 41.
    Bou Matar RN, Klein JD, Sands JM. Erlotinib preserves renal function and prevents salt retention in doxorubicin treated nephrotic rats. PLoS One. 2013;8(1):e54738.Google Scholar
  42. 42.
    Shen H, Yang Z, Zhao W, Zhang Y, Rodrigues AD. Assessment of vandetanib as an inhibitor of various human renal transporters: inhibition of multidrug and toxin extrusion as a possible mechanism leading to decreased cisplatin and creatinine clearance. Drug Metab Dispos Biol Fate Chem. 2013;41(12):2095–103.Google Scholar
  43. 43.
    Brahmer JR, Tykodi SS, Chow LQM, Hwu W-J, Topalian SL, Hwu P, et al. Safety and activity of anti-PD-L1 antibody in patients with advanced cancer. N Engl J Med. 2012;366(26):2455–65.Google Scholar
  44. 44.
    Brahmer JR, Drake CG, Wollner I, Powderly JD, Picus J, Sharfman WH, et al. Phase I study of single-agent anti-programmed death-1 (MDX-1106) in refractory solid tumors: safety, clinical activity, pharmacodynamics, and immunologic correlates. J Clin Oncol. 2010;28(19):3167–75.Google Scholar
  45. 45.
    Topalian SL, Hodi FS, Brahmer JR, Gettinger SN, Smith DC, McDermott DF, et al. Safety, activity, and immune correlates of anti-PD-1 antibody in cancer. N Engl J Med. 2012;366(26):2443–54.Google Scholar
  46. 46.
    Ewer SM, Ewer MS. Cardiotoxicity profile of trastuzumab. Drug Saf. 2008;31(6):459–67.Google Scholar
  47. 47.
    Romond EH, Jeong J-H, Rastogi P, Swain SM, Geyer CE, Ewer MS, et al. Seven-year follow-up assessment of cardiac function in NSABP B-31, a randomized trial comparing doxorubicin and cyclophosphamide followed by paclitaxel (ACP) with ACP plus trastuzumab as adjuvant therapy for patients with node-positive, human epidermal growth factor receptor 2-positive breast cancer. J Clin Oncol. 2012;30(31):3792–9.Google Scholar
  48. 48.
    Perez EA, Suman VJ, Davidson NE, Sledge GW, Kaufman PA, Hudis CA, et al. Cardiac safety analysis of doxorubicin and cyclophosphamide followed by paclitaxel with or without trastuzumab in the North Central Cancer Treatment Group N9831 adjuvant breast cancer trial. J Clin Oncol. 2008;26(8):1231–8.Google Scholar
  49. 49.
    Serrano C, Cortés J, De Mattos-Arruda L, Bellet M, Gómez P, Saura C, et al. Trastuzumab-related cardiotoxicity in the elderly: a role for cardiovascular risk factors. Ann Oncol. 2012;23(4):897–902.Google Scholar
  50. 50.
    Hamnvik O-PR, Choueiri TK, Turchin A, McKay RR, Goyal L, Davis M, et al. Clinical risk factors for the development of hypertension in patients treated with inhibitors of the VEGF signaling pathway. Cancer. 2015;15, 121(2):311–9.Google Scholar
  51. 51.
    McMullen JR, Boey EJH, Ooi JYY, Seymour JF, Keating MJ, Tam CS. Ibrutinib increases the risk of atrial fibrillation, potentially through inhibition of cardiac PI3K-Akt signaling. Blood. 2014;124(25):3829–30.Google Scholar
  52. 52.
    Wiczer TE, Levine LB, Brumbaugh J, Coggins J, Zhao Q, Ruppert AS, et al. Cumulative incidence, risk factors, and management of atrial fibrillation in patients receiving ibrutinib. Blood Adv. 2017;1(20):1739–48.Google Scholar
  53. 53.
    Lenihan DJ, Alencar AJ, Yang D, Kurzrock R, Keating MJ, Duvic M. Cardiac toxicity of alemtuzumab in patients with mycosis fungoides/Sézary syndrome. Blood. 2004;104(3):655–8.Google Scholar
  54. 54.
