The normal physiological changes of aging and their impact on the response to cancer treatment

The Normal Physiological Changes of Aging and Their Impact on the Response to Cancer Treatment Karen Smith Blesch

P

HYSIOLOGICAL AGING is characterizedby gradual but significant changesin body structure, composition, and functioning’ that result in a diminished capacity to respond to and recover from stress.2 Changes in some systems impose stresson other systems. For example, changesin body composition that alter the pharmacokinetics of certain drugs may result in a greater load on the liver and kidneys as the drugs are metabolized and excreted. Structural changes in vasculature may alter the perfusion and function of vital organs. Decline in physiological functions that require the integration of multiple structures and systemsmay have a more significant impact on the individual’s ability to maintain homeostasis than changes in single organs, tissues, or cells.3T4 Historically, elderly cancer patients have not been treated as aggressivelyas their younger counterparts becauseit was felt that they would not be able to adapt to and tolerate the multiorgan, multisystem stressesimposed by aggressive surgery, radiation therapy, and in particular, chemotherapy. This trend is changing, however, and today many older cancer patients receive aggressivetreatment for their disease. It is important for oncology nurses to understand cancer treatment approaches in the elderly and to be familiar with the normal physiological changes of aging that may affect their patients’ responsesto treatment, in order to provide optimal care to this growing segment of the population.

as well as among organs and systems,and may be influenced by factors such as nutrition, lifestyle, or the presenceor absenceof chronic disease. It is important to remember that while the age of 65 serves well as an operational definition of elderly for epidemiological or other studies, it is not a valid indicator of an individual’s physiological functioning or reserve.’ The changesdiscussedbelow occur in the general population and should be appropriately evaluated in each individual as cancer treatment is considered. Changes in Physiological Functioning

For the most part, decline in physiological function begins just after maturity and continues in a linear fashion through the eighth and ninth decades. There is no “plateau” during the middle years in which prime physiological capacities are maintained.* Figure 1 illustrates the linear decline of several physiological parameters.In addition to alterations in cardiac index, vital capacity, glomerular filtration, renal plasma flow, and breathing capacity, hepatic blood flow is reduced,’ and there is evidence of decreasedhematopoietic reserve.’

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NORMAL PHYSIOLOGICAL AGING

Although the specific relationship of aging per se to the changes commonly seen in an elderly population has yet to be determined,536there is no question that specific alterations occur. These changesexhibit great variability among individuals From Rush-Presbyterian St Luke’s Medical Center, Chicago. Address reprint requests to Karen Smith Blesch, MS, RN, 2027 Sherwood Place, Wheaton, IL 60187. 0 1988 by Grune & Stratton, Inc. 0749-2081188lO403-0003$05.0010

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20 Fig 1. Effect of advancing age on normative changes in physiological functions. Reproduced with permission (Rowe JW, Bradley EC: The elderly cancer patient: Pathophysiological considerations, in Yancik R ted): Pemfbctives on Prevention and Treatment of Cancer in the Elderly. New York, Reven, 1983).

Seminars in On.cology Nursing, Vol 4, No 3 (AugustI,

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IMPACT

OF PHYSIOLOGICAL

CHANGES

ON TREATMENT

Changes in Body Composition and Structure

Changes in body composition also occur as an individual ages. There is an overall decreasein lean body mass,whereasfat masstends to increase until late middle age” and may begin to decrease after age 65.5 The net effect of thesechangesis an increase in the fat/lean body massratio. Additionally, total body water decreasesas does serum albumin. These changes, along with decreasesin glomerular filtration and vital organ perfusion, have significant pharmacokinetic implications.“*‘* In addition to loss of bone, muscle, and vital organ mass, other structural changes occur with age. Most tissuesdevelop progressivestiffness and rigidity, which contribute to increased peripheral resistanceto blood flow as well as inhibition of the passageof substancesfrom the blood into various organs.6 The skin undergoessignificant structural changes as well, with a decreasein subcutaneous fat and a thinning of the epidermis and dermis. The dermis loses elasticity and turgor, which decreases its effectiveness as a structural and vascular support.l3 Table 1 summarizes the physiological and metabolic changesof aging. RESPONSE TO CANCER TREATMENT

