1335
Aging and Cancer
Palliative Medicine in the Elderly
James F. Cleary, M.B., B.S., F.R.A.C.P.
2 treatment-related symptoms is of importance in the practice of cancer medicine
Paul P. Carbone, M.D., D.Sc. (Hon)
1
Palliative Medicine Program, Department of
Medicine, University of Wisconsin, Madison,
Wisconsin.
2 the considerable energies that are spent in palliating symptoms in patients who
University of Wisconsin Comprehensive Can-
cer Center, University of Wisconsin, Madison,
Wisconsin.
Presented at Oncology Geriatric Education Re-
treat: Integrating Geriatrics into Oncology Train-
ing, San Juan, Puerto Rico, February 21–26,
1997.
Dr. Cleary is supported by a Faculty Develop-
ment Award of the Pharmaceutical Research
and Manufacturers of America Foundation.
Address for reprints: James F. Cleary, M.B.,
B.S., F.R.A.C.P., University of Wisconsin, Com-
prehensive Cancer Center, K6/518 CSC 600
Highland Avenue, Madison, WI 53792.
Received May 14, 1997; revision received July
18, 1997; accepted July 18, 1997.
q 1997 American Cancer Society
/ 7b71$$ge11
Cancer special section
13
Cancer is primarily a disease of the elderly and the palliation of both disease- and
in all patients. Many older patients are treated within community hospitals, in
which anticancer therapies are less likely to be given and in which the palliation
of symptoms should be of primary importance. Many oncologists struggle with
the palliation of symptoms in patients who are near the end of life. This is despite
are receiving anticancer therapies at all disease stages. The management of pain
has advanced considerably recently with improvements in pain assessment and
pharmacologic interventions. However, elderly patients are less likely than younger
patients to receive proper pain management. Elderly patients also are less likely
to take opioids for pain because of their attitudes and beliefs. Fatigue, dyspnea,
and psychologic issues also are of importance in the management of elderly cancer
patients both during anticancer therapy and near the time of death. Some elderly
cancer patients die in the care of a hospice, although many are not referred to
this service. There are many barriers to the provision of palliative medicine and
these may be related to health practitioners, to the patients themselves, or to the
health care system of which they are part. The increased educational efforts of
health professionals are needed to ensure that all patients, including the elderly,
have adequate palliation of their cancer-related symptoms. Cancer 1997;80:1335–
47. q 1997 American Cancer Society.
KEYWORDS: palliative medicine, symptom management, pain, fatigue, dyspnea,
hospice, death, cancer.
C ancer is primarily a disease of older people. Greater than 50% of
cancers and 60% of cancer-associated deaths in the U.S. occur in
people age ú 65 years. As the world population ages, issues of cancer
care, especially palliation, will become increasingly important in the
field of medical oncology. Moreover, studies by Newcomb and Car-
bone1 and Begg and Carbone2 have shown that older people are more
likely to be diagnosed and treated in smaller hospitals and therefore
are less likely to be referred to cancer centers. These patients are
not recruited to clinical trials and are less likely to receive standard
chemotherapy for the treatment of their disease. This may imply ei-
ther that elderly patients are not receiving adequate anticancer treat-
ment or that an increasing emphasis is being placed on their symp-
tomatic care. In the elderly and particularly those who are frail, pallia-
tion may be the primary objective of cancer treatment.
The priorities of the medical profession as stated in the Hippo-
cratic Oath have been to prolong life and to prevent suffering. How-
ever in recent decades far greater priority has been placed on the
prolongation of life with little focus placed on the prevention of suffer-
ing. Death has been viewed as another disease that can be cured
rather than as a normal part of living. Modern palliative care was
09-08-97 14:43:49 cana W: Cancer
1336 CANCER October 1, 1997 / Volume 80 / Number 7
born within St. Christopher’s Hospice in London un-
der the guiding hand of Dame Cecily Saunders during
the 1960s and since then has grown extensively
throughout the world. The importance of care of the
dying has been highlighted by the inclusion of pallia-
tive care within medical school curriculums in some
countries3 and the recognition of palliative medicine
as a specialty within countries such as the United
Kingdom, Canada, and Australia. The Royal College of
Physicians4 states that palliative medicine is ‘‘the study
and management of patients with active, far advanced
disease for whom the prognosis is limited and the fo-
cus of care is quality of life.’’
The World Health Organization (WHO)5 has de-
fined palliative care as being the ‘‘active & total care of
a person whose condition is not responsive to curative
therapy.’’ Such care is applicable both near the end
of life and early within a disease process in conjunc-
tion with other anticancer treatments. Palliative care,
as outlined by WHO, should neither intend to nor
postpone death but should affirm life and regard dying
as a normal process. The intention of palliative care
is to provide relief from pain and other symptoms and
to integrate psychologic and spiritual aspects of care.
Palliative care offers support systems to help patients
live as actively as possible until death and it helps
families cope with the patient’s illness as well as death.
The term ‘‘palliation’’ is not one that is well recognized
by clinicians in the U.S. However, ‘‘hospice’’ is a well
known concept in the U.S., but is viewed by many to
involve the care of those who are ‘‘actively dying.’’
There has been some separation of the modern hos-
pice movement from mainstream medicine since its
formation in the U.S. in the early 1970s. This gap cur-
rently is closing as end of life care gains prominence
within the health care system and the community. It
is important to address the role of palliative medicine
within cancer medicine.
Palliative Medicine: Not Just for The Dying
The goals of treatment for all cancer patients, irrespec-
tive of age, need to be defined clearly for the benefit
of both clinicians and cancer patients. Miller6 defined
four categories of intention, namely curative, active
palliation, palliative/symptom control, and support-
ive. The term ‘‘active palliation’’ is probably better
termed ‘‘prolongation of survival’’ (Table 1). Levy7 ad-
dressed the continuum of care ranging from ‘‘curative
through to terminal care.’’ Cure often is a difficult term
to define and has for many years been equated with
5-year disease free survival, based on the leukemia
experience. Five- or 10-year survival figures may not
be important endpoints for elderly patients. Eckhardt
has defined cure to be the treatment of cancer in such
/ 7b71$$ge11 09-08-97 14:43:49 cana
a way that it does not interfere with the normal length
of the individual’s life or with the quality of the per-
son’s life by producing symptoms.8 The importance of
quality of life in the definition of cure highlights the
importance of symptom management for all cancer
patients. In addition to symptoms of cancer, elderly
patients often have symptoms associated with other
illnesses that need to be integrated into the overall
plan of care. Elderly patients often will be at much
greater risk of dying of these associated diseases than
of their cancer.
MacDonald proposed the assimilation of palliative
medicine within the practice of oncology,9 and spoke
of the importance of palliative medicine in cancer cen-
ters both to strengthen the provision of cancer services
within these centers and to improve the research base
of palliative medicine.9 MacDonald proposed symp-
tom control or control of suffering as being the fourth
arm of cancer control with the other three arms being
1) primary prevention, 2) early detection, and 3) treat-
ment of established cancers,9 a proposal adopted by
the National Cancer Institute. However, to date little
emphasis and resources have been placed into the
fourth arm, with most resources being allocated to the
first three arms. This is brought out by the WHO, which
described the lack of support of palliative medicine
diagrammatically (Fig. 1). WHO has suggested that
there should be an integrated approach within oncol-
ogy and palliation, with a gradual increase in resources
to palliation throughout a patient’s illness,5 consistent
with the continuum of care suggested by Levy.7 This
integration can be interpreted to mean that early
within a patient’s illness, there is some focus on symp-
tom control but that as disease progresses, the focus
tends to become increasingly directed to symptom
control. However, this model of integration of symp-
tom control should not be limited to only those indi-
viduals who are dying or have incurable cancer. Much
of what a cancer specialist does in his or her daily
practice is, in fact, symptom control. In the elderly
who are frail, symptom control may be the primary
objective of therapy.
To illustrate this further, consider the case of a
elderly patient with colorectal carcinoma. In a patient
with a Dukes Stage A tumor that is surgically removed,
the early focus is on treating symptoms related to sur-
gery and the consequences of surgery, which may in-
clude the management of a colostomy, often a difficult
concept for an elderly person. If the patient has a
Dukes Stage B2 or C tumor, the decision would be
to give the patient adjuvant 5-fluorouracil (5-FU) and
levamisole. Again, most of the physician’s energies are
concentrated on treating the therapy-related side ef-
fects such as mucositis, nausea, and infection to en-
W: Cancer
 Palliative Medicine in the Elderly/Cleary and Carbone 1337