    Strevel EL, Ing DJ, Siu LL. Molecularly targeted oncology therapeutics and prolongation of the QT interval. J Clin Oncol. 2007;25(22):3362–71.Google Scholar
  55. 55.
    Rhea IB, Oliveira GH. Cardiotoxicity of novel targeted chemotherapeutic agents. Curr Treat Options Cardiovasc Med. 2018;20(7):53.Google Scholar
  56. 56.
    Johnson DB, Balko JM, Compton ML, Chalkias S, Gorham J, Xu Y, et al. Fulminant myocarditis with combination immune checkpoint blockade. N Engl J Med. 2016;375(18):1749–55.Google Scholar
  57. 57.
    Escudier M, Cautela J, Malissen N, Ancedy Y, Orabona M, Pinto J, et al. Clinical features, management, and outcomes of immune checkpoint inhibitor-related cardiotoxicity. Circulation. 2017;136(21):2085–7.Google Scholar
  58. 58.
    Heinzerling L, Ott PA, Hodi FS, Husain AN, Tajmir-Riahi A, Tawbi H, et al. Cardiotoxicity associated with CTLA4 and PD1 blocking immunotherapy. J Immunother Cancer. 2016;4:50.Google Scholar
  59. 59.
    Yancik R, Ries LA. Cancer in older persons. Magnitude of the problem–how do we apply what we know? Cancer. 1994;74(7 Suppl):1995–2003.Google Scholar
  60. 60.
    Cella DF, Bonomi AE. Measuring quality of life: 1995 update. Oncol Huntingt. 1995;9(11 Suppl):47–60.Google Scholar
  61. 61.
    Cella DF, Bonomi AE, Lloyd SR, Tulsky DS, Kaplan E, Bonomi P. Reliability and validity of the Functional Assessment of Cancer Therapy-Lung (FACT-L) quality of life instrument. Lung Cancer. 1995;12(3):199–220.Google Scholar
  62. 62.
    Pisu M, Azuero A, Halilova KI, Williams CP, Kenzik KM, Kvale EA, et al. Most impactful factors on the health-related quality of life of a geriatric population with cancer. Cancer. 2018;124(3):596–605.Google Scholar
  63. 63.
    Langa KM, Fendrick AM, Chernew ME, Kabeto MU, Paisley KL, Hayman JA. Out-of-pocket health-care expenditures among older Americans with cancer. Value Health. 2004;7(2):186–94.Google Scholar
  64. 64.
    Ramsey S, Blough D, Kirchhoff A, Kreizenbeck K, Fedorenko C, Snell K, et al. Washington State cancer patients found to be at greater risk for bankruptcy than people without a cancer diagnosis. Health Aff (Millwood). 2013;32(6):1143–52.Google Scholar
  65. 65.
    Pinti M, Appay V, Campisi J, Frasca D, Fülöp T, Sauce D, et al. Aging of the immune system: focus on inflammation and vaccination. Eur J Immunol. 2016;46(10):2286–301.Google Scholar
  66. 66.
    Müller L, Pawelec G. Aging and immunity—impact of behavioral intervention. Brain Behav Immun. 2014;39:8–22.Google Scholar
  67. 67.
    Banchereau J, Steinman RM. Dendritic cells and the control of immunity. Nature. 1998;392(6673):245–52.Google Scholar
  68. 68.
    Banchereau J, Palucka AK. Dendritic cells as therapeutic vaccines against cancer. Nat Rev Immunol. 2005;5(4):296–306.Google Scholar
  69. 69.
    Palucka K, Banchereau J. Dendritic cells: a link between innate and adaptive immunity. J Clin Immunol. 1999;19(1):12–25.Google Scholar
  70. 70.
    Miller RA. The aging immune system: primer and prospectus. Science. 1996;273(5271):70–4.Google Scholar
  71. 71.