Regardless of age, an individual’s responseto any form of treatment for any diseaseis dependent upon the therapeutic index of the treatment, that is, upon the relationship between the therapeutic and the toxic effects of the treatment. When a treatment is highly effective and only slightly toxic, the therapeutic index is high; conversely, a toxic treatment that is only occasionally effective has a low Table 1. Physiological

and Metabolic

Changes

of Aging

Body Composition Increased adipose tissue Decreased protein and water Liver Decreased hepatic blood flow Decreased ability to activate carcinogens and drugs Decreased ability to conjugate drugs Increased ability to deactivate carcinogens Kidney Decreased glomerular filtration rate Decreased renal blood flow Hematopoetic system Decreased hematopoetic stem cell reserve Reprinted

with permission.’

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therapeutic index. Certain forms of cancer therapy have a lower therapeutic index than treatment for nonmalignant conditions. The therapeutic index of many drugs for nonmalignant conditions is lower in the elderly.12314Major surgery is also considered to carry more risk.15,16Thus, one might expect that the low therapeutic index of many cancer treatments might be lowered even further when used in the elderly. Important conceptsto consider when caring for elderly patients receiving cancer treatment are summarized in Table 2. Surgery

Surgery is the main treatment for many solid tumors and often is the sole form of therapy received by elderly individuals with cancer17,18 Cancer surgery imposes major physiological stress, disrupting multiple organs and systems that may already be compromised as a result of aging. Integrity of the skin, a critical protective barrier, is interrupted. Blood and body fluid pathways may be interrupted, further compromising peripheral circulation and perfusion of vital organs as well as promoting stasis of unwanted fluids. Stress is placed on the cardiopulmonary system. Reduced renal function may result in difficulty maintaining delicate fluid and electrolyte balances. Malnutrition and the cancer diseaseprocess itself may result in prolonged, and suboptimal healing.” The elderly cancer patient’s risk for surgical morbidity and mortality can be minimized, however, if there is careful preoperative evaluation and preparation, meticulous and judicious surgical technique, and comprehensive postoperative care.*’ Preoperative evaluation includes a thorough assessmentof cardiovascular, renal, pulmonary, and hepatic function as well as nutritional, mental, and psychosocial status. In addition, the tumor should be carefully evaluated for its potential resectability and any distant metastases*’since the stageof cancer at diagnosis varies with the age of the patient. 17718Y21 Richards16 identifies three factors that must be considered when contemplating cancer surgery in the elderly: the patient’s life expectancy and general physiological condition as they are affected by concomitant disease processes, the availability of effective nonsurgical treatment, and the surgical procedure’s therapeutic index. Once surgery is decided upon, careful patient preparation that includes correction of underlying

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Table 2. Important Concepts to Consider When Caring for the Elderly Individual With Cancer Surgery Preoperative assessment and correction of underlying physiological abnormalities Vigorous pulmonary hygiene Early, comprehensive discharge planning Early identification and correction of postoperative complications Resumption of preoperative routines and environment as soon as possible Use of family/friends for support and assistance Radiation Therapy Radiation may be used as an alternative to surgery. Radiation may have curative or palliative intent. Modifications in the treatment plan may minimize toxicity without compromising the outcome. The integrity of the skin, mucous membranes, and bone marrow may be compromised before Comprehensive physiological and psychosocial supports are imperative.

radiation

therapy

begins.

Chemotherapy Individual physiological and psychosocial circumstances are more important than chronological age in predicting treatment outcomes. Scrupulous assessment and monitoring of appropriate physiological parameters is critical to preventing toxicity. The normal physiological changes of aging may affect the pharmacodynamics of various agents making them more or less effective/toxic. Hormones Hormones may predispose the elderly cancer patient to a variety of cardiovascular and metabolic disorders. Antiemetics The antidopinergic and anticholinergic effects of most antiemetics present a greater risk to the elderly patient than to younger individuals for confusion, sedation, and metabolic and cardiovascular dysfunction. Antibiotics Underlying conditions such as renal and hepatic dysfunction, or malnutrition make the elderly cancer patient very susceptible to serious adverse effects of antibiotics. Analgesics NSAlDs can produce a wide variety of undesirable effects in the elderly, necessitating extreme care in their use. Regular use of acetaminophen in therapeutic doses can be hepatotoxic in the elderly. Narcotic analgesics, used in the presence of dehydration, can produce hypotension and severe constipation.