TABLE 1
Definition of Various Stages of Cancer Treatment

Prolongation of Palliative/
Curative survival symptom control Supportive

Goal Cure Quality of survival Quality of life Comfort

Disease impact Eradicate Arrest growth Response None
Psychologic Win Fight Accommodate None
Physician role Encourage Encourage Support Support
Side effects Major Major/moderate Minor None
Life support Yes Probably Probably not None
Hospice No Probably not Probably Yes

Adapted from Miller RJ. Supporting a cancer patient’s decision to limit therapy. Semin Oncol 1994;21:787–91.

ment-related symptoms. In elderly persons who may

FIGURE 1. (A) The current relationship between palliative care and can-
cer therapy and (B) that proposed by the World Health Organization show-
ing integration between palliative care and medical oncology in the care
of dying patients.
sure both the patient’s comfort and completion of
treatment. A patient who presents with or in whom
disseminated cancer develops, may be treated with
combination chemotherapy using 5-FU and leuco-
vorin, or entered into Phase 1 clinical trials of new
agents. Patients who are age ú 70 years may need to
have the dosages of 5-FU and leucovorin modified to
diminish the gastrointestinal toxicity associated with
this treatment. Again, the physician’s energies are di-
rected toward managing both the disease and treat-
have difficulty coming into the clinic, this option may
be less viable and arrangements may need to be made
to provide the best supportive care. After a lack of
therapeutic response, the physician should concen-
trate even more energy into providing good palliative
care.
The assimilation of palliative medicine within all
aspects of cancer medicine is depicted in a modifica-
tion of the WHO model of the provision of palliative
care (Fig. 2). However, many physicians appear to find
it difficult to provide symptom management to pa-
tients unless they are administering chemotherapy.
Many of the symptoms occurring near the end of life
are similar in nature to those observed with chemo-
therapy and radiotherapy regardless of the intention
of the treatment. Oncologists devote most of their en-
ergies to providing symptom control and should con-
tinue to do so in elderly patients in whom antitumor
therapy is no longer a useful option and in those pa-
tients in whom death is imminent. This should defi-
nitely include therapy for those in whom best support-
ive care without the use of antitumor therapy is the
best option.
Palliation of Symptoms
There is great variability in the range of symptoms
experienced by cancer patients. The proposed revision
of the National Cancer Institute’s Clinical Toxicity Cri-
teria has more than 200 individual items with which
to measure the toxicity of cancer drugs. Many symp-
toms are observed in patients near death. Seale and
Cartwright10 studied both the incidence of symptoms
in patients near death and the effect of age on these
symptoms (Tables 2 and 3). Two populations were
studied in the United Kingdom in the years 1969 and
1987, with 785 and 639 patients for each year, respec-
tively. Approximately 80% of cancer patients in both

