Clinical pharmacology of oncology agents in older adults: A comprehensive review of how chronologic and functional age can influence treatment-related effects

Siegel, 2016, Cancer statistics, 2016, CA Cancer J Clin, 66, 7, 10.3322/caac.21332 Scher, 2012, Under-representation of older adults in cancer registration trials: known problem, little progress, J Clin Oncol, 30, 2036, 10.1200/JCO.2012.41.6727 Le Saux, 2016, Inclusion of elderly patients in oncology clinical trials, Ann Oncol, 27, 1799, 10.1093/annonc/mdw259 Talarico, 2004, 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, 22, 4626, 10.1200/JCO.2004.02.175 2013 Hurria, 2015, Improving the evidence base for treating older adults with cancer: American Society of Clinical Oncology statement, J Clin Oncol, 33, 3826, 10.1200/JCO.2015.63.0319 Network National Comprehensive Cancer. NCCN Clinical Practice Guidelines in Oncology: Older Adult Oncology [Accessed September 1, 2017]. Wildiers, 2014, International Society of Geriatric Oncology consensus on geriatric assessment in older patients with cancer, J Clin Oncol, 32, 2595, 10.1200/JCO.2013.54.8347 Rubenstein, 1991, Impacts of geriatric evaluation and management programs on defined outcomes: overview of the evidence, J Am Geriatr Soc, 39, 8S, 10.1111/j.1532-5415.1991.tb05927.x Hurria, 2008, Clinical pharmacology of cancer therapies in older adults, Br J Cancer, 98, 517, 10.1038/sj.bjc.6604201 Gonsalves, 2011, Targeted anti-cancer therapy in the elderly, Crit Rev Oncol Hematol, 78, 227, 10.1016/j.critrevonc.2010.06.001 Shi, 2008, The clinical implications of ageing for rational drug therapy, Eur J Clin Pharmacol, 64, 183, 10.1007/s00228-007-0422-1 Korc-Grodzicki, 2014, Prescribing for older patients with cancer, Clin Adv Hematol Oncol, 12, 309 Kinirons, 2004, Drug metabolism and ageing, Br J Clin Pharmacol, 57, 540, 10.1111/j.1365-2125.2004.02096.x Schmucker, 2001, Liver function and phase I drug metabolism in the elderly: a paradox, Drugs Aging, 18, 837, 10.2165/00002512-200118110-00005 Venook, 2003, A phase I and pharmacokinetic study of irinotecan in patients with hepatic or renal dysfunction or with prior pelvic radiation: CALGB 9863, Ann Oncol, 14, 1783, 10.1093/annonc/mdg493 U.S. Department of Health and Human Services Food and Drug Administration Popa, 2014, Potential drug interactions and chemotoxicity in older patients with cancer receiving chemotherapy, J Geriatr Oncol, 5, 307, 10.1016/j.jgo.2014.04.002 Riechelmann, 2007, Potential drug interactions and duplicate prescriptions among cancer patients, J Natl Cancer Inst, 99, 592, 10.1093/jnci/djk130 Nightingale, 2018, The prevalence of major drug-drug interactions in older adults with cancer and the role of clinical decision support software, J Geriatr Oncol, 10.1016/j.jgo.2018.02.001 Scripture, 2006, Drug interactions in cancer therapy, Nat Rev Cancer, 6, 546, 10.1038/nrc1887 Riechelmann, 2009, Drug interactions in oncology: how common are they?, Ann Oncol, 20, 1907, 10.1093/annonc/mdp369 Segal, 2014, Oral chemotherapy food and drug interactions: a comprehensive review of the literature, J Oncol Pract, 10, e255, 10.1200/JOP.2013.001183 Jamani, 2016, High prevalence of potential drug-drug interactions in patients with castration-resistant prostate cancer treated with abiraterone acetate, Eur J Clin Pharmacol, 72, 1391, 10.1007/s00228-016-2120-3 Lichtman, 2007, International