conditions such as congestive heart failure, fluid and electrolyte imbalances, or malnutrition is essential. Skin preparation should be performed with caution to prevent infection and unnecessaryirritation. Preoperative teaching and implementation of vigorous pulmonary toilet are essentia1.20’22 Discharge planning should also begin at this early stage. Intraoperatively, surgical technique may be modified from more traditional surgical approaches to include less radical removal of diseasedtissue and narrower tumor margins in order to leave as much normal tissue as possible.*’ Postoperatively, the elderly patient is particularly at risk for developing hypotension, hypothermia, respiratory complications, thrombophlebitis, thromboembolism, renal failure, delerium, urinary tract infection, and fluid and electrolyte imbalances.23 These complications can be prevented with prompt identification and correction of physiological abnormalities, early mobilization, good pulmonary toilet, and resumption of presurgical routines as quickly as possible. Pain medica-

tions and others should be used in a judicious and effective manner. Intravenous (IV) and nasogastric tubing can hamper mobility, and gastrostomy and central venous accessshould be considered if longterm drainage or IV nutritional support are anticipated. Dellefield ** has identified some specific nursing activities to enhancethe elderly cancer patient’s recovery from surgery. The elderly patient may be discharged from the acute care setting earlier than has been the custom, not only becausechangesin the health care system mandateit,24 but becauseit may be in the patient’s best interest .25 Thus, aggressive, sophisticated nursing care must be continued after hospitalization through comprehensive discharge planning, patient and family education, and extended care in another institution if necessary,or at home. With careful planning, techniques, and followup, surgery is a viable intervention for elderly cancer patients. Nonetheless, it is a major stressor, and the patient will require sophisticated physiological and emotional care and support in order to regain and maintain normal functioning.

IMPACT OF PHYSIOLOGICAL CHANGES ON TREATMENT

Radiation Therapy

Radiation therapy is widely used as both a curative and palliative treatment modality for many cancers in the elderly. Curative radiation therapy may be used in prostate, colorectal, skin, lung, breast, and gynecologic cancers, with the goal of eradicating diseasethat is local, or at most regional in character. In an elderly cancer patient, curative radiation therapy may be chosen over surgery when both treatment modalities carry an equal prognosis for long-term survival. Curative radiation therapy, when appropriately applied, may impose less physiological stress on the individual than major surgery.26 Palliative radiation therapy may be indicated for a variety of symptomsrelated to advanceddisease including pain from bony metastases;obstructed airways and lumens; compressionof vascular, neurological, and lymphatic pathways; hemorrhage; and symptomsrelated to tumor bulk. Palliative radiation therapy should be delivered in such a manner that it does not produce complications but results in an improved quality of life for the patient. 26 Current levels of sophistication in the delivery of radiation therapy allow for a more favorable therapeutic index in both palliative and curative approaches.Advances in technology for administration of external beam, local brachytherapy, and systemic therapy provide the therapist with a variety of choices in determining the most appropriate approach for the elderly patient. Although it does not appear that tumors in the elderly require less radiation than tumors in younger individuals for a therapeutic effect,27 modifications in fractionation, dosimetry, protraction of therapy, and the areabeing treated can minimize potential toxicities and side effects.26 Gunn,27*28for example, has proposed a “split course” of radiation therapy for elderly patients in which a “standard” radiation therapy regimen is broken into two or more shorter courses with rest periods ranging from 2 to 3 weeks to 2 or 3 months interspersedthroughout the course. Brady and Markow,26 on the other hand, emphasize the radiation therapy should not be “interrupted” unless absolutely necessary. They suggest the alteration of fractionation and treatment schedules to minimize side effects but not compromisethe potential for long-term tumor control. This may include a short, intensive course of radiation therapy for a fast-growing tumor in