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1338 CANCER October 1, 1997 / Volume 80 / Number 7
FIGURE 2. The relation between medical oncology and palliative medi-
cine at all stages of cancer therapy, showing the importance of symptom
management for all patients. (A) Cured patient or patient with ongoing
symptoms related to treatment. (B) Patient in whom survival is prolonged
but in whom disease and associated symptoms are always present. (C)
Patient in whom palliation is the goal; treatment may include chemotherapy
and other therapies with antitumor activity.
years experienced pain whereas approximately 67% of
noncancer patients experienced pain. Of interest,
there was no difference in the incidence of pain with
age. The incidence of mental confusion, loss of bladder
control, difficulty seeing and hearing, and dizziness
was observed to increase with age, whereas the inci-
dence of a persistent cough decreased with age (Table
3). At this point in the article, the assessment and
management of a number of symptoms of particular
importance in cancer, including cancer pain, will be
reviewed.
Pain
Pain can occur at any stage within a patient’s course
of cancer and its management has been given too little
attention by health professionals. Although most can-
cer pain can be controlled adequately with oral analge-
sics, a significant percentage of cancer patients receive
analgesics that are inadequate in type or potency to
manage their pain. In a recent multicenter study of
outpatients with metastatic cancer treated at Eastern
Cooperative Oncology Group (ECOG) Centers, at least
/ 7b71$$ge11 09-08-97 14:43:49 cana
42% of those with pain did not receive the type of
analgesics recommended by standard cancer pain
management guidelines.11 In that study, patients age
ú 70 years were among specific populations at greater
risk for inadequate analgesia. The persons at greatest
risk for inadequate analgesia were elderly, female pa-
tients from a minority racial group. Poorly controlled
pain may have such a catastrophic effect on the pa-
tient and his or her family that proper pain manage-
ment must have the highest priority for those who
routinely care for cancer patients. Special care must
be exercised to ensure that older patients obtain pain
relief. Severe pain may be a primary reason why pa-
tients, with the support of their families, stop cancer
treatment, and often is given as a reason why patients
and families entertain the idea of euthanasia or physi-
cian-assisted suicide. Improvement in the anticipa-
tion, evaluation, and treatment of pain will benefit
all cancer patients. Recognizing the specific barriers
confronting the management of pain in all patients,
including the older patient, will help ensure adequate
pain relief.
Prevalence, severity and risk of pain
Although only 15% of patients with nonmetastatic dis-
ease had pain associated with their tumor at the time
of diagnosis,12 pain becomes more pervasive as the
disease progresses. With the diagnosis of metastatic
disease, the incidence of cancer pain has increased to
74% and up to 87% of patients will have pain prior to
death.10 In a multicentered study, 67% of outpatients
with metastatic disease had disease-related pain or
were taking analgesic medication on a daily basis.11
Thirty-six percent of the patients in this ECOG study
had pain severe enough to compromise their daily
function.
Etiology of cancer pain
The sensation of pain is generated either by stimula-
tion of peripheral pain receptors or by damage to affer-
ent nerve fibers. This is the basis of the classification
of pain. Pain due to stimulation of pain receptors, ei-
ther by pressure, compression, traction, or disease-
related chemical changes, is called nociceptive pain.
Damage to visceral, somatic, or autonomic nerve
trunks produces spontaneous activity in nerves and is
termed neuropathic pain. Cancer patients often have
both nociceptive and neuropathic pain simultane-
ously. In patients with advanced cancer, the majority
of patients have pain at multiple sites caused by multi-
ple mechanisms (Table 4).13
Direct tumor involvement is the most common
cause of pain, present in approximately 67% of pa-
tients with pain from metastatic cancer. Tumor inva-
W: Cancer
 Palliative Medicine in the Elderly/Cleary and Carbone 1339

TABLE 2
Percentage of Symptoms Present in Cancer and Noncancer Patients Prior to Death in 1969 and 1987

Cancer deaths Other deaths All deaths

1969 1987 1969 1987 1969 1987

% % % % % %

Pain 87 84 58 67 66 72
Trouble with breathing 47 47 44 49 45 49
Loss of appetite 76 71 37 38 48 47
Drowsiness 44
Sleeplessness 69 51 41 36 49 40
Mental confusion 36 33 36 38 36 37a
Depression 45 38 31 36 36 36
Constipation 42 47 23 32 28 36
Loss of bladder control 38 37 29 33 32 34a
Dry mouth/thirst 33
Vomiting 54 51 21 27 30 33
Backache 31
Difficulty swallowing 23
Loss of bowel control 37 25 24 22 28 23a
Bad temper 23
Bed sores 24 28 13 14 16 18
Unpleasant smell 26 19 11 13 15 14
Dribbling 13
No. of deaths (n Å 100%) 215 168 570 471 785 639

a
Symptoms with age-related difference.
Adapted from Seale C, Cartwright A. The year before death. Brookfield, VT: Ashgate Publishing Company, 1994.

TABLE 3
Variation with Age of Symptoms Near the Time of Death from all Causes

Age (yrs)

õ55 55–64 65–74 75–84 ¢85

Mental confusion 21 25 26 43 52
Loss of bladder control 24 16 24 38 51
Loss of bowel control 19 8 19 25 32
Difficulty seeing 10 5 19 24 46
Difficulty hearing 4 7 20 31 54
Dizziness 22 18 25 38 33
Persistent cough 28 30 30 17 10
No. of deaths (n Å 100%) 62 80 147 203 147

Adapted from Seale C, Cartwright A. The year before death. Brookfield, VT: Ashgate Publishing Company, 1994.

sion of bone, common in patients with breast and counts for up to 20% of those patients who report pain
prostate carcinoma and those with multiple myeloma, with metastatic cancer. The effect of aging on the side
accounts for pain in approximately 50% of these pa- effects of chemotherapy has been documented. Begg
tients. The remaining 50% experience tumor-related and Carbone2 assessed the toxicities of 25,000 patients
pain that is due to nerve compression or infiltration, treated on Eastern Cooperative Oncology Group stud-
or involvement of the gastrointestinal tract or soft tis- ies and concluded that the elderly generally tolerate
sue. Up to 25% of patients may have pain related to chemotherapy as well as younger patients with a simi-
their therapy.12 Persistent posttherapy pain, resulting lar performance status. However, they suggested that
from surgery, radiotherapy, or chemotherapy, ac- in general the elderly appear more susceptible to the

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1340 CANCER October 1, 1997 / Volume 80 / Number 7

