Cancer Treatment in the Elderly Jeffrey A. Bubis, DO, FACOI, FACP Clay County, Baptist South, and Palatka
Patients 65 and older are the fastest growing segment of the US population By 2030, it will comprise 20% of the population There will be a disproportionate increase in patients greater than 75 years old Yancik R, Ries LA. Cancer in older persons: an international issue in an aging world. Semin Oncol 2004
There is a sharp rise in the incidence of most cancers after age 60 Currently 50% of all cancers arise in those 65 and older 70% of all cancer deaths occur in those 65 and older Yancik R, Ries LA. Cancer in older persons: an international issue in an aging world. Semin Oncol 2004
This age group is underrepresented in clinical trials Those that are included in trials result in data not applicable to the entire elderly population due to exclusions (esp over 80) Poor performance status Renal impairment Hepatic impairment Bone marrow dysfunction Scher KS, Hurria A. Under-representation of older adults in cancer registration trials: known problem, little progress. J Clin Oncol 2012
The essential principles of treating cancer in the elderly are the same as in younger patients NCCN Guidelines - Older Adult Oncology v. 1.2016 http://www.nccn.org/professionals/physician_gls/pdf/senior.pdf
Chemotherapy Radiation Surgery Alone or in combination/sequence
Challenges
Age related organ function decline Age-related loss of physiologic reserve Puts patients at risk for decompensation
Liver Decline in hepatic volume and blood flow Affects drug metabolism Liver metastases
Kidney Function GFR falls with age Loss of muscle mass complicates assessment Volume status
Bone marrow Reserve diminishes with age
Heart Increased risk of CAD Increased risk of valvular heart disease Decreased ventricular compliance
Muscle Sarcopenia - defined by loss of skeletal muscle mass two standard deviations below sex-specific normal values for young adults
Comorbdities DM Cardiac disease Anemia HTN GI dysfunction
Quality of life Available data suggest that older patients are just as willing to try chemotherapy as their younger counterparts, but less willing to endure severe treatment-related side effects Yellen SB, Cella DF, Leslie WT. Age and clinical decision making in oncology patients. J Natl Cancer Inst 1994 Sanoff HK, Goldberg RM, Pignone MP. A systematic review of the use of quality of life measures in colorectal cancer research with attention to outcomes in elderly patients. Clin Colorectal Cancer 2007
Pharmacokinetics
The aging process can significantly alter the pharmacokinetics of chemotherapy agents. These pharmacokinetic differences may be caused by alterations in excretion, metabolism, distribution and absorption.
Impaired renal function can result in higher peak drug levels and more prolonged exposure to chemotherapy, causing excessive toxicity with agents that are dependent upon renal excretion for their clearance Platinum agents Methotrexate
Heptic metabolism and function Although liver size and hepatic blood flow are decreased with aging, these changes are not of sufficient magnitude to require routine dose modification in elderly individuals. Concurrent hepatic impairment, due to the malignancy or other comorbid conditions, may necessitate dose adjustments. Adriamycin Gemcitabine
Functional Status
Chronologic age does not reliably predict physiologic decline. Dosing is not based on age. Modifications to doses or changes in therapy need to be considered when drug toxicity overlaps with comorbid conditions Increases susceptibility to complications
Relevant Comorbid Conditions CKD Hepatic disease Ascites/pleural effusion Decreased bone marrow reserve Heart disease ECOG PS > 2, KPS < 60
ECOG Performance Status Grade 0: Fully active, able to carry on all pre-disease performance without restriction Grade 1 : Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light house work, office work Grade 2 : Ambulatory and capable of all selfcare but unable to carry out any work activities. Up and about more than 50% of waking hours Grade 3 : Capable of only limited selfcare, confined to bed or chair more than 50% of waking hours Grade 4 : Completely disabled. Cannot carry on any selfcare. Totally confined to bed or chair Grade 5 : Dead -Oken MM, et al. Am J Clin Oncol 1982
Karnofsky Performance Status 100 - Normal; no complaints; no evidence of disease. 90 - Able to carry on normal activity; minor signs or symptoms of disease. 80 - Normal activity with effort; some signs or symptoms of disease. 70 - Cares for self; unable to carry on normal activity or to do active work. 60 - Requires occasional assistance, but is able to care for most of their personal needs. 50 - Requires considerable assistance and frequent medical care. 40 - Disabled; requires special care and assistance. 30 - Severely disabled; hospital admission is indicated although death not imminent. 20 - Very sick; hospital admission necessary; active supportive treatment necessary. 10 - Moribund; fatal processes progressing rapidly. 0 - Dead Karnofsky DA, et al. The Use of the Nitrogen Mustards in the Palliative Treatment of Carcinoma - with Particular Reference to Bronchogenic Carcinoma. Cancer. 1948
Cure What are the goals of therapy? ex. Early stage lung cancer Consider SBRT or chemo-rt instead of surgery Consider no adjuvant treatment for resected breast or colon cancer Disease Control Ex. CLL Palliation Consider oral biologic therapy instead of infused bio-chemotherapy Metastatic pancreatic cancer Consider single agent chemotherapy instead of multi-agent therapy
What are the patient s goals? Personal definition of quality of life The bucket list Trips Family events and milestones Etc.
Integrated Care In addition to multi-modality cancer therapy Nutrition Physical therapy Occupational therapy Aggressive pain management Psychosocial plan of care
Thank you Jeffrey A. Bubis, DO, FACOI, FACP Clay County, Baptist South, and Palatka jeffreybubis@csnf.us Cell 904-704-4170