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which there is a short life expectancy, or lowered doses extended over a longer period of time for slow-growing diseasein which life expectancy is longer. While the suggestionsof these authors are significant, they are basedon clinical evidence and experience, rather than on carefully controlled investigations. The elderly cancer patient should be treated in a setting where the radiation oncologist has significant expertise in treating patients of similar age with similar tumors. State of the art technology and application techniques for radiation therapy should be available. The tumor should be carefully evaluatedfor a curative or palliative approach, and the patient’s general health and psychosocial situation must be considered. A comprehensive plan including physiological, nutritional, and psychosocial supports should be developed and implemented by a multidisciplinary team. Although various manipulations described above may enhancethe therapeutic index of radiation therapy in the elderly patient, radiation remains a major stress, with potential for creating multiple problems, both physiological and psychological. The skin and mucous membranesare very susceptibleto radiation damage,and their ability to tolerate and repair radiation damagemay be comleading to a high risk for promised in old age,22929 infection. Reducedbone marrow reserve,’ perhaps already compromised by previous or concomitant chemotherapy, may not be able to recover adequately from radiation exposure, leading to anemia, neutropenia, and thrombocytopenia. Fatigue, infection, and the potential for seriousbleeding are possibilities and should be anticipated. Psychosocialsupports are imperative. Radiation therapy frequently necessitatesdaily trips to the hospital or clinic for treatment, and safe, adequate transportation is a must. Changesin oral and gastrointestinal (GI) mucosaand function,** anorexia, and perhaps cachexia” may result in nutritional requirements3’that the elderly person cannot meet without help. Fatigue may result in multiple selfcare deficits necessitatingassistancewith personal care, as well as homemaking and other domestic activities. Emotional support is also essential. While psychosocial support is often available from family membersand/or significant others, this may not be the case for all individuals. Each elderly cancer patient’s psychosocial support system should be individually evaluated. Community resourcesneed to be assessedand utilized as we11.25

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Chemotherapy

Chemotherapy has traditionally been withheld from the elderly or administered in reduced doses, but has now become a major focus of attention in geriatric oncology. The classic study by Bonadonna and Valagussa,31 which suggested that lower doses of adjuvant chemotherapy for breast cancer in older women may have worsened their treatment outcomes, perhapsprovided the impetus for the increased interest in this treatment modality. Given the overall decline in physiological reservesthat typifies older populations, it is not surprising that chemotherapy, with its profound toxicities and low therapeutic index, was not considered a viable treatment alternative until recently. Like surgery and radiation therapy, it has becomeapparentthat chemotherapy, when administered in careful consideration of the individual’s diseaseand physiological status, may be a useful treatment alternative for the elderly cancerpatient. Two retrospective studies, based on data collected by the EasternCooperative Oncology Group (ECOG),32*33attempted to identify the incidence and severity of toxic effects of cancer chemotherapy in elderly patients. Begg et a132were unable to identify any statistically significant increasesin the severity or frequency of chemotherapytoxicity in a series of 2,981 patients with advanced breast, lung, or colorectal cancer. All patients had normal renal, hepatic, and cardiovascular function, and only minor or nonexistent comorbidities . Another study33analyzed toxicity data from 6,239 patients in 19 studies of chemotherapyfor advancedcancer in eight major organ sites. A similar frequency of and severity of toxic reactions was found among patients >70 years of age and their younger counterparts, except for an increased incidence of hematologic side effects for older patients being treated for head and neck tumor, ovarian and gastric malignancies, melanoma, and sarcoma.Methotrexate and methyl semustine(CCNU) were identified as the culprits in producing age-related hematologic toxicities, and reduced renal clearance of methotrexate may have contributed to its toxicity. Although the aforementionedstudiesprovide interesting data, their clinical usefulnessis limited in that the individuals selected for participation may be generally healthier than elderly cancer patients at large. Furthermore, while there was little signif-