Society of Geriatric Oncology (SIOG) recommendations for the adjustment of dosing in elderly cancer patients with renal insufficiency, Eur J Cancer, 43, 1, 10.1016/j.ejca.2006.11.004 Muss, 2007, Toxicity of older and younger patients treated with adjuvant chemotherapy for node-positive breast cancer: the Cancer and Leukemia Group B Experience, J Clin Oncol, 25, 3699, 10.1200/JCO.2007.10.9710 Owyong, 2018, Overcoming barriers of age to enhance efficacy of cancer immunotherapy: the clout of the extracellular matrix, Front Cell Dev Biol, 6, 19, 10.3389/fcell.2018.00019 2016 Hida, 2017, Alectinib versus crizotinib in patients with ALK-positive non-small-cell lung cancer (J-ALEX): an open-label, randomised phase 3 trial, Lancet, 390, 29, 10.1016/S0140-6736(17)30565-2 Peters, 2017, Alectinib versus crizotinib in untreated ALK-positive non–small-cell lung cancer, N Engl J Med, 377, 829, 10.1056/NEJMoa1704795 2017 Kim, 2017, Brigatinib in patients with crizotinib-refractory anaplastic lymphoma kinase-positive non-small-cell lung cancer: a randomized, multicenter phase II trial, J Clin Oncol, 35, 2490, 10.1200/JCO.2016.71.5904 2017 2017 Blackhall, 2013, Crizotinib safety profile in elderly and non-elderly patients with advanced ALK+ non-small cell lung cancer, 11 2017 Cortes, 2012, Bosutinib versus imatinib in newly diagnosed chronic-phase chronic myeloid leukemia: results from the BELA trial, J Clin Oncol, 30, 3486, 10.1200/JCO.2011.38.7522 2017 Latagliata, 2011, Dasatinib is safe and effective in unselected chronic myeloid leukaemia elderly patients resistant/intolerant to imatinib, Leuk Res, 35, 1164, 10.1016/j.leukres.2011.05.015 2017 Latagliata, 2013, Imatinib in very elderly patients with chronic myeloid leukemia in chronic phase: a retrospective study, Drugs Aging, 30, 629, 10.1007/s40266-013-0088-6 Iurlo, 2016, Imatinib and polypharmacy in very old patients with chronic myeloid leukemia: effects on response rate, toxicity and outcome, Oncotarget, 7, 80083, 10.18632/oncotarget.11657 2017 Lipton, 2008, Nilotinib in elderly chronic myeloid leukemia patients in chronic phase (CML-CP) with imatinib resistance or intolerance: efficacy and safety analysis, Blood, 112, 3233, 10.1182/blood.V112.11.3233.3233 Giles, 2017, Impact of age on efficacy and toxicity of nilotinib in patients with chronic myeloid leukemia in chronic phase: ENEST1st subanalysis, J Cancer Res Clin Oncol, 10.1007/s00432-017-2402-x 2016 Cortes, 2013, PACE, a phase 2 trial of ponatinib in Philadelphia chromosome-positive leukemias, N Engl J Med, 369, 1783, 10.1056/NEJMoa1306494 2017 Ouellet, 2014, Population pharmacokinetics of dabrafenib, a BRAF inhibitor: effect of dose, time, covariates, and relationship with its metabolites, J Clin Pharmacol, 54, 696, 10.1002/jcph.263 2017 Zhang, 2017, Clin pharmaco kinet, Clin Pharmacokinet Vemurafenib, 1 Larkin, 2014, Vemurafenib in patients with BRAF(V600) mutated metastatic melanoma: an open-label, multicentre, safety study, Lancet Oncol, 15, 10.1016/S1470-2045(14)70051-8 2016 Sequist, 2013, Phase III study of afatinib or cisplatin plus pemetrexed in patients with metastatic lung adenocarcinoma with EGFR mutations, J Clin Oncol, 31, 3327, 10.1200/JCO.2012.44.2806 Wu, 2014, Afatinib versus cisplatin plus gemcitabine for first-line treatment of Asian patients with advanced non-small-cell lung cancer harbouring EGFR mutations (LUX-Lung 