TABLE 4 languages and has allowed the definition of pain into

Etiology of Cancer-Associated Symptoms categories of mild (0 – 4), moderate (5 – 6), and severe
(7 – 10).18 Pain assessment in the elderly also may be
Caused by cancer Bone, visceral, soft tissue, and brain
involvement; spinal cord compression; nerve complicated by disease processes that effect a pa-
infiltration; ulceration { infection; tient’s ability to communicate. In this situation, clini-
Related to cancer constipation; bed sores; zoster virus; cians may have to rely on nonverbal communication
candidiasis lymphedema. and signs to adequately assess pain.
Related to cancer therapy
Surgery Thoracotomy, mastectomy, laparotomy, radical
cervical lymph node dissection The pharmacologic management of pain
Chemotherapy Neuropathy, mucositis, phlebitis The recent Agency for Health Care Policy and Research
Radiation Brachial plexus fibrosis, myelopathy, mucositis, (AHCPR) guidelines19 for the management of cancer
esophagitis pain recommend that patients initially be treated ac-
cording to the severity of their pain. Mild pain can be
Adapted from Ripamonti C, Bruera E. Pain and symptom management in palliative care. Cancer Causes
Control 1996;3:204–13. treated with analgesics such as nonsteroidal antiin-
flammatory drugs (NSAIDs) or acetaminophen. For
moderate pain, opioids such as codeine, low doses
of oxycodone, or morphine are given. Severe pain is
neuropathy associated with cisplatin and the vinca al- treated with full doses of opioids including morphine,
kaloids and recommended that these agents should oxycodone, hydromorphone, or fentanyl. Consider-
be used sparingly in the elderly population because of ation of the use of adjuvant medications is recom-
the risk of neuropathy. mended in all patients and should include the use
A new report of pain in a patient with metastatic of NSAIDs together with opioids in the case of bony
cancer first should be thought of as disease-related, metastases. Adjuvant medications may result in a de-
but noncancer causes may need to be considered and crease in opioid dose with an associated decrease in
ruled out. The prevalence of comorbidities that cause side effects, although this is still a subject of further
pain, such as osteoarthritis, is much greater for an study. Adjuvant therapy should be used with caution
older population. Elderly persons experience more in the elderly and patients should be monitored care-
pain in general than the young. The prevalence of pain fully for the occurence of side effects and drug interac-
in those older than 60 years is 250/1000, double that tions.
of those age õ 60 years.14 The predominant cause of Physicians have an extensive array of analgesic
pain in the elderly is musculoskeletal, with 80% people agents available to use in the management of cancer
age ú 65 years suffering from arthritis. Approximately pain. The dose of pain medications are titrated upward
25 – 50% of community dwelling elderly suffer im- until either a patient’s desired pain relief or until un-
portant pain problems15 whereas up to 80% of patients manageable side effects are reached. In the case of
living in nursing homes have pain.16 The older patient NSAIDs and acetaminophen, dose escalation will be
with cancer not only is likely to experience pain in limited by either side effects or the expectation of side
association with his/her cancer, but is more likely than effects. The dose-limiting component of formulations
a younger person to have pain associated with other such as codeine/acetaminophen or oxycodone/acet-
disease processes. It has been suggested that apart aminophen formulations is the total daily dose of acet-
from pain associated with joints (arthritis), elderly pa- aminophen or aspirin. Opioids in their own right do
tients experience less pain than younger patients and not have a fixed ceiling dose, the highest dose being
differences in the perception of pain in the elderly that which provides analgesia with manageable side
have been recorded by some investigators. Despite effects. Dose escalation of opioids in the elderly should
these findings, biologic aging appears to have no im- proceed cautiously because there is some evidence
pact on the sensory or perceived unpleasantness of that the metabolism of morphine is decreased in the
pain17 and treatment of pain in the elderly should fol- elderly and either smaller doses of opioids or increased
low the same principles as in younger patients. dosing intervals are needed to allow the same analge-
The presence of these multiple pains may make sic effect as in younger patients.20 – 22
pain assessment in the elderly a challenge. The most Analgesic agents should be taken on a regular
commonly used tool in the measurement of pain is around the clock basis, not on an ‘‘as needed’’ basis.
the numeric rating index, in which patients are asked This relates to the need to maintain adequate levels
to rate their pain numerically on a scale of 0 to 10 in of an opioid in the body and is more likely to maintain
which 0 is no pain and 10 is the worst pain that they a patient in a pain free state.23 Rescue or ‘‘as needed’’
could possibly imagine. This has been used in multiple medications should be ordered for all patients and

