Comprehensive Review

Supportive Care of Elderly Patients with CancerLodovico Balducci

Key words: Geriatric assessment, Nausea, Opioids, Pain management, Prophylactic treatment

Abstract

The majority of cancers are more prevalent in individuals aged ≥ 65 years than in younger patients, and supportive care is the key totreatment tolerance and quality of life for these individuals. This article examines the management of common complications ofchemotherapy and pain in older patients with cancer. In accordance with the National Cancer Center Network guidelines, it isrecommended that individuals aged ≥ 65 years be treated prophylactically with filgrastim or pegfilgrastim for the prevention ofneutropenic infections when challenged by chemotherapy of dose intensity comparable to that of CHOP (cyclophosphamide/doxorubicin/vincristine/prednisone) and that the levels of circulating hemoglobin be kept at ≥ 12 g/dL. In addition, it is recommendedthat the dose of cytotoxic agents be adjusted to renal function and that low-toxicity treatment (ie, capecitabine in lieu of 5-fluorouracil[5-FU], pegylated liposomal doxorubicin in lieu of doxorubicin) be used when feasible and indicated. For the management of pain,the following principles are established: age is not an absolute hindrance to pain assessment; a number of instruments and theobservation of pain behaviors are reliable even in patients with dementia; cyclooxygenase (COX)–2 inhibitors are preferable to COX-1inhibitors for individuals with bleeding diathesis, peptic ulcer, and Helicobacter pylori gastritis; and opioids should be slowly titratedbecause the effectiveness and toxicity become less predictable with age. In conclusion, with individualized supportive care, thesurvival and quality of life of older patients with cancer may be improved.

H. Lee Moffitt Cancer Center and Research Institute, University of SouthFlorida College of Medicine, Tampa

Address for correspondence:Lodovico Balducci, MD, University of South Florida College of Medicine, H. Lee Moffitt Cancer Center and Research Institute, 12902 Magnolia Dri, Tampa, FL 33612-9416Fax: 813-972-8359; e-mail: balducci@moffitt.usf.edu

Submitted: Aug 5, 2004; Revised: Aug 30, 2004; Accepted: Aug 30, 2005Supportive Cancer Therapy, Vol 2, No 4, 225-228, 2005

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IntroductionApproximately 60% of all cancers occur in individuals

aged ≥ 65 years, and this percentage is expected to increasewith the aging of the population.1 Older and younger indi-viduals benefit to the same extent from chemotherapy ofcommon neoplasms, but aging is associated with increasedrisk of short- and long-term complications of treatment andof cancer itself. Hence, supportive care is essential to allowthe administration of effective treatment and to preserve thefunction and the quality of life of older cancer survivors.

Age and Cytotoxic ChemotherapyAging may be construed as a progressive decline in the

functional reserve of multiple organ systems, which enhancesthe susceptibility to stress and increases the risk of function-al deterioration. For example, not only are older patients atincreased risk for neutropenic infections,1-5 but the conse-quent hospitalization is more prolonged than in youngerindividuals and is more likely to compromise the mobilityand the independence of the elderly patient.6,7 Likewise,chemotherapy-induced nausea and vomiting and cancer-

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related pain may precipitate functional dependence in olderindividuals by restricting their mobility, and may mandateprolonged and expensive rehabilitation.

Aware of this characteristic of aging, the National CancerCenter Network (NCCN) has issued a number of evidence-based guidelines aimed to ameliorate the complications andimprove the benefits of cancer treatment in the elderlypatient population (Table 1).2

Geriatric AssessmentThe aim of geriatric assessment is 3-fold:• To estimate the life expectancy and the risk of therapeu-

tic complications of older patients with cancer; these mayvary greatly among individuals in the same age group.

• To identify reversible conditions that may interfere withcancer treatment. These include depression, anemia,poorly controlled comorbid conditions, memory disor-ders, malnutrition, polypharmacy, and lack of a compe-tent home caregiver.

• To institute a common language in the classification ofolder individuals.

The classical geriatric assessment is a multidimensionalinstrument to evaluate function, comorbidity, cognition, mood,social conditions, nutrition, and pharmacy.8,9 More cost-

effective forms of assessment are explored, including home-mailed questionnaires, screening questionnaires aimed toidentify patients who benefit from a full assessment, and sim-ple tests of physical performance whose results appear corre-lated with life expectancy and risk of functionaldecline.2,10,11 Of special interest, some laboratory tests,including measurement of the concentration of interleukin-6and D-dimer in the circulation, appear predictive of mortal-ity and functional deterioration.12 Given the evolution of thefield, the NCCN does not recommend any specific instru-ment, as long as the form of geriatric evaluation selected hasbeen validated.

A decrease in glomerular filtration rate with age is almostuniversal.13 The adjustment of the doses of cyclophospha-mide and methotrexate in response to kidney function hasreduced the risk of treatment complications without com-promising the effectiveness of treatment in women aged ≥ 65years with metastatic breast cancer.14 Dose adjustmentshould include drugs whose parent compounds are eliminat-ed from the kidneys (eg, methotrexate, carboplatin, cisplatin,bleomycin, and capecitabine) as well as those that give originto active or toxic metabolites eliminated by the kidneys (eg,idarubicin, daunorubicin, and cytarabine in high doses).