    Yung RL. Changes in immune function with age. Rheum Dis Clin N Am. 2000;26(3):455–73.Google Scholar
  72. 72.
    Grolleau A, Sloan A, Mulé JJ. Dendritic cell-based vaccines for cancer therapy. Cancer Treat Res. 2005;123:181–205.Google Scholar
  73. 73.
    Grolleau-Julius A, Harning EK, Abernathy LM, Yung RL. Impaired dendritic cell function in aging leads to defective antitumor immunity. Cancer Res. 2008;68(15):6341–9.Google Scholar
  74. 74.
    Bueno V, Sant’Anna OA, Lord JM. Ageing and myeloid-derived suppressor cells: possible involvement in immunosenescence and age-related disease. Age. 2014;36(6):9729.Google Scholar
  75. 75.
    Orloff M. Melanoma immunotherapy in the elderly. Curr Oncol Rep. 2018;20(2):20.Google Scholar
  76. 76.
    Elias R, Karantanos T, Sira E, Hartshorn KL. Immunotherapy comes of age: immune aging and checkpoint inhibitors. J Geriatr Oncol. 2017;8(3):229–35.Google Scholar
  77. 77.
    Hurez V, Padrón ÁS, Svatek RS, Curiel TJ. Considerations for successful cancer immunotherapy in aged hosts. Clin Exp Immunol. 2017;187(1):53–63.Google Scholar
  78. 78.
    Mannick JB, Del Giudice G, Lattanzi M, Valiante NM, Praestgaard J, Huang B, et al. mTOR inhibition improves immune function in the elderly. Sci Transl Med. 2014;6(268):268ra179.Google Scholar
  79. 79.
    Marrone KA, Forde PM. Cancer immunotherapy in older patients. Cancer J. 2017;23(4):219–22.Google Scholar
  80. 80.
    Daste A, Domblides C, Gross-Goupil M, Chakiba C, Quivy A, Cochin V, et al. Immune checkpoint inhibitors and elderly people: a review. Eur J Cancer. 2017;82:155–66.Google Scholar
  81. 81.
    Borson S, Scanlan J, Brush M, Vitaliano P, Dokmak A. The mini-cog: a cognitive “vital signs” measure for dementia screening in multi-lingual elderly. Int J Geriatr Psychiatry. 2000;15(11):1021–7.Google Scholar
  82. 82.
    Singh H, Kim G, Maher VE, Beaver JA, Pai-Scherf LH, Balasubramaniam S, et al. FDA subset analysis of the safety of nivolumab in elderly patients with advanced cancer. J Clin Oncol. 2016;34(15_Suppl.):10010.Google Scholar
  83. 83.
    Elias R, Giobbie-Hurder A, McCleary NJ, Ott P, Hodi FS, Rahma O. Efficacy of PD-1 and PD-L1 inhibitors in older adults: a meta-analysis. J Immunother Cancer. 2018;6(1):26.Google Scholar
  84. 84.
    Rizvi NA, Hellmann MD, Snyder A, Kvistborg P, Makarov V, Havel JJ, et al. Cancer immunology. Mutational landscape determines sensitivity to PD-1 blockade in non-small cell lung cancer. Science. 2015;348(6230):124–8.Google Scholar
  85. 85.
    Goodman AM, Kato S, Bazhenova L, Patel SP, Frampton GM, Miller V, et al. Tumor mutational burden as an independent predictor of response to immunotherapy in diverse cancers. Mol Cancer Ther. 2017;16(11):2598–608.Google Scholar
  86. 86.
    Clegg A, Young J, Iliffe S, Rikkert MO, Rockwood K. Frailty in elderly people. Lancet. 2013;381(9868):752–62.Google Scholar
  87. 87.
    Woods NF, LaCroix AZ, Gray SL, Aragaki A, Cochrane BB, Brunner RL, et al. Frailty: emergence and consequences in women aged 65 and older in the Women’s Health Initiative Observational Study. J Am Geriatr Soc. 2005;53(8):1321–30.Google Scholar
  88. 88.