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should be used for episodes of breakthrough pain and
during periods of titration (either upward or down-
ward titration) of analgesic agents. Current recom-
mendations for rescue doses range from 5 – 15% of the
daily dose24 (or 10 – 30% of the 12-hour dose).
The initial treatment and titration with opioids
should take place with immediate release preparations
of opioids.25 The prolonged absorption of a sustained
release product may result in prolonged side effects
in a patient who is receiving opioids for the first time.
However a patient who is taking Percocett (DuPont
Pharmaceuticals, Manati, Puerto Rico) is not opioid
naive and can be changed to a sustained release prod-
uct. Twelve Percocett tablets are the equivalent of 60
mg a day of oral morphine. Oxycodone, the active in-
gredient in Percocett, is a drug that has an analgesic
activity similar to morphine and that now is available
as a sustained release product. The use of sustained
release products has made twice daily dosing of anal-
gesics a reality for cancer patients and once daily mor-
phine products are currently avalable. However, there
is no measured difference in the side effects and anal-
gesia between immediate release morphine adminis-
tered every 4 hours and sustained release morphine
administered twice a day.26 Patients who achieve anal-
gesia with twice daily dosing, but in whom analgesia
is not sustained for the full 12 hours, may benefit from
8-hour dosing. Patients who do not achieve adequate
analgesia at all should have their sustained release
dose increased. Methadone, another oral opioid more
commonly associated with drug withdrawal programs,
is a cheap and effective alternative for the treatment
of cancer pain. Methadone has a long half-life and
therefore dose escalation must proceed cautiously, es-
pecially in the elderly to reduce the occurrence and
severity of side effects.
Ideally, pain medications should be given orally.
However, some patients cannot tolerate the oral route.
In the study by Zech et al.,27 approximately 80% of
the 2118 patients were managed with oral medications
throughout their illness. This decreased to 50% of the
864 patients being cared for in the hospital at the time
of death. Therefore, alternative methods of drug deliv-
ery need to be considered in those patients in whom
oral administration is not possible. Many people use
the sublingual route, believing that this provides rapid
analgesia. There is increasing evidence that the sublin-
gual administration of morphine provides no benefit
over oral administration. Peak plasma concentrations
of morphine occur later and at lower levels after sub-
lingual administration than for oral administration.28
It also may be preferable to use morphine solutions
rather than sublingual tablets, which have a bitter
taste. The rectal administration of opioids is not lim-
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Palliative Medicine in the Elderly/Cleary and Carbone 1341
ited to drugs for which there is a suppository formula-
tion; sustained release tablets administered rectally
provide effective analgesia.
The transdermal delivery of opioids currently is
limited to fentanyl. The rate of delivery of fentanyl (mg/
hour) is dependent on the surface area of the patch
applied, with rates ranging from 25 – 100 mg/hour.
When administered transdermally, the drug accumu-
lates in the subcutaneous fat, and then diffuses pas-
sively into the blood stream to result in sustained
plasma concentrations. Current recommendations are
that patients should be stabilized on oral opioids prior
to the administration of transdermal fentanyl and that
dose changes should not be made more frequently
than every 72 hours.29 As always, patients need to be
given a short-acting opioid, such as immediate release
morphine, for breakthrough pain; oral transmucosal
fentanyl citrate, currently approved for preoperative
sedation in children, may be a useful rescue medica-
tion for cancer patients.30
The parenteral administration of opioids may be
necessary in those who cannot swallow, who have in-
tractable side effects, or in whom rectal delivery is not
desirable. Subcutaneous infusions have been exten-
sively used in Canada31 and Australia, but are not com-
monly used in the U.S., possibly because many cancer
patients have intravenous ports. The steady plasma
concentrations of opioids, resulting from either intra-
venous or subcutaneous infusions, may result in a
diminution of side effects and therefore an optimiza-
tion of analgesia. Only a small percentage of cancer
patients (2 – 5%) will require interventions or the direct
delivery of opioids to the central nervous system.27
Patients with unmanageable side effects may benefit
from epidural or intrathecal administration of opioids.
Approximately 10% of the intravenous dose of an opi-
oid needs to be administered epidurally and 0.1% of
the dose administered intrathecally. These procedures
are costly and require catheters and pumps to deliver
drug. A patient must be expected to use such devices
for ú3 months and without complications to show
cost-effectiveness.
The intramuscular injection of opioids is to be
avoided. Apart from being painful for the patient, ab-
sorption after injection is erratic and in most cases
results in an analgesic effect that parallels the oral
administration of an equivalent dose of the same drug.
One opioid commonly given by intramuscular injec-
tion is meperidine or pethidine. Meperidine is in fact
a drug that has very few indications in the treatment
of pain. Meperidine has short-acting analgesic activity
(one-tenth that of morphine) and mostly is prescribed