icant difference in frequency and severity of toxicity between younger and older patients, it remains that severe toxicity does occur in both age groups. The elderly patient’s ability to tolerate and recover from severe toxicity was not addressed. Since aging is characterizedby a diminished ability to maintain and regain homeostasisin the presenceof physiological stress(ie, chemotherapytoxicity), this is a significant issuethat may ultimately determine the patient’s treatment outcome. The studies do demonstrate, however, the importance of thorough, individualized evaluation of all physiological parameters to enhance treatment outcomes. Other studiesof elderly cancerpatients have had variable results. In one study, there was significant morbidity and mortality among elderly patients being treated for histiocytic lymphoma using the CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) regimen.34 The authors suggested that more aggressive supportive care (eg, antibiotics) might have improved treatment outcomes. Dixon et a135documented decreasedsurvival in elderly lymphoma patients. Cohen et a136 reported that elderly patients with multiple myeloma, treated with carmustine (BCNU), cyclophosphamide, and prednisone on a Southeastern Cancer Study Group protocol had tumor responses and incidence of toxic effects similar to their younger cohorts. They concluded that elderly multiple myeloma patients could respond to and tolerate chemotherapyat least as well as younger individuals. Another study, a retrospective chart audit of 24 patients over the age of 70 receiving a variety of combination chemotherapy regimens for small cell carcinoma of the lung, concluded that patients >70 years benefitted from combination chemotherapy without excessive toxicity.37 Ninety-two percent of the individuals in this study had at least one other serious chronic disorder such as heart disease or renal failure-and perhaps were more representative of elderly patients seen in general oncology practice. It is interesting to note, however, that dosagereductions were made for at least 30% of the patients. The difficulties inherent in studying the effects of chemotherapyin the elderly are many. The great variety of treatment protocols studied makesit difficult to identify specific trends. Combination chemotherapy further complicates attempts to obtain information about specific agents. There is a

IMPACT

OF PHYSIOLOGICAL

CHANGES

dearth of prospective, well-controlled studies examining specific treatments for specific tumors. Although clinical reports provide practical clinical information, the information they contain may be skewedby missing data, lack of standardizedtreatment approaches,or concurrent medical problems. Finally, many oncologists may not be willing to report unfavorable results with aggressivechemotherapy in uncontrolled studies, and many journals will not publish such data. Little is known about the impact of the normal physiological changes of aging on the pharmacodynamics and pharmacokinetics of chemotherapeutic agents. Kelly3* has speculatedon the pharmacodynamicsof various chemotherapeuticagents based on what is known about their distribution and metabolism. For example, drugs that are activated by the liver may have a decreasedtherapeutic effect in the presenceof decreasedliver funcTable 3. Potential Normal Changes GI tract38-40 T Gastric pH J Splanchnic blood flow 1 Absorptive surface & GI motility Body Composition3s t Fat/lean ratio J Lean mass 1 Total body water -1 Albumin t Globulin Hepatic functionas 1 Hepatic mass J Hepatic blood flow -1 Enzyme activity

Effects of Aging

tion, and drugs that are excreted via the kidneys may show increasedtoxicity with a decline in renal function. The anticipated effects of aging on specific drugs are summarized in Table 3. Organ-specific toxicities of chemotherapy are another area of concern in elderly cancer patients. In a prospective study of cisplatin, Hrushesky et a139failed to find age-dependentcisplatin nephrotoxicity as measuredby serial 24-hour creatinine clearances. This study contradicts a widely held assumptionthat cisplatin may be more nephrotoxic in the elderly because of diminished renal function. On the other hand, Van Hoff et a141reported an increased incidence of cardiomyopathy in elderly patients receiving doxorubicin. Myelosuppressionis a major concern with many cytotoxic agents, and aged bone marrow may be more susceptible to the myelotoxic effects of chemotherapy.31Gelman and Taylor,42 however,

on the Pharmacodynamics

of Various

Absorption GI tract

6-mercaptopurine’ Hexamethylmelamine” Melphalan*

via

Distribution of fatsoluble drugs

Protein-binding

Activation by liver

Chemotherapeutic

of drugs

of drug

of drug

k Clearance of renally excreted drugs

Agents Anticipated Effect

Agents

Aifected Mechanism

Inactivation by liver

Renal function3* J Glomerular filtration J Renal blood flow 4 Tubular function

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ON TREATMENT

Variable

BCNU CCNU Methyl-CCNU Procarbazine Cisplatin

t Volume of drug distributed

Cyclophosphamide Prednisone Hexamethylmelamine DTIC Daunorubicin Doxorubicin Vincristine Vinblastine

Less drug available for therapeutic effect

Methotrexate Cisplatin (?)a9 Bleomycin Hydroxyurea Mithramycin Streptozocin Cyclophosphamide

More drug available for therapeutic/toxic effect

* The absorption of most categories of orally administered drugs is not thought GI tract. These three drugs are known to vary in their absorption.

