NcXHF

STUART M. LICHTMAN
an outcome of cancer treatment. Chemotherapy might not
only affect functional status in metastatic incurable cancer,
but might also result in changes of functional status in patients
whose cancer may be curable, such as patients with
breast or colorectal cancer receiving adjuvant chemotherapy
and patients with lymphoma.
SURVIVORSHIP
Although not usually part of standard clinical trial design, the
issues of survivorship in older survivors of cancer need to be
explored. 35-37 As a result of increased utilization of screening
and earlier detection of common cancers (i.e., breast, colorectal,
and prostate), coupled with incremental improvements
in cancer treatment and supportive care, the number
of cancer survivors in the United States has increased from
approximately 3 million in 1970 to almost 14 million in 2014.
Patients age 70 and older account for 46% of all survivors. 38
Survivorship has become a separate, but related, discipline of
oncology that requires both expertise and the infrastructure
to provide optimal care for cancer survivors. Cancer survivors
have unique problems. Pre-existing comorbid issues are
often compounded by the residual toxicity of cancer treatment
and the possibility of late adverse effects. There are also
emotional issues regarding survivorship. The Institute of
Medicine has issued recommendations regarding cancer survivorship
programs and a number of centers of excellence
have been developed to evaluate different survivorship clinical
models. These are focusing on many different areas, including
behavioral interventions, nutritional interventions,
cancer screening, studies of morbidity, physical activity, sexual
function, and fatigue. 39-41
DOSE-LIMITING TOXICITY
Schedule changes may alter the toxicity profıle of chemotherapy
in an older population. For example, weekly paclitaxel
versus paclitaxel and bolus 5-fluorouracil every 3 weeks versus
infusional 5-fluorouracil may show differences in toxicity.
The commonly used toxicity criteria may not be adequate
to assess adverse events in older patients. Neuropathy assessment
should include evaluation of functional decline
or falls. The reports of studies should be age-specifıc. Most
trials only report grade 3 or 4 toxicity, even though grade 2
toxicity often has clinical relevance. Reporting the full
spectrum of toxicity for a clinical trial will help clinicians
make treatment decisions. Studies of new agents in predetermined
stages of aging (i.e., frail or vulnerable) or in patients
with specifıc common comorbidities or functional
impairments would be invaluable. Common Terminology
Criteria for Adverse Events (CTCAE) version 4 does incorporate
functionality in the grading and could be applied to
geriatric patients.
PHASE I STUDIES
Only a limited number of phase I trials have involved older
patients, despite the fact that the heterogeneity of this population
limits the applicability of results from phase I studies
performed in fıt, younger patients. 42 Traditionally, during
the phase I investigation, acute toxicities are identifıed and
the potential duration and reversibility of the toxicities are
defıned. Selecting appropriate patients to accurately evaluate
toxicity in a phase I clinical investigation is extremely important.
Typically, patients included in phase I trials have a good
performance status and normal organ function. As a result,
entry criteria often exclude older patients from dose-fınding
trials. However, studies in the older person could be defıned
differently from what has been done historically. For example,
after a phase I dose is determined, older patients with
varying degrees of functional impairment or comorbidities
can be treated to determine whether the dose is appropriate.
ASCO has published a position paper on the importance of
phase I studies with suggestions to enhance accrual. They
mention the critical role that Medicare has in supporting
these trials and by inference, increasing the participation of
older patients. Although the position paper specifıcally cites
issues regarding pediatric patients, there is no specifıcity with
respect to older people. 43
Disclosures of Potential Conflicts of Interest
Relationships are considered self-held and compensated unless otherwise noted. Relationships marked “L” indicate leadership positions. Relationships marked “I” are those held by an immediate
family member; those marked “B” are held by the author and an immediate family member. Institutional relationships are marked “Inst.” Relationships marked “U” are uncompensated.
Employment: None. Leadership Position: None. Stock or Other Ownership Interests: None. Honoraria: None. Consulting or Advisory Role: Stuart M.
Lichtman, Bayer, Icore Health Care. Speakers’ Bureau: Stuart M. Lichtman, Plexus Communications. Research Funding: None. Patents, Royalties, or
Other Intellectual Property: None. Expert Testimony: None. Travel, Accommodations, Expenses: Stuart M. Lichtman, Bayer. Other Relationships: None.
References
1. Carbone PP, Yancik R (ed). Perspectives on prevention and treatment of
cancer in the elderly. New York, NY: Raven Press; 1983.
2. Kennedy BJ. Aging and cancer. J Clin Oncol. 1988;6:1903-1911.
3. Hutchins LF, Unger JM, Crowley JJ, et al. Underrepresentation of patients
65 years of age or older in cancer-treatment trials. N Engl J Med.
1999;341:2061-2067.
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