6): an open-label, randomised phase 3 trial, Lancet Oncol, 15, 213, 10.1016/S1470-2045(13)70604-1 2016 Wheatley-Price, 2008, Erlotinib for advanced non-small-cell lung cancer in the elderly: an analysis of the National Cancer Institute of Canada Clinical Trials Group Study BR.21, J Clin Oncol, 26, 2350, 10.1200/JCO.2007.15.2280 Yamada, 2016, Phase II trial of Erlotinib in elderly patients with previously treated non-small cell lung Cancer: results of the lung oncology Group in Kyushu (LOGiK-0802), Anticancer Res, 36, 2881 2017 Crown, 2008, Pooled analysis of diarrhea events in patients with cancer treated with lapatinib, Breast Cancer Res Treat, 112, 317, 10.1007/s10549-007-9860-9 Perez, 2008, Cardiac safety of lapatinib: pooled analysis of 3689 patients enrolled in clinical trials, Mayo Clin Proc, 83, 679, 10.1016/S0025-6196(11)60896-3 2016 Gridelli, 2014, Phase II randomized study of vandetanib plus gemcitabine or gemcitabine plus placebo as first-line treatment of advanced non-small-cell lung cancer in elderly patients, J Thorac Oncol, 9, 733, 10.1097/JTO.0000000000000120 2016 2017 2014 Miyake, 2016, Efficacy and safety of axitinib in elderly patients with metastatic renal cell carcinoma, Med Oncol, 33, 95, 10.1007/s12032-016-0813-1 2016 2017 2017 2013 Eisen, 2008, Sorafenib for older patients with renal cell carcinoma: a subset analysis from a randomized trial, J Natl Cancer Inst, 100, 1454, 10.1093/jnci/djn319 2015 Hutson, 2014, Efficacy and safety of sunitinib in elderly patients with metastatic renal cell carcinoma, Br J Cancer, 110, 1125, 10.1038/bjc.2013.832 2016 2016 2017 2016 2016 2017 2015 2017 2017 2016 2017 Rituxan (rituximab) [prescribing information]. South San Francisco, CA: Genentech Inc; March 2016. Fischer, 2016, Long-term remissions after FCR chemoimmunotherapy in previously untreated patients with CLL: Updated results of the CLL8 trial, Blood, 127, 208, 10.1182/blood-2015-06-651125 2017 Singh, 2015, Targeted agents for HER2-positive breast cancer: optimal use in older adults, Drugs Aging, 12, 975, 10.1007/s40266-015-0326-1 Andrews, 2015, Treating with checkpoint inhibitors—figure $1 million per patient, Am Health Drug Benefits, 8, 9 2017 2017 2017 2017 2017 2017 2014 Abdel-Qadir, 2016, The risk of myocardial infarction with aromatase inhibitors relative to tamoxifen in post-menopausal women with early stage breast cancer, Eur J Cancer, 68, 11, 10.1016/j.ejca.2016.08.022 2011 2017 Smith, 2015, Efficacy and safety of abiraterone acetate in elderly (75 years or older) chemotherapy naïve patients with metastatic castration resistant prostate cancer, J Urol, 194, 1277, 10.1016/j.juro.2015.07.004 2017 D'Amico, 2007, Influence of androgen suppression therapy for prostate cancer on the frequency and timing of fatal myocardial infarctions, J Clin Oncol, 25, 2420, 10.1200/JCO.2006.09.3369 2017 2016 2015 Zhang, 2013, Long-term efficacy and safety of arsenic trioxide for first-line treatment of elderly patients with newly diagnosed acute promyelocytic leukemia, Cancer, 119, 115, 10.1002/cncr.27650 2017 Richardson, 2007, Safety and efficacy of bortezomib in high-risk and elderly patients with relapsed multiple myeloma, Br J Hae Matol, 137, 429, 10.1111/j.1365-2141.2007.06585.x 2017 2016 Pritchard, 2013, Safety and efficacy of everolimus with exemestane vs. exemestane alone in elderly patients with HER2-negative, hormone receptor-positive breast cancer in BOLERO-2, Clin Breast Cancer, 13, 421, 10.1016/j.clbc.2013.08.011 2016 2017 Lynparza (olaparib tablets) [prescribing information]. Wilmington, DE: AstraZeneca Pharmaceuticals; August 2017. 