to be significantly

t Free fraction of drug available for therapeutic (or toxic) effect

Increased

altered

toxicity

by changes

in the aging

KAREN SMITH

184

adjusted doses of cyclophosphamide and methotrexate to patients’ individual creatinine clearance rates and found reduced myelotoxicity. They hypothesized that exaggerated myelotoxicity in the elderly may be due to the drugs’ not being cleared as efficiently rather than their direct effect on the bone marrow, a supposition compatible with the ECOG studies discussed previously. To date, no studies have addressedthe elderly patient’s ability to recover from myelosuppressionregardlessof its incidence, severity, or source. From data currently available, it is not clear whether older individuals differ from younger individuals in tumor responsiveness or drug tolerance.40 It seemsreasonablethat the aging of vital organs and functions such as hearing may enhance the clinical manifestations of chemotherapy end-organ toxicity, but more thorough investigations are needed. It has been suggestedthat an individual’s performance status is the most important predictor of responseto chemotherapy.7Patients who are bedridden more than 50% of the time are probably poor candidates for aggressive treatment, unless their deterioration is due to an aggressive but highly responsive malignancy such as acute leukemia. Cohen43notes that although chemotherapyis successful in many situations, regardless of age, there are times when it is of little benefit in metastatic disease.He suggeststhat the benefits of chemotherapy be critically evaluated and weighed against the risks to quality and quantity of life, and cautions clinicians to consider the potential for poor treatment outcomeswhen elderly patients are treated as aggressively as younger ones. Hormones

Hormones are another form of cancer therapy usedfrequently in the elderly population. They can be of significant benefit to patients with advanced cancers of the breast, prostate, endometrium, and hematologic neoplasms.44 Hormone-dependent breast cancersrespond more favorably to estrogen (diethylstilbestrol) therapy in postmenopausal women than in premenopausalor perimenopausal women. The incidence and severity of adverseeffects (nausea,vomiting, anorexia, breast engorgement) decline in older women, but the incidence of fluid retention increases.44 Estrogen may also be used to treat carcinoma of the prostate, although cardiovascular complications such as thrombophlebitis, congestive heart

BLESCH

failure, and cerebral vascular accident are known to occur, and may be fata1.45Pre-existing cardiovascular diseaseappearsto contribute to morbidity and mortality. Careful cardiovascular monitoring and perhaps dosage reductions may decreasethe probability of severe complications.44 Corticosteroids are employed in breast, prostate, and hematologic neoplasms. They may activate a pre-existing subclinical diabetic state, or produce osteoporosiswith long-term use. Sodium and fluid retention may also be a problem with these agents. The elderly patient receiving corticosteroids requires careful observation and monitoring of serum glucose levels, mental status, musculoskeletal integrity, and cardiovascular status.44 SUPPORTIVE CARE CONSIDERATIONS ELDERLY CANCER PATIENT

FOR THE

Protective Mechanisms

Altered protective mechanismsshould be the focus of nursing care for the elderly cancer patient, regardlessof the treatment modality. The surgical patient’s protective mechanismsare severely compromised. Disruption of normal anatomic barriers, creation of dead space, removal of lymphatic tissue, and fluid accumulation and stasis all predispose the surgical patient to life-threatening infection. The skin, mucous membranes, and hematopoietic systemsmay be major problem areas with radiation therapy. Hematologic toxicity and potential infections are major concernsfor the elderly patient receiving chemotherapy. The skin may be at a risk for damagefrom vesicant chemotherapeutic agents. The central and peripheral nervous systemsare also important protective mechanisms that can be compromised by treatment modalities or the diseaseprocess. Protective mechanismsdo not operate in isolation. Nutritional deficits (secondary to nausea, vomiting, anorexia, or cachexia) lead to a diminished supply of protein and energy available for maintenance and repair of skin, mucous membranes, muscle, and antibodies. Pain interferes with mobility. Immobility secondary to pain or weakness predisposes the patient to skin breakdown, decreased tissue perfusion, and venous, fluid, and secretion stasis. Less than optimal airway clearance from lung disease, normal aging process, and/or treatment-induced fibrosis set the stagefor pneumonia. Alterations in urinary elimination due to surgery or catheterization predispose