    Lakey SL, LaCroix AZ, Gray SL, Borson S, Williams CD, Calhoun D, et al. Antidepressant use, depressive symptoms, and incident frailty in women aged 65 and older from the Women’s Health Initiative Observational Study. J Am Geriatr Soc. 2012;60(5):854–61.Google Scholar
  89. 89.
    Evenhuis HM, Hermans H, Hilgenkamp TIM, Bastiaanse LP, Echteld MA. Frailty and disability in older adults with intellectual disabilities: results from the healthy ageing and intellectual disability study. J Am Geriatr Soc. 2012;60(5):934–8.Google Scholar
  90. 90.
    Cawthon PM, Marshall LM, Michael Y, Dam T-T, Ensrud KE, Barrett-Connor E, et al. Frailty in older men: prevalence, progression, and relationship with mortality. J Am Geriatr Soc. 2007;55(8):1216–23.Google Scholar
  91. 91.
    Bandeen-Roche K, Seplaki CL, Huang J, Buta B, Kalyani RR, Varadhan R, et al. Frailty in older adults: a nationally representative profile in the United States. J Gerontol A Biol Sci Med Sci. 2015;70(11):1427–34.Google Scholar
  92. 92.
    Chrischilles EA, Pendergast JF, Kahn KL, Wallace RB, Moga DC, Harrington DP, et al. Adverse events among the elderly receiving chemotherapy for advanced non-small-cell lung cancer. J Clin Oncol. 2010;28(4):620–7.Google Scholar
  93. 93.
    Wildiers H, Heeren P, Puts M, Topinkova E, Janssen-Heijnen MLG, Extermann M, et al. International Society of Geriatric Oncology consensus on geriatric assessment in older patients with cancer. J Clin Oncol. 2014;32(24):2595–603.Google Scholar
  94. 94.
    Ellis G, Gardner M, Tsiachristas A, Langhorne P, Burke O, Harwood RH, et al. Comprehensive geriatric assessment for older adults admitted to hospital. Cochrane Database Syst Rev. 2017;12(9):CD006211.Google Scholar
  95. 95.
    Pilotto A, Cella A, Pilotto A, Daragjati J, Veronese N, Musacchio C, et al. three decades of comprehensive geriatric assessment: evidence coming from different healthcare settings and specific clinical conditions. J Am Med Dir Assoc. 2017;18(2):192.e1–11.Google Scholar
  96. 96.
    Caillet P, Laurent M, Bastuji-Garin S, Liuu E, Culine S, Lagrange J-L, et al. Optimal management of elderly cancer patients: usefulness of the Comprehensive Geriatric Assessment. Clin Interv Aging. 2014;9:1645–60.Google Scholar
  97. 97.
    Kenis C, Decoster L, Van Puyvelde K, De Grève J, Conings G, Milisen K, et al. Performance of two geriatric screening tools in older patients with cancer. J Clin Oncol. 2014;32(1):19–26.Google Scholar
  98. 98.
    Kirkhus L, Šaltytė Benth J, Rostoft S, Grønberg BH, Hjermstad MJ, Selbæk G, et al. Geriatric assessment is superior to oncologists’ clinical judgement in identifying frailty. Br J Cancer. 2017;117(4):470–7.Google Scholar
  99. 99.
    Hurria A, Togawa K, Mohile SG, Owusu C, Klepin HD, Gross CP, et al. Predicting chemotherapy toxicity in older adults with cancer: a prospective multicenter study. J Clin Oncol. 2011;29(25):3457–65.Google Scholar
  100. 100.
    Hurria A, Mohile S, Gajra A, Klepin H, Muss H, Chapman A, et al. Validation of a prediction tool for chemotherapy toxicity in older adults with cancer. J Clin Oncol. 2016;34(20):2366–71.Google Scholar
  101. 101.
    Feng MA, McMillan DT, Crowell K, Muss H, Nielsen ME, Smith AB. Geriatric assessment in surgical oncology: a systematic review. J Surg Res. 2015;193(1):265–72.Google Scholar
  102. 102.