at subtherapeutic doses (50 – 75 mg intramuscularly
every 3 – 4 hours). It is metabolized to normeperidine,
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1342 CANCER October 1, 1997 / Volume 80 / Number 7
a toxic metabolite that accumulates with repeated ad-
ministration and results in confusion, hallucinations,
and seizures. If used at all, meperidine should be used
for no more than 48 hours and with a dose limitation
of 600 mg/day. This dose limitation should be 450 mg/
day in patients with of renal impairment, which occurs
more commonly in the elderly. Given these limita-
tions, meperidine is not recommended for the routine
treatment of pain, particularly in the elderly.
Fatigue
Fatigue is reported by up to 90% of cancer patients. It
is experienced by many patients receiving both che-
motherapy and radiotherapy and may persist for many
months after patients have completed therapy. It also
is a prevalent symptom in patients near the end of
life and may occur together with the cancer cachexia
syndrome. Fatigue in the elderly also is a common
symptom often not associated with cancer or its treat-
ment. One needs to look for treatable causes, namely
anemia, diarrhea, renal failure, hypothyroidism, and
hypercalcemia. Depressed patients also may present
with fatigue and clinical depression needs to be care-
fully considered in all elderly patients who present
with fatigue. Despite the widespread occurrence of
this symptom in patients with all stages of cancer,
there has been relatively little activity directed toward
the management of fatigue, caused, in part, the au-
thors believe, by the difficulty in defining fatigue. Fa-
tigue is a multidimensional symptom that can be de-
scribed in terms of the physical, mental, and psy-
chologic components of a person’s life. To address
the multiple aspects of fatigue, the Multidimensional
Fatigue Index has been developed in Holland.32 This
tool has been validated in different cancer and non-
cancer populations and in several languages. A fatigue
subscale of the functional assessment of cancer ther-
apy (FACT) quality of life index also has been devel-
oped.33 Based on the efforts of the Pain Research
Group at the University of Wisconsin, the Brief Fatigue
Inventory currently is in development. The numeric
rating of fatigue by self-report will allow correlation
with a number of biologic markers that are also being
measured in these patients. Using the effect of fatigue
on patient’s daily activities, fatigue may be classified
in the same way as pain (mild, moderate, or severe).18
There are little data supporting therapeutic interven-
tions in the management of fatigue at this stage.
Dyspnea
Dyspnea refers to the sensation of ‘bad breathing’
(dyspnoia), a symptom experienced by up to 75% of
lung carcinoma patients and by approximately 70% of
patients close to death in a hospice setting.34 In 24%
/ 7b71$$ge11 09-08-97 14:43:49 cana
of these hospice patients, no underlying cardiac cause
was identified as a cause of the dyspnea. Approxi-
mately 41% of palliative care patients have been docu-
mented to have dyspnea and 46% describe it as being
of moderate to severe intensity.35
Dyspnea is often associated with hypoxia but may
occur without hypoxia, particularly in the presence of
some of the disease manifestations of cancer, includ-
ing superior vena cava syndrome, pleural disease, and
bronchial obstruction. Reversible causes of dyspnea
should be sought and managed appropriately. Many
patients may have bronchoconstriction that will re-
spond to beta-receptor agonists, methylxanthines, and
corticosteroids. Steroids may be useful in the manage-
ment of obstruction and lymphangitic spread. The re-
lief of obstruction, and consequently of dyspnea, with
laser therapy and/or stents may provide very good
symptomatic relief to some patients. Continuous oxy-
gen therapy is most commonly associated with
chronic obstructive airway disease (COAD), for which
it is used to reduce pulmonary hypertension. In cancer
patients, oxygen primarily is used to reduce dyspnea.
Maximum relief has been found in cancer patients
who are hypoxic with dyspnea at rest.36 However, in-
termittent oxygen can be beneficial for exertional dys-
pnea. The delivery of oxygen though a concentrator
(nitrogen extractor) is preferable to cylinders and the
use of nasal cannulae rather than a mask may allow
patients to function at a higher level. The flow rate of
the oxygen should be directed at patient comfort. The
measurement of oxygen saturation may assist in titrat-
ing flow rates whereas in those patients who retain
carbon dioxide, arterial blood gas analysis may be nec-
essary.
Opioids have been used with great effectiveness
in the treatment of acute dyspnea. Morphine is part
of the primary treatment in patients with cardiac fail-
ure in whom it vasodilates, depresses respiratory rate,
and alters the sensation of dyspnea. Sublingual, oral,
and intravenous morphine commonly are used in the
treatment of cancer-associated dyspnea with good ef-
fect.37 For continuous dyspnea, small doses of long-
acting morphine may be effective. Pain often is an
associated symptom and the use of opioids will be
directed primarily at that symptom, providing relief of
dyspnea at the same time. Intermittent (breakthrough)
dyspnea can respond to ‘‘as needed’’ opioids. There
have been few studies to elucidate opioid use in these
situations. It always is important to ensure whether
another therapy (drug or nondrug) may be more suc-
cessful. One must bear in mind the standard principles
of drug therapy in the elderly to ensure that the addi-
tion of these therapies does not contribute to side ef-
fects that may affect the patient’s quality of life. The
W: Cancer