2017 2016 2017 2017 Levakov, 2016, Safety profile of temsirolimus in patients with metastatic renal cell carcinoma, J BUON, 21, 1442 2017 Chang, 2016, Safety and efficacy of vismodegib in patients aged ≥ 65 years with advanced basal cell carcinoma, Oncotarget, 7, 76118, 10.18632/oncotarget.12660 2016 Laurenti, 2015, Bendamustine in combination with rituximab for elderly patients with previously untreated B-cell chronic lymphocytic leukemia: a retrospective analysis of real-life practice in Italian hematology departments, Leuk Res, 39, 1068, 10.1016/j.leukres.2015.07.009 2015 2010 Ramalingman, 2008, Comparison of outcomes for elderly patients treated with weekly paclitaxel in combination with carboplatin versus the standard 3- weekly paclitaxel and carboplatin for advanced non-small cell lung cancer, Cancer, 113, 542, 10.1002/cncr.23583 2015 Lichtman, 1992, Use of cisplatin for elderly patients, Age Aging, 21, 202, 10.1093/ageing/21.3.202 Hrushesky, 1984, Lack of age-dependent cisplatin nephrotoxicity, Am J Med, 76, 579, 10.1016/0002-9343(84)90280-8 Cubillo, 2001, Renal tolerance to cisplatin in patients 70 years and older, Am J Clin Oncol, 24, 192, 10.1097/00000421-200104000-00018 Aronoff, 2007, vol. 100, 172 2015 Floyd, 2006, Hepatotoxicity of chemotherapy, Semin Oncol, 33, 50, 10.1053/j.seminoncol.2005.11.002 Wildiers, 2003, Pharmacology of anticancer drugs in the elderly population, Clin Pharmacokinet, 42, 1213, 10.2165/00003088-200342140-00003 2014 De Pas, 2000, Ifosfamide in the elderly: clinical considerations for a better drug management, Crit Rev Oncol Hematol, 33, 129, 10.1016/S1040-8428(99)00060-8 2015 Baek, 2010, Oxaliplatin-induced chronic peripheral neurotoxicity: a prospective analysis in patients with colorectal cancer, Cancer Res Treat, 42, 185, 10.4143/crt.2010.42.4.185 Goldberg, 2006, Pooled analysis of safety and efficacy of oxaliplatin plus fluorouracil/leucovorin administered bimonthly in elderly patients with colorectal cancer, J Clin Oncol, 24, 4085, 10.1200/JCO.2006.06.9039 2016 Ershler, 2006, Capecitabine use in geriatric oncology: an analysis of current safety, efficacy, and quality of life data, Crit Rev Oncol Hematol, 58, 68, 10.1016/j.critrevonc.2005.08.006 Feliu, 2005, Capecitabine as first-line treatment for patients older than 70 years with metastatic colorectal cancer: an oncopaz cooperative group study, J Clin Oncol, 23, 3104, 10.1200/JCO.2005.06.035 Bajetta, 2005, Safety and efficacy of two different doses of capecitabine in the treatment of advanced breast cancer in older women, J Clin Oncol, 23, 2155, 10.1200/JCO.2005.02.167 2013 Lindner, 2008, AraU accumulation in patients with renal insufficiency as a potential mechanism for cytarabine neurotoxicity, Int J Hematol, 88, 381, 10.1007/s12185-008-0171-7 2016 Lim, 2017, Feasibility of Modified FOLFOX in Elderly Patients Aged ≥ 80 Years with Metastatic Gastric Cancer or Colorectal Cancer, Oncology, 93, 115, 10.1159/000471767 Folprecht, 2004, Efficacy of 5-fluorouracil-based chemotherapy in elderly patients with metastatic colorectal cancer: a pooled analysis of clinical trials, Ann Oncol, 15, 1330, 10.1093/annonc/mdh344 2014 Zhu, 2009, High-dose