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Chemotherapy dosing in older adults with cancer: One size does NOT fit all

Published:August 24, 2022DOI:https://doi.org/10.1016/j.jgo.2022.08.012
      Cancer is a disease of aging with nearly 60% of all cancer diagnoses and 70% of all cancer deaths occurring among older adults over the age of 65 years [
      National Cancer Institute Surveillance Epidemiology and End Results Program. Cancer Stat Facts.
      ]. Older adults with cancer continue to be underrepresented in cancer clinical trials resulting in significant knowledge gaps regarding the management of older adults with cancer, including how to adapt and personalize conventional treatment strategies for older patients [
      • Hurria A.
      • Levit L.A.
      • Dale W.
      • et al.
      Improving the evidence base for treating older adults with cancer: American Society of Clinical Oncology Statement.
      ]. Severe and potentially life-threatening chemotherapy toxicities remain common in older adults with advanced cancer, as approximately over half of older patients experience grade 3–5 chemotherapy toxicities [
      • Extermann M.
      • Boler I.
      • Reich R.R.
      • et al.
      Predicting the risk of chemotherapy toxicity in older patients: the chemotherapy risk assessment scale for high-age patients (CRASH) score.
      ,
      • Hurria A.
      • Togawa K.
      • Mohile S.G.
      • et al.
      Predicting chemotherapy toxicity in older adults with cancer: a prospective multicenter study.
      ]. Recent evidence has shown that for older adults deemed “unfit” for standard chemotherapy, upfront dose modification resulted in improved tolerance and health-related quality of life (HRQoL), while maintaining efficacy. For example, the GO2 phase III trial of older adults with advanced gastroesophageal cancer treated at 3 dose levels of capecitabine + oxaliplatin (full dose, 80% dose, 60% dose) found that the lowest dose level (60% dose) resulted in the best treatment outcomes, even in younger, less frail patients [
      • Hall P.S.
      • Swinson D.
      • Cairns D.A.
      • et al.
      Efficacy of reduced-intensity chemotherapy with oxaliplatin and capecitabine on quality of life and cancer control among older and frail patients with advanced gastroesophageal cancer: the GO2 phase 3 randomized clinical trial.
      ]. This approach is consistent with the “start low and go slow” dosing axiom that is a mantra of the field of geriatrics. In addition, a seminal study of a geriatric assessment-based intervention prior to chemotherapy resulted in frequent upfront dose reductions, which resulted in less chemotherapy toxicities, better HRQoL, and similar survival [
      • Mohile S.G.
      • Mohamed M.R.
      • Xu H.
      • et al.
      Evaluation of geriatric assessment and management on the toxic effects of cancer treatment (GAP70+): a cluster-randomised study.
      ]. However, other recent studies of geriatric assessment-based interventions conducted primarily after the initiation of chemotherapy and focused on aging-related interventions to improve HRQoL showed no effect, suggesting that a large portion of the benefit of undergoing a geriatric assessment is to identify patients at risk of severe toxicities and to provide upfront dose modification [
      • Puts M.
      • Alqurini N.
      • Strohschein F.
      • et al.
      Comprehensive geriatric assessment and management for Canadian elders with cancer: The 5C study.
      ].

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