    Spyropoulou D, Pallis AG, Leotsinidis M, Kardamakis D. Completion of radiotherapy is associated with the Vulnerable Elders Survey-13 score in elderly patients with cancer. J Geriatr Oncol. 2014;5(1):20–5.Google Scholar
  103. 103.
    Betge J, Chi-Kern J, Schulte N, Belle S, Gutting T, Burgermeister E, et al. A multicenter phase 4 geriatric assessment directed trial to evaluate gemcitabine +/- nab-paclitaxel in elderly pancreatic cancer patients (GrantPax). BMC Cancer. 2018;18(1):747.Google Scholar
  104. 104.
    Leighl NB, Zatloukal P, Mezger J, Ramlau R, Moore N, Reck M, et al. Efficacy and safety of bevacizumab-based therapy in elderly patients with advanced or recurrent nonsquamous non-small cell lung cancer in the phase III BO17704 study (AVAiL). J Thorac Oncol. 2010;5(12):1970–6.Google Scholar
  105. 105.
    Brunello A, Basso U, Sacco C, Sava T, De Vivo R, Camerini A, et al. Safety and activity of sunitinib in elderly patients (≥ 70 years) with metastatic renal cell carcinoma: a multicenter study. Ann Oncol. 2013;24(2):336–42.Google Scholar
  106. 106.
    Zhu J, Sharma DB, Gray SW, Chen AB, Weeks JC, Schrag D. Carboplatin and paclitaxel with vs without bevacizumab in older patients with advanced non-small cell lung cancer. JAMA. 2012;307(15):1593–601.Google Scholar
  107. 107.
    Freyer G, Geay J-F, Touzet S, Provencal J, Weber B, Jacquin J-P, et al. Comprehensive geriatric assessment predicts tolerance to chemotherapy and survival in elderly patients with advanced ovarian carcinoma: a GINECO study. Ann Oncol. 2005;16(11):1795–800.Google Scholar
  108. 108.
    Extermann M, Bonetti M, Sledge GW, O’Dwyer PJ, Bonomi P, Benson AB. MAX2—a convenient index to estimate the average per patient risk for chemotherapy toxicity; validation in ECOG trials. Eur J Cancer. 2004;40(8):1193–8.Google Scholar
  109. 109.
    Extermann M, Hurria A. Comprehensive geriatric assessment for older patients with cancer. J Clin Oncol. 2007;25(14):1824–31.Google Scholar
  110. 110.
    Ramjaun A, Nassif MO, Krotneva S, Huang AR, Meguerditchian AN. Improved targeting of cancer care for older patients: a systematic review of the utility of comprehensive geriatric assessment. J Geriatr Oncol. 2013;4(3):271–81.Google Scholar
  111. 111.
    Extermann M, Boler I, Reich RR, Lyman GH, Brown RH, DeFelice J, et al. Predicting the risk of chemotherapy toxicity in older patients: the Chemotherapy Risk Assessment Scale for High-Age Patients (CRASH) score. Cancer. 2012;118(13):3377–86.Google Scholar
  112. 112.
    Soubeyran P, Fonck M, Blanc-Bisson C, Blanc J-F, Ceccaldi J, Mertens C, et al. Predictors of early death risk in older patients treated with first-line chemotherapy for cancer. J Clin Oncol. 2012;30(15):1829–34.Google Scholar
  113. 113.
    National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: older adult oncology. https://www.nccn.org/professionals/physician_gls/pdf/senior.pdf. Accessed 30 Aug 2018.

Copyright information

© Springer Nature Switzerland AG 2018

Authors and Affiliations

  1. 1.Division of Hematology/OncologyUniversity of Massachusetts School of MedicineWorcesterUSA
  2. 2.University of Texas MD Anderson Cancer CenterHoustonUSA
  3. 3.University of Massachusetts School of MedicineWorcesterUSA

Personalised recommendations