methotrexate for elderly patients with primary CNS lymphoma, Neuro Oncol, 11, 211, 10.1215/15228517-2008-067 2015 Paz-Ares, 2017, Meta-analysis examining impact of age on overall survival with pemetrexed for the treatment of advanced non-squamous non-small cell lung cancer, Lung Cancer, 104, 45, 10.1016/j.lungcan.2016.12.007 Hata, 2017, Pemetrexed monotherapy for chemo-naïve elderly (aged≥ 80) patients with non-squamous non-small cell lung cancer: results from combined analysis of two single arm phase II studies (HANSHIN002 and 003), Cancer Chemother Pharmacol, 79, 689, 10.1007/s00280-017-3259-z 2016 2017 2016 Muss, 2014, Eribulin monotherapy in patients aged 70 years and older with metastatic breast Cancer, Oncologist, 19, 318, 10.1634/theoncologist.2013-0282 2011 Vahdat, 2013, Efficay and safety of ixabepilone plus capecitabine in eldery patients with anthracycline and taxane pretreated metastatic breast cancer, J Geriatric Oncol, 4, 352 2015 Jin, 2016, A retrospective analysis of safety and efficacy of weekly nab-paclitaxel as second-line chemotherapy in elderly patients with advanced squamous non-small cell lung carcinoma, Clin Interv Aging, 11, 167 2016 Stamatoullas, 2015, Outcome of patients older than 60 years with classical Hodgkin lymphoma treated with front line ABVD chemotherapy: frequent pulmonary events suggest limiting the use of bleomycin in the elderly, Br J Haematol, 170, 179, 10.1111/bjh.13419 2013 Löwenberg, 2009, High-dose daunorubicin in older patients with acute myeloid leukemia, N Engl J Med, 361, 1235, 10.1056/NEJMoa0901409 Aapro, 2010, Anthracycline cardiotoxicity in the elderly cancer patient: a SIOG expert position paper, Ann Oncol, 22, 257, 10.1093/annonc/mdq609 2012 Ibrahim NK, Frye DK, Buzdar AU, Walters RS, Hortobagyi GN. Doxorubicin-based chemotherapy in elderly patients with metastatic breast cancer: tolerance and outcome. Arch Intern Med 1996 Apr 22;156(8):882–8. 2016 Folprecht, 2008, Irinotecan/fluorouracil combination in first-line therapy of older and younger patients with metastatic colorectal cancer: combined analysis of 2,691 patients in randomized controlled trials, J Clin Oncol, 26, 1443, 10.1200/JCO.2007.14.0509 Sasaki, 2013, Concomitant polypharmacy is associated with irinotecan-related adverse drug reactions in patients with cancer, Int J Clin Oncol, 18, 735, 10.1007/s10147-012-0425-5 2013 Tirelli, 1998, CHOP is the standard regimen in patients ≥ 70 years of age with intermediate-grade and high-grade non-Hodgkin's lymphoma: results of a randomized study of the European Organization for Research and Treatment of Cancer lymphoma cooperative study group, J Clin Oncol, 16, 27, 10.1200/JCO.1998.16.1.27 Sargent, 2001, A pooled analysis of adjuvant chemotherapy for resected colon cancer in elderly patients, N Engl J Med, 345, 1091, 10.1056/NEJMoa010957 Jorgensen, 2013, Adjuvant chemotherapy for colorectal cancer: age differences in factors influencing patients' treatment decisions, Pat Prefer Adher, 7, 827, 10.2147/PPA.S50970 Ananda, 2008, Patient age and comorbidity are major determinants of adjuvant chemotherapy use for stage III colon cancer in routine clinical practice, J Clin Oncol, 26, 4516, 10.1200/JCO.2008.18.7443 Wedding, 2007, Physicians' judgement and comprehensive geriatric assessment (CGA) select different patients as fit for chemotherapy, Crit Rev Oncol Hematol, 64, 1, 