side effects may be related to decreased clearance of
drugs or the increased risk of drug interactions due to
polypharmacy.
Delivering drugs to the target receptors may be
of great advantage, particularly in the elderly. Opioid
receptors have been identified in the airways and it
has been suggested that nebulized opioids may be use-
ful for the treatment of dyspnea. Advantages of the
nebulized delivery include direct action in the airways
and the availability of a large surface area to provide
rapid and efficient delivery of the drug. Many patients
with lung carcinoma are familiar with the use of nebu-
lizers in the treatment of underlying lung disease. Mor-
phine delivered by nebulizer has shown one-sixth the
difference in peak plasma levels38 and the delivery of
5 mg by nebulizer is the equivalent of 1.7 mg morphine
administered intravenously. Five milligrams of nebu-
lized morphine resulted in a 35% increase in exercise
capacity in COAD patients.39 Despite a lack of studies
in cancer patients to clarify the efficacy of nebulized
morphine, its use is increasing within hospice circles.
Care needs to be taken when administering morphine
by nebulizer. Bronchospasm may result and therefore
a test dose should be given in the clinic setting. There
is some suggestion that fentanyl may be a better op-
tion because it is associated with less histamine re-
lease. Other side effects of nebulized morphine are
commensurate with equivalent parenteral doses.
Respiratory sedatives also are widely used in the
treatment of dyspnea. Few studies have been per-
formed in cancer patients that address the use of com-
pounds such as phenothiazines and benzodiazepines.
Promethazine has been shown to reduce dyspnea in
COAD patients. Diazepam, 5 mg, administered to
COAD patients resulted in improved sleep and had
no effect on nocturnal hypoxia. There are concerns
regarding carbon dioxide retention in COAD patients.
Lorazepam is a relatively quick-acting benzodiazepine
that can be administered orally, sublingually, or intra-
venously. Midazolam can be administered as an infu-
sion either intravenously or subcutaneously. However,
further research on the use of these drugs needs to
take place.
Psychologic and Psychiatric Symptoms
Psychologic and psychiatric symptoms commonly oc-
cur in patients with advanced cancer and include anxi-
ety, depressive, cognitive, and existential disorders.40
All these symptoms may have an organic cause that
may require exclusion and treatment. Anxiety disor-
ders may include excessive worry, restlessness, poor
concentration, irritability, tension, and sleep distur-
bances. These symptoms also may be due to hypoxia,
septicemia, uncontrolled pain, or drug reactions. De-
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Palliative Medicine in the Elderly/Cleary and Carbone 1343
pressive disorders also may present in patients with
fatigue, poor concentration, sleep disorders, and sui-
cidal thoughts. It may be appropriate to search for the
etiology of such symptoms, which may include pain,
medications, endocrine abnormalities as a result of
treatment, or the side effects of the anticancer thera-
pies themselves. Cognitive disorders may occur in the
form of disturbances of consciousness or language,
delirium, disorientation, memory impairment, and
changes in perception. Patients may have unfilled as-
pirations or goals within their lives or unresolved guilt
potentially linked to difficulties within relationships.
Finally, the anticipation of suffering and the fear of
death may be a major concern in all patients, not just
those with cancer, and for their relatives. In elderly
patients, assessment of underlying mental or cognitive
disorders can be aggravated or confused with prob-
lems or side effects with medications.
The Management of Symptoms in Patients Near Death
There were an estimated 2,225,000 million deaths in
the U.S. in 1994, 65% of which were from three dis-
eases: cardiovascular (33%), cancer (25%), and neuro-
vascular (7%) causes.41 Most deaths occur in patients
age ú 65 years and 67% of cancer deaths occur in
those age ú 65 years. Within the U.S., 62% of all deaths
occur in hospitals, 16% in nursing homes, and 17% at
home. It is estimated that only 10% of deaths in the
U.S. occur under the care of hospice, a philosophy and
funding mechanism oriented toward the care of the
dying. Some 80% of hospice patients are Medicare
beneficiaries and therefore are considered by some to
be elderly.
In a review of the 1990 Medicare claims data,
Christakis and Escare ascertained the use of hospice
care in the elderly.42 The mean age of patients from 5
states (Texas, Florida, California, Illinois, and New
York) was 76.4 years and 80% were cancer patients.
The predominant malignancies were lung carcinoma
(21.4%), colorectal carcinoma (10.5%), and prostate
carcinoma (7.4%). The predominance of these malig-
nancies is consistent with the overall sites of cancer
deaths.43 However, breast carcinoma is not highly rep-
resented in the Medicare hospice population. This
may be due to the earlier age of diagnosis of breast
carcinoma and the less aggressive nature of post-
menopausal breast carcinoma. The median survival of
the patients admitted to hospice was 36 days and
15.6% of the 5700 patients died within 7 days of admis-
sion. These figures are very similar to the data ob-
tained in the National Hospice Study of the late 1970s
and early 1980s. In that study, the median length of
survival was 35 days and 20% of patients died within
7 days of admission.44 It is currently estimated that
W: Cancer
1344 CANCER October 1, 1997 / Volume 80 / Number 7
33% of cancer deaths in the U.S. will occur in patients
under the care of a hospice. In other settings, 50% of
cancer patients who die have contact with hospice
services.45 In the authors’ county (Dane County, Wis-
consin), at least 62% of cancer deaths occur in the care
of a hospice, although many of these patients continue
to have short lengths of stay (50% for õ1 month). Ap-
proximately 80% of hospice patients in Dane County
are covered under the Medicare Hospice Benefit.
Barriers to the Provision of Palliative Medicine
It is interesting to review some of the barriers to the
provision of palliative care throughout the health care
system. This has been best explored in the area of pain
management. There are many barriers to good cancer
pain management and they have been detailed by the
AHCPR Cancer Pain guidelines.19 These barriers may
be related to health practitioners, to patients them-
selves, or to the health care system of which they are
part.
Oncologists have acknowledged that they are not
properly trained in pain assessment46 and often will
not address the issue of pain unless it is volunteered by
the patient. To provide adequate pain control, health
professionals need to use a patient’s report of pain as
the primary means of assessment. Many cancer pa-
tients fear that reporting pain will distract their clini-
cians from their disease and its treatment with cyto-
toxic therapy and therefore do not report it.47 This may
be of more importance in the elderly, who often have
multiple disease processes present. Poor or absent
pain assessment has been identified as one of the ma-
jor reasons for poor cancer pain management.
Reimbursement issues are of significance in the
management of cancer pain. A proper pain assess-
ment, particularly for a patient with multiple causes
of pain, takes time and may be limited by the time a
doctor can afford to spend with each patient. Proper
pain assessment and management is poorly rewarded
because it consumes an extended period of the physi-
cian’s time. Cost also becomes a factor in relation to
the availability of medications. Most cancer patients
should be able to have their pain managed on an out-
patient basis. However, many elderly patients in the
U.S. are covered by Medicare, which does not reim-
burse the cost of outpatient oral analgesics even
though it pays for the cost of inpatient medications.
Patients themselves may not fill prescriptions for opi-
oids, despite the pain they may be experiencing, be-
cause of the extra cost of these drugs to them. Pro-
posed changes to health care in the U.S. may impact
severely on funding to Medicare and consequently on
cancer pain management in the elderly. Other health
care organizations (e.g., health maintenance organiza-
/ 7b71$$ge11 09-08-97 14:43:49 cana
tions, insurance companies) already vary greatly in
what they provide for pain management but may be-
come a driving force in ‘‘standard pain management,’’
not necessarily through optimizing patient care but in
optimizing profits.
What patients think regarding pain and its treat-
ment can be very important in the provision of ade-
quate pain management. Ward et al.47 assessed pain
severity and pain interference together with concerns
regarding the reporting of pain and use of pain medi-
cation in 270 cancer patients. The eight specific issues
addressed included fear of addiction, beliefs that
‘‘good’’ patients do not complain about pain, and con-
cerns regarding side effects. Some patients believed
that physicians were not interested in their pain (37%
of patients), many were concerned about addiction
(55%), and most were anxious about constipation as
a side effect of cancer pain management (85%). There
were more concerns in those patients with less educa-
tion, lower incomes, higher levels of pain, and those
who were undermedicated. It is important to note that
older patients had more concerns in all areas.
Fear of addiction is a special concern for older
patients and also may be a concern for their families
and their health care providers. There is little rational
evidence to support this concern. Of 12,000 patients
prescribed opioids for medical purposes, õ0.1% be-
came addicted to these medications.48 Confusion in
the terminology associated with addiction and physi-
cal dependence contributes to this problem. Physical
dependence is a physiologic phenomenon character-
ized by the development of an abstinence syndrome
after the abrupt discontinuation of therapy, substan-
tial dose reduction, or the administration of an antago-
nist drug.49 Physical dependence will develop in pa-
tients who are prescribed opioids for any length of
time in a situation similar to that of any patient who
has been prescribed corticosteroids over time. When
an opioid is stopped suddenly, the patient experiences
physiologic withdrawal symptoms that may include
fever, tachycardia, and abdominal cramps. The occur-
rence of withdrawal symptoms has been used by many
to establish the diagnosis of substance dependence.
A more usable definition of addiction or psychologic
dependence allows the diagnosis to be made based on
the presence of three types of aberrant behavior. These
are 1) a patient’s loss of control over drug use, 2) a
patient’s compulsive use of the drug, and 3) continued
use of the drug despite evidence of harm to the pa-
tient.49 Care must be taken with the use of opioids in
patients who are addicted to other drugs and guide-
lines have been established for their use.50 Confusion
over drug-seeking behavior in people with pain has
resulted in the definition of the syndrome called pseu-
W: Cancer