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OF PHYSIOLOGICAL

CHANGES

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ON TREATMENT

the patient to invasion of microorganisms. Vannicola29 has developed an extensive plan of nursing interventions for the assessmentand management of altered protective mechanisms in the elderly cancer patient. Many of today’s approachesto managing adverse responsesto cancer treatment involve extensive use of medications. Antiemetics, analgesics, and antibiotics are potent agentsthat are most commonly used to “support” cancer patients during treatment. Their use should not be taken lightly at any age, but this is particularly true in the elderly. Antiemetics The most commonly used antiemetics include prochlorperazine, tiethylperazine, trimethobenzamide, and more recently, transdermal scopolamine. Metaclopramide, diphenhydramine, lorazepam, and dexamethasone are additional agents that are used alone or in a variety of combinations . Prochlorperazine, tiethylperazine, trimethobenzamide, and metaclopramide are thought to exert their antiemetic effect by blocking dopamine uptake in the chemoreceptortrigger zone in the central nervous system. Dopamine blockade may result in extrapyramidal reactions, hypotension, and sedation, all of which may be more prominent in the elderly.46 Metaclopramide has been shown to significantly decreaserenal plasma flow, perhaps by its antidopamine activity.47 The anticholinergic side effects of prochlorperazine and transdermal scopolamine (confusion, disorientation, blurred vision, cardiac complications, constipation, thickened respiratory and oral secretions, urinary retention) present a greater risk to compromised elderly patients.46Lorazepamhas a short half-life in the elderly and does not have any known major adverse effects or drug interactions,46’48although it may produce sedation. Diphenhydramine is also consideredsafe, but sedating.46 Dexamethasone may reduce glucose tolerance, enhance sodium and water retention, and accentuatepotassiumloss in patients receiving diuretics.46 Antibiotics The elderly cancer patient may receive a variety of antibiotic agents for specific infections or prophylactically. The vast number of agentsusedpro-

hibits an in-depth examination of their specific effects, and the reader is referred elsewhere for information on specific agents and their use and actions in elderly individuals.46*49350 Elderly patients at risk for adverse effects from antibiotics include those with a history of allergy, or with hepatic or renal insufficiency. Broadspectrum antibiotics eliminate normal gut flora as well aspathogens.Diarrhea, the usual result of this effect, may be a significant problem when chronic illness and malnutrition are present. In addition, vitamin K synthesis, which is dependenton normal gut flora, may be compromised, precipitating serious coagulation abnormalities.46 Careful assessmentsof renal, hepatic, and nutritional status are imperative. Agents should be selected carefully and serum levels (especially of aminoglycosides) monitored. Drug-drug interactions should be considered and avoided. Table 4 identifies various categoriesof antibiotics and considerations for their use in the elderly. Analgesics Pain relief is of major importance. Pain may be acuteor chronic, and medication is usually the first line of defense. As with other medications, there are specific considerations for using analgesics in elderly cancer patients. Analgesics are categorized as narcotic or nonnarcotic, with nonnarcotics including acetaminophen and nonsteroidal antiinflammatory drugs (NSAIDs). The NSAIDs include aspirin, ibuprofen, naproxen, indomethacin, sulindac, tolmetin, and piroxicam. These drugs are widely used in the elderly population for analgesia, rheumatologic disorders, and a variety of miscellaneouspurposes.46 The NSAIDs are gaining popularity for treatment of cancer pain. Serious adverseeffects of NSAIDs in the elderly have been reported51including phototoxicity, liver failure, headache,confusion, and gastrointestinal side effects. Sodium and fluid retention have also been a problem. As experience is gained with the use of these drugs it is apparent that some NSAIDs pose more problems in the elderly than in others. On the other hand, when one NSAID does not achieve the desired effect, another may.46 The use of NSAIDs in the elderly cancer patient should be undertaken with careful evaluation of the patient’s needs, physiological status, and a thorough understanding of the pharmacokinetics of the agent being considered.