10.1016/j.critrevonc.2007.05.001 Linn, 1968, Cumulative illness rating scale, J Am Geriatr Soc, 16, 622, 10.1111/j.1532-5415.1968.tb02103.x Hurria, 2011, Predicting chemotherapy toxicity in older adults with cancer: a prospective multicenter study, J Clin Oncol, 29, 3457, 10.1200/JCO.2011.34.7625 American Geriatrics Society, 2015, Updated beers criteria for potentially inappropriate medication use in older adults, J Am Geriatr Soc, 63, 2227 O'Mahony, 2015, STOPP/START criteria for potentially inappropriate prescribing in older people: version 2, Age Ageing, 44, 213, 10.1093/ageing/afu145 Nightingale, 2015, Evaluation of a pharmacist-led medication assessment used to identify prevalence of and associations with polypharmacy and potentially inappropriate medication use among ambulatory senior adults with cancer, J Clin Oncol, 33, 1453, 10.1200/JCO.2014.58.7550 Prithviraj, 2012, Patient characteristics associated with polypharmacy and inappropriate prescribing of medications among older adults with cancer, J Geriatr Oncol, 3, 228, 10.1016/j.jgo.2012.02.005 Turner, 2016, Polypharmacy cut-points in older people with cancer: how many medications are too many?, Support Care Cancer, 24, 1831, 10.1007/s00520-015-2970-8 Maggiore, 2014, Polypharmacy and potentially inappropriate medication use in older adults with cancer undergoing chemotherapy: effect on chemotherapy-related toxicity and hospitalization during treatment, J Am Geriatr Soc, 62, 1505, 10.1111/jgs.12942 Bushardt, 2008, Polypharmacy: misleading, but manageable, Clin Interv Aging, 3, 383, 10.2147/CIA.S2468 Dimitrow, 2011, Comparison of prescribing criteria to evaluate the appropriateness of drug treatment in individuals aged 65 and older: a systematic review, J Am Geriatr Soc, 59, 1521, 10.1111/j.1532-5415.2011.03497.x Maggiore, 2012, Use of complementary medications among older adults with cancer, Cancer, 118, 4815, 10.1002/cncr.27427 Wyatt, 1999, Complementary therapy use among older cancer patients, Cancer Pract, 7, 136, 10.1046/j.1523-5394.1999.07305.x Nightingale, 2015, A pharmacist-led medication assessment used to determine a more precise estimation of the prevalence of complementary and alternative medication (CAM) use among ambulatory senior adults with cancer, J Geriatric Oncol, 6, 411, 10.1016/j.jgo.2015.07.003 Nightingale, 2017, The impact of polypharmacy on patient outcomes in older adults with cancer, Cancer J, 23, 211, 10.1097/PPO.0000000000000277 Girre, 2011, Potential drug interactions in elderly cancer patients, Crit Rev Oncol Hematol, 78, 220, 10.1016/j.critrevonc.2010.05.004 Verbrugghe, 2013, Determinants and associated factors influencing medication adherence and persistence to oral anticancer drugs: a systematic review, Cancer Treat Rev, 39, 610, 10.1016/j.ctrv.2012.12.014 Morisky, 1986, Concurrent and predictive validity of a self-reported measure of medication adherence, Med Care, 24, 67, 10.1097/00005650-198601000-00007 MacLaughlin, 2005, Assessing medication adherence in the elderly, Drugs Aging, 22, 231, 10.2165/00002512-200522030-00005 Hurria, 2016, Validation of a prediction tool for chemotherapy toxicity in older adults with cancer, J Clin Oncol, 34, 2366, 10.1200/JCO.2015.65.4327 Extermann, 2012, Predicting the risk of chemotherapy toxicity in older patients: the chemotherapy risk assessment scale for high-age patients (CRASH) score, Cancer, 118, 3377, 10.1002/cncr.26646