doaddiction. This syndrome refers to ‘‘drug-seeking’’
behavior by patients in their search for adequate pain
relief and is the direct result of inadequate pain man-
agement.51
Many of the barriers to the provision of end of life
care are consistent with those observed with pain and
can be considered to relate to barriers within the sys-
tem, within patients, and with health care providers.
In the U.S., the hospice movement grew as an alterna-
tive to mainstream medicine’s approach to end of life
issues. This has resulted in a lack of integration of
end of life care within most health care systems. The
Medicare benefit was introduced in 1982 and delivers
a per diem payment to licensed hospice providers. It
is envisaged in the Medicare Hospice Act that patients
with õ6 months to live because of a ‘‘terminal’’ illness
will be managed at home and thus avoid the use of
expensive inpatient care. Miller and Mike documented
a number of constraints of the Medicare Hospice Ben-
efit.52 Although the provision that almost all care be
provided in the home is a noble one, with many people
wishing to die at home, the need for a primary care-
giver for these patients almost has become a require-
ment of the provision of hospice care. However, 30%
of the elderly in the U.S. currently are estimated to be
living alone (i.e., without a primary caregiver) and
many of these individuals are women. For those who
do not live alone, many patients’ primary caregivers
are female (72%) and caring for their male partner
results in an increased demand on these women who
may have other responsibilities within the community.
The necessity of a caregiver is a hidden cost of the
Medicare Hospice Program and its provision of end
of life care, which can be intensive in its use of clinical
resources to ensure appropriate symptom manage-
ment. Some hospices will in fact deny admission to
patients who do not have a primary caregiver in the
home. This in turn places increasing demands on fam-
ily support. Patients may feel that they are unnecessar-
ily burdening their family, particularly if family mem-
bers live some distance away or have family and work
commitments. Already strained relationships within
families may be tested further as an elderly parent
approaches the end of life.
Miller and Mike suggest that other barriers exist
to the provision of hospice services within the home.52
There has been low utilization of hospice by people
of color, possibly due to cultural issues, inadequate
provision of services, or again the lack of primary care-
givers, resulting in low admission rates. The Medicare
Hospice Act in the U.S. has strong requirements for a
Medicare license, making provision of hospice services
in rural areas difficult. Hospices are expected to pro-
vide nursing, social work, volunteer support, and be-
/ 7b71$$ge11 09-08-97 14:43:49 cana
Palliative Medicine in the Elderly/Cleary and Carbone 1345
reavement counseling. Hospice workers are expected
to work as a multidisciplinary team comprised of phy-
sicians, nurses, social workers, chaplains, and bereave-
ment workers, services that may be difficult to obtain
in many rural communities. Even if these services be-
come centralized, the long distances required to be
traveled by the hospice workers are another difficulty
in the provision of hospice care.
For a patient to be certified for hospice care, the
attending physician must agree and communicate to
the patient that he or she has an estimated life span
of õ6 months. The estimation of life span is indeed
difficult to make in many cancer patients and may
remain a barrier to hospice care or result in the late
referral of patients. The estimation of life span often
is more difficult with noncancer patients. Often there
are errors in the prediction of life span, and recent
efforts within the U.S. to detect overpayment within
the hospice system may provide another disincentive
to the referral to hospice of cancer patients. Funding
mechanisms with health maintenance organizations,
insurance companies, and other health care organiza-
tions are of further concern and can make the provi-
sion of services difficult for hospice providers.
Palliative Medicine Education
Education in palliative medicine and end of life issues
must be viewed as an important part of the education
of health care professionals, especially those who will
care for the elderly. Efforts are underway to ensure
that medical students and other health care profes-
sionals are educated in the area of pain and end of
life issues. Canada, in particular, has a medical school
curriculum for palliative medicine.3 Aspects of end of
life issues are being addressed within the curriculums
of different medical schools within the U.S.53,54 Differ-
ent organizations within the healthcare system also
are addressing these issues. The American Board of
Internal Medicine has published a detailed review of
the subject.55 The American Society of Clinical Oncol-
ogy stipulates that trainees in general internal medi-
cine exposed to medical oncology understand the
principles of chronic pain management and other
forms of symptom control.56 Trainees should be famil-
iar with the use of opioid analgesics and adjective
medications and with the management of their toxici-
ties. Trainees also should understand the principles of
the care of terminally ill patients, including hospice
programs and the medical and ethical issues associ-
ated with fatal disease.
One of the difficulties faced in reaching this goal
is the education of those who are the clinical teachers
and role models of the current students and residents.
Many of these health care professionals have not been
W: Cancer
1346 CANCER October 1, 1997 / Volume 80 / Number 7
educated in these methods and lack, at their own ad-
mittance, knowledge of the principles and methods
of palliative medicine, particularly knowledge of pain
control. This creates difficulties when the classroom
education on death and dying and the clinical experi-
ence are vastly different. Much greater effort needs
to be expended to ensure that the medical culture is
conducive to symptom management and end of life
care.
Conclusions
The practice of oncology is an issue that incorporates
geriatric medicine. The management of symptoms is
not limited to terminally ill patients. Palliation extends
from the initial care in seeking a cure to the final hours
of a patient’s life. The continuation of this care, from
cure to prolongation of survival to palliation, needs to
stressed both in clinical practice and in education.
Both oncology training and geriatric training must in-
clude adequate exposure to palliative and hospice care
to ensure that symptom management is given the im-
portance in patient care that cancer patients know it
deserves.
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