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Published in: Drugs & Aging 1/2019

01-01-2019 | Leading Article

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

Authors: Zeina Al-Mansour, Linda Pang, Venu Bathini

Published in: Drugs & Aging | Issue 1/2019

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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.
Literature
1.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
2.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
3.
go back to reference Yancik R. Cancer burden in the aged: an epidemiologic and demographic overview. Cancer. 1997;80(7):1273–83.CrossRefPubMed Yancik R. Cancer burden in the aged: an epidemiologic and demographic overview. Cancer. 1997;80(7):1273–83.CrossRefPubMed
4.
go back to reference Yancik R, Ries LAG. Cancer in older persons: an international issue in an aging world. Semin Oncol. 2004;31(2):128–36.CrossRefPubMed Yancik R, Ries LAG. Cancer in older persons: an international issue in an aging world. Semin Oncol. 2004;31(2):128–36.CrossRefPubMed
5.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
6.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
7.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
9.
11.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
12.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
13.
go back to reference 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.CrossRefPubMedPubMedCentral 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.CrossRefPubMedPubMedCentral
14.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
15.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
16.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
17.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
18.
go back to reference 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.CrossRefPubMedPubMedCentral 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.CrossRefPubMedPubMedCentral
19.
go back to reference 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.CrossRefPubMedPubMedCentral 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.CrossRefPubMedPubMedCentral
20.
go back to reference 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.CrossRefPubMedPubMedCentral 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.CrossRefPubMedPubMedCentral
21.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
22.
go back to reference 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.CrossRefPubMedPubMedCentral 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.CrossRefPubMedPubMedCentral
23.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
24.
go back to reference 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.CrossRefPubMedPubMedCentral 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.CrossRefPubMedPubMedCentral
25.
go back to reference 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.CrossRefPubMedPubMedCentral 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.CrossRefPubMedPubMedCentral
26.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
27.
go back to reference 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.CrossRefPubMedPubMedCentral 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.CrossRefPubMedPubMedCentral
28.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
29.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
30.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
31.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
32.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
33.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
34.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
35.
go back to reference 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.CrossRefPubMedPubMedCentral 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.CrossRefPubMedPubMedCentral
36.
go back to reference Launay-Vacher V, Deray G. Hypertension and proteinuria: a class-effect of antiangiogenic therapies. Anticancer Drugs. 2009;20(1):81–2.CrossRefPubMed Launay-Vacher V, Deray G. Hypertension and proteinuria: a class-effect of antiangiogenic therapies. Anticancer Drugs. 2009;20(1):81–2.CrossRefPubMed
37.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
38.
go back to reference Harari PM. Epidermal growth factor receptor inhibition strategies in oncology. Endocr Relat Cancer. 2004;11(4):689–708.CrossRefPubMed Harari PM. Epidermal growth factor receptor inhibition strategies in oncology. Endocr Relat Cancer. 2004;11(4):689–708.CrossRefPubMed
39.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
40.
go back to reference 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.CrossRefPubMedPubMedCentral 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.CrossRefPubMedPubMedCentral
41.
go back to reference 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.CrossRefPubMedPubMedCentral 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.CrossRefPubMedPubMedCentral
42.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
43.
go back to reference 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.CrossRefPubMedPubMedCentral 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.CrossRefPubMedPubMedCentral
44.
go back to reference 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.CrossRefPubMedPubMedCentral 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.CrossRefPubMedPubMedCentral
45.
go back to reference 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.CrossRefPubMedPubMedCentral 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.CrossRefPubMedPubMedCentral
46.
47.
go back to reference 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.CrossRefPubMedPubMedCentral 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.CrossRefPubMedPubMedCentral
48.
go back to reference 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.CrossRefPubMedPubMedCentral 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.CrossRefPubMedPubMedCentral
49.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
50.
go back to reference 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.CrossRef 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.CrossRef
51.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
52.
go back to reference 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.PubMedPubMedCentral 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.PubMedPubMedCentral
53.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
54.
go back to reference Strevel EL, Ing DJ, Siu LL. Molecularly targeted oncology therapeutics and prolongation of the QT interval. J Clin Oncol. 2007;25(22):3362–71.CrossRefPubMed Strevel EL, Ing DJ, Siu LL. Molecularly targeted oncology therapeutics and prolongation of the QT interval. J Clin Oncol. 2007;25(22):3362–71.CrossRefPubMed
55.
go back to reference Rhea IB, Oliveira GH. Cardiotoxicity of novel targeted chemotherapeutic agents. Curr Treat Options Cardiovasc Med. 2018;20(7):53.CrossRefPubMed Rhea IB, Oliveira GH. Cardiotoxicity of novel targeted chemotherapeutic agents. Curr Treat Options Cardiovasc Med. 2018;20(7):53.CrossRefPubMed
56.
go back to reference 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.CrossRefPubMedPubMedCentral 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.CrossRefPubMedPubMedCentral
57.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
58.
go back to reference 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.CrossRefPubMedPubMedCentral 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.CrossRefPubMedPubMedCentral
59.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
60.
