Toxicity of Cancer Therapies in Older Patients
Purpose of the Review
In clinical practice, older patients are often undertreated due to underrepresentation in clinical trials and fear of toxicity. Our objective was therefore to review toxicities that are specific to older cancer patients, to review risk factors in order to help physicians guide their decisions, and to review interventions that can be implemented in routine clinical practice to prevent toxicity induced by cancer therapies.
On the whole, reviews report similar number and frequency as well as similar grade 3 or 4 adverse events between subjects older and younger than 65 years.
Yet patients included in clinical trials are often not representative of real-life patients and are often fit older cancer patients. Moreover, tolerance to the additive impact of multiple adverse effects is different between older and younger patients. And specific symptoms such as stomatitis may cause a series of consequences such as dehydration, denutrition, renal insufficiency, and adverse events of renally excreted drugs. Older patients are at high risk of toxicity due to many factors but mainly due to the prevalence of frailty in this population that has been estimated to be around 40% increasing the risk of chemotherapy intolerance. As a consequence, interventions must be implemented according to altered domains of comprehensive geriatric assessment in order to improve anticancer tolerance. These interventions are reviewed here.
KeywordsOlder patients Neoplasms Adverse events Frailty Interventions
Compliance with Ethical Standards
Conflict of Interest
Olivia Le Saux declares that she has no conflict of interest.
Claire Falandry has received research support through grants from Novartis, Pfizer, Chugai, Astellas, and Pierre Fabre, and has received compensation from Roche, Teva, Pfizer, Chugai, Janssen, and Astellas for service as a consultant.
Human and Animal Rights and Informed Consent
This article does not contain any studies with human or animal subjects performed by any of the authors.
Papers of particular interest, published recently, have been highlighted as: • Of importance
- 1.Ries LAG, Eisner MP, Kosary CL, et al. Cancer Statistics Review. Bethesda, MD: National Cancer Institute; 2003. p. 1975–2000.Google Scholar
- 3.• Handforth C, Clegg A, Young C, Simpkins S, Seymour MT, Selby PJ, et al. The prevalence and outcomes of frailty in older cancer patients: a systematic review. Ann Oncol. 2015;26:1091–101. In a systematic review of 20 observational studies, the median reported prevalence of frailty and pre-frailty was 42% and 43% respectively. Treatment complications were more frequent in patients with frailty. Therefore, this review is in favor of performing a proper geriatric assessment of our patients in order to guide therapeutic decisions. CrossRefPubMedGoogle Scholar
- 9.Kozuki T, Nogami N, Kitajima H, Iwasawa S, Sakaida E, Takiguchi Y, et al. Feasibility study of first-line chemotherapy using Pemetrexed and Bevacizumab for advanced or recurrent nonsquamous non-small cell lung cancer in elderly patients TORG1015. BMC Cancer. 2016;16:306.CrossRefPubMedPubMedCentralGoogle Scholar
- 11.• Mariano C, Francl M, Pope J, Wong L, Lim HJ, Lohrisch C. Comparison of toxicity experienced by older versus younger patients enrolled in breast cancer clinical trials. Clin Breast Cancer. 2015;15:73–9. All breast cancer trials open from 1999 to 2012 at BCCA, Vancouver Center, were reviewed. Few older patients were enrolled in cytotoxic chemotherapy trials, but they experienced no more toxicity than did the younger patients. This review suggest that toxicity between older and younger patients is similar in terms of number and frequency. Yet, this review also highlights the fact that older patients are less represented in clinical trials evaluating chemotherapy therefore suggesting that patients included are fit and not representative of routine older patients. CrossRefPubMedGoogle Scholar
- 24.• Laurent M, Paillaud E, Tournigand C, Caillet P, le Thuaut A, Lagrange JL, et al. Assessment of solid cancer treatment feasibility in older patients: a prospective cohort study. Oncologist. 2014;19:275–82. In a prospective French study, older patients with solid malignancies referred to two geriatric oncology clinics between 2007 and 2010 were prospectively included. Planned cancer treatment was feasible in only 59.0% of cases for chemotherapy. CrossRefPubMedPubMedCentralGoogle Scholar
- 26.Chirgwin JH, Giobbie-Hurder A, Coates AS, Price KN, Ejlertsen B, Debled M, et al. Treatment adherence and its impact on disease-free survival in the breast international group 1-98 trial of Tamoxifen and Letrozole, alone and in sequence. J Clin Oncol. 2016;34:2452–9.CrossRefPubMedPubMedCentralGoogle Scholar
- 27.Folprecht G, Seymour MT, Saltz L, Douillard JY, Hecker H, Stephens RJ, et al. 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. 2008;26:1443–51.CrossRefPubMedGoogle Scholar
