A gradual diminution in the physiologic reserve or functional capacity over time is the characteristic hallmark of aging, and this has a direct impact on the choice of cancer therapy and its toxicity profile in elderly patients with cancer. With the expected rapid rise of the older population as a subgroup, oncologists will increasingly treat elderly patients. Provision of competent care to this increasing pool of older patients with cancer necessitates that oncology professionals become familiar with age-associated changes in organ physiology and their impact on cancer treatment and toxicity. In this comprehensive review, we have listed changes in cardiovascular, gastrointestinal, pulmonary, and renal physiology with aging. Also enumerated is the impact of these changes on cancer therapy and toxicity in each organ system-based section. Cardiovascular changes primarily lead to reduction of the cardiac functional reserve, with a consequent increase in the risk of congestive heart failure. Changes in gastrointestinal physiology lead to increased mucosal damage. A reduction in pulmonary reserve has implications for postradiation complications, and a decline in renal function leads to an increased potential for nephrotoxicity. These changes impair the ability of older patients with cancer to tolerate cancer therapy and increase their risk of toxicities. This may lead to an overall decline in functional status, resulting frailty, poor quality of life, and ultimately poor outcomes. Becoming familiar with age-related physiologic changes is the first step for oncologists seeking to better tailor their treatments. This, combined with adoption of some of the clinical interventions suggested in this review, can help better manage the geriatric oncology patient. Further research is necessary for the development of more specific evidence-based recommendations.
In this second article of our two-part review, we focus on age-associated physiologic changes involving the nervous, endocrine, hematologic, immune, and musculoskeletal systems, with close attention to the interconnected nature of these systems. There is a well-known connection between the neuroendocrine and immune systems via the hypothalamic-pituitary-adrenal axis and via interaction by means of cytokines, hormones, and neurotransmitters. These changes may lead to a loss of integration and resiliency with age, thus decreasing the ability of the elderly patient with cancer to adapt to stressful circumstances. Prominent changes include decline in memory and cognition, and increased susceptibility to peripheral neuropathy. Hematologic and immune changes like reduced bone marrow reserve and increased susceptibility to infections have far reaching implications for cancer care in the elderly. Gradual decline in hormone levels, and changes in muscle and body composition, can lead to functional decline and frailty. Use of the clinical interventions suggested in this article, along with an appreciation of the interplay of these age-related physiologic changes and their consequences, allows oncology professionals to customize therapy and minimize side effects in the geriatric oncology patient.
Background Alterations in the human epidermal growth factor receptor‐2 (HER2) pathway have been identified in a subset of salivary duct carcinomas. Dual HER2 inhibition with trastuzumab and pertuzumab has superior antitumor efficacy to trastuzumab monotherapy in HER2‐positive breast cancer, yet its efficacy in HER2‐positive salivary duct carcinoma is unknown. Methods We report 2 cases of exceptional responses of HER2‐positive salivary duct carcinomas to dual HER2 blockade and docetaxel combination and their molecular characteristics. Results A 54‐year‐old man with recurrent metastatic HER2 expressing salivary duct carcinoma of the parotid gland after definitive concurrent chemoradiation achieved a complete response (CR) after 6 cycles of trastuzumab, pertuzumab, and docetaxel (TPH). A 42‐year‐old woman with HER2‐positive salivary duct carcinoma of the parotid gland with bone and liver metastases had CR with TPH and remains in remission on maintenance trastuzumab and pertuzumab. Conclusion Dual HER2 blockage resulted in CR in patients with HER expressing salivary duct carcinoma and warrants further evaluation in this patient population.
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