go back to reference Cella DF, Bonomi AE. Measuring quality of life: 1995 update. Oncol Huntingt. 1995;9(11 Suppl):47–60. Cella DF, Bonomi AE. Measuring quality of life: 1995 update. Oncol Huntingt. 1995;9(11 Suppl):47–60.
61.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
62.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
63.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
64.
go back to reference 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.CrossRefPubMedPubMedCentral 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.CrossRefPubMedPubMedCentral
65.
go back to reference 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.CrossRefPubMedPubMedCentral 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.CrossRefPubMedPubMedCentral
66.
go back to reference Müller L, Pawelec G. Aging and immunity—impact of behavioral intervention. Brain Behav Immun. 2014;39:8–22.CrossRefPubMed Müller L, Pawelec G. Aging and immunity—impact of behavioral intervention. Brain Behav Immun. 2014;39:8–22.CrossRefPubMed
67.
go back to reference Banchereau J, Steinman RM. Dendritic cells and the control of immunity. Nature. 1998;392(6673):245–52.CrossRefPubMed Banchereau J, Steinman RM. Dendritic cells and the control of immunity. Nature. 1998;392(6673):245–52.CrossRefPubMed
68.
go back to reference Banchereau J, Palucka AK. Dendritic cells as therapeutic vaccines against cancer. Nat Rev Immunol. 2005;5(4):296–306.CrossRefPubMed Banchereau J, Palucka AK. Dendritic cells as therapeutic vaccines against cancer. Nat Rev Immunol. 2005;5(4):296–306.CrossRefPubMed
69.
go back to reference Palucka K, Banchereau J. Dendritic cells: a link between innate and adaptive immunity. J Clin Immunol. 1999;19(1):12–25.CrossRefPubMed Palucka K, Banchereau J. Dendritic cells: a link between innate and adaptive immunity. J Clin Immunol. 1999;19(1):12–25.CrossRefPubMed
70.
71.
go back to reference Yung RL. Changes in immune function with age. Rheum Dis Clin N Am. 2000;26(3):455–73.CrossRef Yung RL. Changes in immune function with age. Rheum Dis Clin N Am. 2000;26(3):455–73.CrossRef
72.
go back to reference Grolleau A, Sloan A, Mulé JJ. Dendritic cell-based vaccines for cancer therapy. Cancer Treat Res. 2005;123:181–205.CrossRefPubMed Grolleau A, Sloan A, Mulé JJ. Dendritic cell-based vaccines for cancer therapy. Cancer Treat Res. 2005;123:181–205.CrossRefPubMed
73.
go back to reference 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.CrossRefPubMedPubMedCentral 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.CrossRefPubMedPubMedCentral
74.
go back to reference 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.CrossRefPubMedPubMedCentral 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.CrossRefPubMedPubMedCentral
76.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
77.
go back to reference Hurez V, Padrón ÁS, Svatek RS, Curiel TJ. Considerations for successful cancer immunotherapy in aged hosts. Clin Exp Immunol. 2017;187(1):53–63.CrossRefPubMed Hurez V, Padrón ÁS, Svatek RS, Curiel TJ. Considerations for successful cancer immunotherapy in aged hosts. Clin Exp Immunol. 2017;187(1):53–63.CrossRefPubMed
78.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
79.
80.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
81.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
82.
go back to reference 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.CrossRef 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.CrossRef
83.
go back to reference 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.CrossRefPubMedPubMedCentral 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.CrossRefPubMedPubMedCentral
84.
go back to reference 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.CrossRefPubMedPubMedCentral 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.CrossRefPubMedPubMedCentral
85.
go back to reference 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.CrossRefPubMedPubMedCentral 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.CrossRefPubMedPubMedCentral
86.
go back to reference Clegg A, Young J, Iliffe S, Rikkert MO, Rockwood K. Frailty in elderly people. Lancet. 2013;381(9868):752–62.CrossRefPubMed Clegg A, Young J, Iliffe S, Rikkert MO, Rockwood K. Frailty in elderly people. Lancet. 2013;381(9868):752–62.CrossRefPubMed
87.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
88.
go back to reference 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.CrossRefPubMedPubMedCentral 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.CrossRefPubMedPubMedCentral
89.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
90.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
91.
go back to reference 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.CrossRefPubMedPubMedCentral 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.CrossRefPubMedPubMedCentral
92.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
93.
go back to reference 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.CrossRefPubMedPubMedCentral 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.CrossRefPubMedPubMedCentral
94.
go back to reference 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. 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.
95.
go back to reference 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.CrossRef 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.CrossRef
96.
go back to reference 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.PubMedPubMedCentral 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.PubMedPubMedCentral
97.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
98.
go back to reference 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.CrossRefPubMedPubMedCentral 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.CrossRefPubMedPubMedCentral
99.
go back to reference 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.CrossRefPubMedPubMedCentral 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.CrossRefPubMedPubMedCentral
100.
go back to reference 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.CrossRefPubMedPubMedCentral 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.CrossRefPubMedPubMedCentral
101.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
102.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
103.
go back to reference 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.CrossRefPubMedPubMedCentral 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.CrossRefPubMedPubMedCentral
104.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
105.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
106.
go back to reference 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.CrossRefPubMedPubMedCentral 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.CrossRefPubMedPubMedCentral
107.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
108.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
109.
go back to reference Extermann M, Hurria A. Comprehensive geriatric assessment for older patients with cancer. J Clin Oncol. 2007;25(14):1824–31.CrossRefPubMed Extermann M, Hurria A. Comprehensive geriatric assessment for older patients with cancer. J Clin Oncol. 2007;25(14):1824–31.CrossRefPubMed
110.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
111.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
112.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
Metadata
Title
Novel Cancer Therapeutics in Geriatrics: What is Unique to the Aging Patient?
Authors
Zeina Al-Mansour
Linda Pang
Venu Bathini
Publication date
01-01-2019
Publisher
Springer International Publishing
Published in
Drugs & Aging / Issue 1/2019
Print ISSN: 1170-229X
Electronic ISSN: 1179-1969
DOI
https://doi.org/10.1007/s40266-018-0619-2

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