- 29.Bajetta E, Ravaud A, Bracarda S, Négrier S, Szczylik C, Bellmunt Molins J, Moore N, Pisa P, Escudier BJ Efficacy and safety of first-line bevacizumab (BEV) plus interferon-a2a (IFN) in patients (pts) P65 years with metastatic renal cell carcinoma (mRCC). J Clin Oncol 2008;26. suppl:abstr 5095.Google Scholar
- 35.Asmis TR, Powell E, Karapetis CS, Jonker DJ, Tu D, Jeffery M, et al. Comorbidity, age and overall survival in cetuximab-treated patients with advanced colorectal cancer (ACRC)—results from NCIC CTG CO.17: a phase III trial of cetuximab versus best supportive care. Ann Oncol. 2011;22:118–26.CrossRefPubMedGoogle Scholar
- 38.Hutson TE, Osanto S, Calvo E, et al. Efficacy and safety of everolimus in elderly patients with metastatic renal cell carcinoma (mRCC) after disease progression on VEGFr- TKI therapy [abstract no. 11]. Presented at the 2010 Kidney Cancer Symposium; 2010 Oct 2; Chicago (IL).Google Scholar
- 39.Chiarion Sileni V, Pigozzo J, Ascierto PA, Grimaldi A, Maio M, di Guardo L, et al. Efficacy and safety of ipilimumab in elderly patients with pretreated advanced melanoma treated at Italian centres through the expanded access programme. J Exp Clin Cancer Res. 2014;33:30.CrossRefPubMedPubMedCentralGoogle Scholar
- 43.Walston J, Hadley EC, Ferrucci L, Guralnik JM, Newman AB, Studenski SA, et al. Research agenda for frailty in older adults: toward a better understanding of physiology and etiology: summary from the American Geriatrics Society/National Institute on Aging Research Conference on Frailty in Older Adults. J Am Geriatr Soc. 2006;54:991–1001.CrossRefPubMedGoogle Scholar
- 45.Hilpert F, du Bois A, Greimel ER, Hedderich J, Krause G, Venhoff L, et al. Feasibility, toxicity and quality of life of first-line chemotherapy with platinum/paclitaxel in elderly patients aged >or=70 years with advanced ovarian cancer—a study by the AGO OVAR Germany. Ann Oncol. 2007;18:282–7.CrossRefPubMedGoogle Scholar
- 64.de Glas NA, Hamaker ME, Kiderlen M, de Craen AJM, Mooijaart SP, van de Velde CJH, et al. Choosing relevant endpoints for older breast cancer patients in clinical trials: an overview of all current clinical trials on breast cancer treatment. Breast Cancer Res Treat. 2014;146:591–7.CrossRefPubMedGoogle Scholar
- 66.Simon H, Saghatchian M, Mouysset JL et al. Results from an observational study (NORA) with oral Navelbine in metastatic breast cancer: a sub-analysis in elderly patients. JGO 3 suppl 1: S41-S42.Google Scholar
- 67.• Biganzoli L, Lichtman S, Michel JP, Papamichael D, Quoix E, Walko C, et al. Oral single-agent chemotherapy in older patients with solid tumours: a position paper from the International Society of Geriatric Oncology (SIOG). Eur J Cancer. 2015;51:2491–500. This position paper from the International Society of Geriatric Oncology states that for older cancer patients in general, metronomic chemotherapy combines good tolerability with acceptable activity. CrossRefPubMedGoogle Scholar
- 69.Extermann M, Aapro M, Bernabei R, Cohen HJ, Droz JP, Lichtman S, et al. Use of comprehensive geriatric assessment in older cancer patients: recommendations from the task force on CGA of the International Society of Geriatric Oncology (SIOG). Crit Rev Oncol Hematol. 2005;55:241–52.CrossRefPubMedGoogle Scholar
- 74.• Kalsi T, Babic-Illman G, Ross PJ, Maisey NR, Hughes S, Fields P, et al. The impact of comprehensive geriatric assessment interventions on tolerance to chemotherapy in older people. Br J Cancer. 2015;112:1435–44. In a comparative study of two cohorts of older patients (aged 70+ years) undergoing chemotherapy in a London Hospital, older patients were more likely to complete cancer treatment as planned (odds ratio (OR) 4.14 (95% CI: 1.50–11.42), P=0.006) and fewer required treatment modifications (OR 0.34 (95% CI: 0.16–0.73), P=0.006). In conclusion, geriatrician-led interventions were associated with improved chemotherapy tolerance and should be implemented in routine. CrossRefPubMedPubMedCentralGoogle Scholar
- 77.Hadji P, Aapro MS, Body JJ, Gnant M, Brandi ML, Reginster JY, et al. Management of Aromatase Inhibitor-Associated Bone Loss (AIBL) in postmenopausal women with hormone sensitive breast cancer: joint position statement of the IOF, CABS, ECTS, IEG, ESCEO IMS, and SIOG. J Bone Oncol. 2017;7:1–12.CrossRefPubMedPubMedCentralGoogle Scholar
- 78.Body JJ, Coleman R, Clezardin P, Ripamonti C, Rizzoli R, Aapro M. International Society of Geriatric Oncology. International Society of Geriatric Oncology (SIOG) clinical practice recommendations for the use of bisphosphonates in elderly patients. Eur J Cancer. 2007;43:852–8.CrossRefPubMedGoogle Scholar
- 81.van Dalen EC, Michiels EM, Caron HN, Kremer LC. Different anthracycline derivates for reducing cardiotoxicity in cancer patients. Cochrane Database Syst Rev 2010; CD005006.Google Scholar
- 95.Basch E, Deal AM, Kris MG, Scher HI, Hudis CA, Sabbatini P, et al. Symptom monitoring with patient-reported outcomes during routine cancer treatment: a randomized controlled trial. J Clin Oncol. 2016;34(557):565.Google Scholar
- 98.Zerillo JA, Goldenberg BA, Kotecha RR et al. Interventions to improve oral chemotherapy safety and quality: a systematic review. JAMA Oncol 2017.Google Scholar