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Table 4. Antibiotic Categories and Potential Adverse Effects in the Elderly Cafecow Penicillins

Cephalosporins TrimethoprimSulfamethoxazole (Bactrim, Septra) Aminoglycosides

Tetracyclines Chloramphenicol Erythromycin Vancomycin Clindamycin

Comments

Generally safe unless history of allergy/anaphylaxis; sodium and fluid retention, hyperkalemia may occur; neurotoxicity (ticaricillin, carbenicillin); diarrhea, psuedomembranous colitis. Dosage reductions may be necessary if renal function is impaired. Relatively safe; side effects and activity similar to penicillins; cross-sensitivity to penicillins in 10% to 15%. Reduce dosage in renal failure or creatinine clearance ~25 mUmin; use with caution in malnutrition or malabsorption (blood dyscrasias may result); skin rash; GI upset; potential interaction with oral hypoglycemics or anticoagulants. Renally excreted; ototoxic; nephrotoxic; interfere with neuromuscular transmission; correct dosage varies among patients; monitor serum peak and trough levels on days 1 and 4 and periodically throughout therapy; ototoxicity may be potentiated when used with furosemide or ethacrynic acid. Broad spectrum; toxic to kidney and liver; do not use in renal failure; rarely antibiotic of first choice for elderly patients unless sensitive to other antibiotics. Broad spectrum; high CNS penetration; can cause bone marrow suppression (anemia); stomatitis; diarrhea; oral candidiasis; neurotoxicity may occur. Spectrum includes most gram-positive organisms; GI upset with oral preparations; vein irritation, thrombophlebitis with IV preparations. Narrow spectrum (gram-positive cocci and bacilli); renally excreted (reduce dose in renal insufficiency); ototoxic, nephrotoxic. Spectrum includes anaerobes and some aerobic gram-positive organisms; pseudomembranous colitis is major toxicity-discontinue if diarrhea develops.

Data from SloarY’c and Fox.~’ Abbreviation: CNS, central nervous

system.

Acetaminophen can have significant hepatotoxicity, and this is its major drawback for use in the elderly. Hepatotoxicity can occur with regular use of 2.6 g/d or less, if there is preexisting liver dysfunction. Dosagesabove 650 mg, four times daily are not recommended. Acetaminophen may be combined with a narcotic for enhancedpain relief with reduced toxicity.46 Elderly patients receiving narcotics for severe

cancerpain may develop hypotension, particularly if their fluid volume is depleted or there is cardiovascular insufficiency. Patients with underlying pulmonary diseasemay be more susceptibleto respiratory depression.Cognitive dysfunction may be aggravatedand chronic constipation may worsen, leading to fecal impaction, colonic dilatation, and obstruction. Table 5 summarizes specific considerations for narcotic analgesics.46

Table 5. Consideretions for Use of Various Narcotic Analgesics in the Elderly Comments

Drug

Morphine Meperidine

Propoxyphene Codeine Levorphanol Hydromorphone Methadone

Data from Sloan.46 Abbreviations: CNS, central

Oral form undergoes extensive metabolism in the liver, therefore, t bioavailability in liver dysfunction; usually well tolerated; duration of action may be increased in liver dysfunction. Lower incidence of GI side effects (nausea, vomiting, constipation) than morphine; increased CNS side effects; extensive hepatic metabolism may alter effectiveness, duration of action in liver dysfunction. Narcotic derivative; weak analgesic properties; can be highly toxic in large quantities or when taken with alcohol. Good oral efficacy; may be used as antitussive; best analgesia when combined with aspirin or acetaminophen; not well tolerated in doses high enough to approximate morphine analgesia. High potency; excellent oral efficacy; side effects similar to other narcotics. High potency; excellent oral efficacy; 4 mg hydromorphone IM equivalent to 27 mg morphine IM; suppository available for more sustained release. Better oral efficacy than morphine; significantly longer duration of action may lead to accumulation of drug with repeated doses.

nervous

system;

IM, intramuscular.

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IMPACT OF PHYSIOLOGICAL CHANGES ON TREATMENT

CONCLUSION

The elderly cancer patient presents complex problems and needs comprehensive physiological and psychosocial support in order to maintain homeostasis under the stress of the disease and its treatment. Many of the supportive measuresused involve polypharmacy, and drug-drug interactions may further tax the individual’s physiological reserves, producing unwanted effects. It is clear that

there is much need for researchinto various issues in geriatric oncology, and that the numbers of elderly cancer patients will continue to grow. For now, optimum treatment involves thorough, individualized physiological and psychosocial assessment of the patient, his disease,and the anticipated treatment outcome, as well as management and evaluation of therapeutic and supportive interventions .

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