2012 EDUCATIONAL BOOK - American Society of Clinical Oncology

OLDER PATIENTS WITH ADVANCED CANCER
atric oncology consultative service can help provide geriatric
assessment.
Screening for Impairments in the Oncology Clinic
Several screening tools have been evaluated in oncology
clinical care and research. The Vulnerable Elders Survey-13
(VES-13) is a self-administered survey that consists of one
question for age and an additional 12 items assessing
self-rated health, functional capacity, and physical performance.
11 In 400 community-dwelling older adults, increasing
VES-13 scores strongly predicted death and functional
decline. 12 In a national cohort, a high proportion (45.8%) of
elders with a history of cancer also scored as “vulnerable”
on the VES-13. 3 Luciani and colleagues conducted a study in
a population of 419 patients age 70 and older with a history
of any type of solid or hematologic cancer; 13 the sensitivity
and specificity of VES-13 was 87% and 62%, respectively,
compared with that of the CGA.
The Groningen Frailty Indicator (GFI) is a 15-item survey
that includes questions focusing on mobility/physical fitness,
vision/hearing, nutrition, comorbidity, cognition, and psychosocial
health. 14 The GFI score has been shown to correlate
moderately with CGA results. 15 In a study by Aaldriks
and colleagues, the mortality rate after initiation of chemotherapy
was increased for patients with higher baseline GFI
scores. 16 The GFI has also been shown to be predictive of
outcome in older patients with non-small cell lung cancer
treated with platinum-based doublet chemotherapy. 17
The G8 is an eight-item questionnaire designed to assess
domains of nutrition, mobility, cognitive deficit, polypharmacy,
age, and self-perceived health status. Soubeyran and
colleagues recommend a score of 14 as a predictor of CGA
deficits (90% sensitivity and 60% specificity). 18 In one study,
sensitivity of the G8 for identifying deficits in older patients
with cancer was found to be superior to that of the VES-13. 18
Because these results have not been consistent, screening
tools should not serve as a substitute for a full CGA.
However, if a full CGA cannot be undertaken, screening
tools may serve as a way to capture some important information
within geriatric domains.
Multidisciplinary Approach to Care
A few studies have demonstrated that combining geriatric
and oncologic approaches can affect treatment decision making
for patients with advanced cancer. In the ELCAPA
study, a geriatrician performed an extensive CGA and
proposed a geriatric intervention plan for older patients with
cancer. 19 After the CGA, the initial cancer treatment plan
was modified for 78 (20.8%) of 375 patients, usually to
decrease treatment intensity. In another study of 161 patients
(more than 50% of whom had advanced cancer),
cancer treatment was changed in 49% of patients. 20 In a
pilot study, Horgan and colleagues demonstrated that although
most eligible older patients were not referred for
geriatric assessment, when such assessment was done, the
results guided initial decision making. 21 More data are
necessary to determine whether CGA and interventions can
improve outcomes. It is likely that support from multidisciplinary
expertise, including social work, physical therapy,
occupational therapy, and nutrition can help develop CGAguided
interventions for an at-risk older adult with cancer.
For example, review of medication usage by a pharmacist
can decrease suboptimal prescribing and potentially lead to
a decrease of adverse drug events. 22
Dosing Considerations for Older Patients with
Advanced Cancer
Age-related physiologic changes and comorbid disease can
increase the risk of chemotherapy toxicity. The balance
between risk of treatment and potential benefit is particularly
challenging when treating with noncurative intent.
With respect to treatment characteristics, both standard
dosing of chemotherapy and polychemotherapy have been
associated with increased toxicity among older patients with
cancer. 9 Dose modification, therefore, is one consideration
for treatment planning to minimize the negative consequences
of toxic therapies. Given the paucity of clinical trial
data specific to older patients, there are more questions than
answers regarding dose-modification strategies, particularly
in the setting of first-line treatment for patients with advanced
cancer.
How Common Is Dose Modification for Older Adults
with Advanced Cancer?
Although several large population-based studies have
shown increased age as a risk factor for lower relative-dose
intensity during adjuvant chemotherapy, few data have
been collected in the metastatic setting. In a retrospective
single-insitution study of older patients (mean age, 74.6
years, ECOG score, 0–2) with advanced cancer, 44% had a
dose modification either at initiation of treatment or because
of toxicity. 23 Gajra and colleagues studied factors associated
with primary reduction of chemotherapy dosing during the
first course of treatment among older adults receiving palliative
chemotherapy in a secondary analysis of a multisite
observational study. 24 Almost one-third (29%) of the 319
patients had a primary reduction of chemotherapy dosing.
Older age, a primary diagnosis of lung cancer, and comorbid
conditions were the factors independently associated with a
reduction in this cohort.
Indications for Dose Adjustment Related to
Aging Physiology
Physiologic changes associated with aging have implications
for chemotherapy toxicity among older adults. Aging is
associated with decreased intestinal absorption, changes in
volume of distribution, decreased hepatic metabolism, and
impaired renal excretion. The degree to which these changes
have clinical significance can vary greatly within an older
population. Among the changes, a change in renal function
is the most well described and needs to be accounted for
in dosing considerations. Many chemotherapy drugs are
cleared through the kidneys and it is well-documented that
serum creatinine can provide a substantial underestimation
of renal function in older adults. A creatinine clearance
should be calculated for all older adults before chemotherapy
is initiated, to inform dose adjustment for drugs cleared
through the kidneys. Multiple guidelines provide specific
recommendations for renal dose adjustment, including a
position paper published by the International Society of
Geriatric Oncology (SIOG). 25
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