Prophylactic TreatmentProphylactic treatment of patients aged ≥ 65 years with fil-

grastim or pegfilgrastim is supported by 3 lines of consideration:1. The risk of neutropenia and neutropenic infections as

well as the duration of hospitalization for neutropenic infec-tions increase at ages ≥ 65 years and is greater for patientstreated with CHOP (cyclophosphamide/doxorubicin/vin-cristine/prednisone) and CHOP-like regimens. In some stud-ies, the infection-related mortality rate was as high as 10%.2-5

Filgrastim may reduce the risk of neutropenia and neu-tropenic infections by 50%-75% according to 5 randomizedand controlled studies.15-19

2. The alternative strategy to reduce the doses of chemo-therapy has been associated with inferior results, at least incases of non-Hodgkin’s lymphomas and adjuvant chemo-therapy of breast cancer. This approach may be reasonable,however, in the case of palliative chemotherapy for metasta-tic cancer.20-23

3. Current studies of cost effectiveness show that prophy-lactic treatment with growth factors is cost effective if therisk of neutropenic infections during the first course of treat-ment is ≥ 20%.24 This is certainly the case for CHOP inpatients aged ≥ 65 years.

Additional considerations include the risk and cost offunctional dependence and the deterioration of quality of lifein older individuals undergoing hospitalization.

The European Organisation for the Research and Treatmentof Cancer (EORTC), in its guidelines for the management of

Table 1

NCCN Guidelines for the Managementof Cancer in Older Patients2

1. Patients aged ≥ 70 years should undergo some form of geriatric assessment.

2. The first dose of chemotherapy should be adjusted to the renal function of older patients; if no toxicity is seen, subsequent doses should be increased.

3. Patients aged ≥ 65 years should receive prophylactic treatment with filgrastim or pegfilgrastim when receiving chemotherapy regimens of dose intensity comparable to CHOP.

4. Hemoglobin levels should be maintained at ≥ 12 g/dL.

5. Capecitabine should be used in lieu of intravenous fluorinated pyrimidines when feasible.

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cancer in elderly patients, has issued recommendations simi-lar to those of the NCCN. While acknowledging that pro-phylactic filgrastim is indicated in individuals aged ≥ 65years who are receiving curative treatment, the EORTC rec-ommend a risk-adjusted approach.5 The American Society ofClinical Oncology (ASCO) has also studied this issue, andfinal recommendations on this topic are expected.

AnemiaAnemia is a risk factor for myelotoxicity, as the majority

of antineoplastic agents are bound to red blood cells.Anemia then causes increased concentration of free drug inthe circulation and enhanced risk of toxicity. There areother good reasons to correct anemia in older individuals.25

Anemia has been associated with fatigue and increasedprevalence of functional dependence, with increased risks ofmortality, congestive heart failure, coronary death, and thepossibly of dementia. Although treatment with epoetin ordarbepoetin is expensive, this treatment is not more expen-sive than blood transfusion and may prevent the cost ofmanagement of dependent older individuals. The EORTCand ASCO are studying the issue of managing anemia inolder patients with cancer.

Risk of MucositisThe risk of mucositis, which is mainly a complication of

intravenous fluorinated pyrimidines, increases with age.26 Inolder individuals, this complication may become rapidlylethal as a result of limited reserve. Unfortunately, no anti-dote to mucositis is available, but the substitution of capeci-tabine for 5-FU and fluorodeoxyuridine may ameliorate therisk and severity of this complication. Capecitabine is a pro-drug, activated in the liver and neoplastic tissue, with theresult of minimizing the exposure of the normal tissues to theactive compound.27 The NCCN guidelines represent a frameof reference that may accommodate new information, as theunderstanding of cancer and aging is rapidly evolving. Otheraspects of supportive care that need to be dealt with emer-gently include the prevention of nausea and vomiting, themanagement of pain, and the choice of a home caregiver.

Nausea and VomitingEven though the risk of nausea and vomiting does not

seem to increase with age, the long-term consequences of thiscomplication are of concern. These may include immobiliza-tion for fear of exacerbating the symptom and functionaldecline. The anti–neurokinin-1 agent aprepitant and thelong-lasting serotonin inhibitor palonosetron offer a newopportunity to prevent nausea and vomiting in older indi-viduals, and studies of these new compounds are needed.

Pain ManagementPain is also a major problem for older individuals with and

without cancer. Like nausea and vomiting, pain may limitthe activity of these patients and cause functional deteriora-tion.28 Basic principles related to pain management includethe following.

• Pain assessment in older individuals is generally reliable,even in those with cognitive impairment. Special strate-gies to evaluate pain include the use of vertical instead ofhorizontal pain scales, figurative pain scales, verbal paindescriptions, pain maps, and observation of pain behavior.

• COX-2 inhibitors are preferable to COX-1 inhibitors inthe presence of gastritis, recent hemorrhage, andincreased risk of bleeding.

• Older individuals are at increased risk of complicationsfrom opioids as a result of reduced excretion of mor-phine-6-glucuronide and morphine-3-glucuronide andthe possibly changed ratio of μ- and δ-opioid receptors inthe central nervous system. Treatment with opioidsshould be slowly titrated, and treatment with intrathecalmorphine infusion should be considered in patients witha life expectancy of ≥ 3 months.

• The home caregiver should be available in times ofemergency and be able to provide timely transportationto the treatment center.29 Caregiving for the olderpatient with cancer may be distressful and costly. It ben-efits the health care provider to prevent caregiver“burnout” with proper education and support.

ConclusionAge is not a contraindication to proper cancer manage-

ment; however, age is associated with increased risk of short-and long-tem complications. The NCCN guidelines for themanagement of older patients with cancer have been partlyendorsed by the EORTC and provide a framework of refer-ence for ameliorating the complications of cancer and cancertreatment and for accommodating emerging information inthis rapidly evolving field.

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