GERIATRIC ONCOLOGY (TM WILDES, SECTION EDITOR)

Colon Cancer in Older Adults: A Primer for Geriatricians

Tina Hsu & Efrat Dotan

# Springer Science+Business Media New York 2014

Abstract Colon cancer is one of the most common malig-nancies affecting older adults. Studies suggest that older adultsare less likely to receive standard treatments, such as curativesurgery or chemotherapy, compared to their younger counter-parts, despite evidence suggesting that fit older adults deriveequal benefit. The patient’s overall health, life expectancyfrom non-cancer conditions, and personal preferences areimportant considerations in decisions with regard to coloncancer screening and management of early-stage or metastaticdisease. Geriatricians can help oncologists better understandan older adult’s overall health and life expectancy from a non-cancer point of view and can help elucidate patient goals ofcare, advocating for screening and chemotherapy in those whoare healthy enough, and helping to prioritize goals of carewhen patients have other life-limiting illnesses that may pre-clude cancer treatment. This manuscript will attempt to pro-vide practicing geriatricians with evidence-based data regard-ing the management of colon cancer in older adults.

Keywords Colon cancer . Older adults . Elderly . Geriatric .

Screening . Adjuvant chemotherapy . Early-stage coloncancer . Chemotherapy .Metastatic colon cancer

Introduction

Colon cancer (CC) is a common cancer among older adults.The median age of patients with newly diagnosed CC is71 years of age, affecting 1 in 22 men and 1 in 24 womenover the age of 70 [1•]. Furthermore, CC is the second mostcommon cancer in those aged 85 and older [2]. The number ofcases is expected to rise with the aging of the population. Inthe past two decades there have been significant advances inthe management of CC, with the introduction of many novelagents to add to the treatment arsenal (Fig. 1, Table 1). Manyof these therapies are effective and can be safely administeredin older patients, and their use is supported by data fromelderly-specific clinical trials. Geriatricians should have anunderstanding of which patients should receive screening forCC, as well as a working knowledge of treatment approachesand when to refer patients to an oncologist for treatment.Knowledge of treatment approaches will help geriatriciansprovide patients with the guidance and support that they seekin making these difficult treatment decisions, and it will alsoenable them to better guide patients and oncologists in deter-mining the appropriate treatment approach based on the pa-tient’s overall health and preferences.

Colorectal Cancer Screening in Older Adults

Colon cancers typically develop over 10–15 years from pre-malignant lesions (adenomatous polyps). Removal of polypshas been shown to reduce the incidence of CC, providing agood rationale for screening [3]. Several advisory committees,including the U.S. Preventive Services Task Force (USPSTF),American Cancer Society, and Canadian Cancer Society, rec-ommend screening beginning at age 50 in adults at averagerisk of colorectal cancer [4–6]. Screening modalities includethe use of fecal occult blood testing (FOBT), sigmoidoscopy,

T. HsuDepartment of Medical Oncology, City of Hope ComprehensiveCancer Center, 1500 E. Duarte Rd, Duarte, CA 91010, USAe-mail: tina.hsu@medportal.ca

E. Dotan (*)Department of Medical Oncology, Fox Chase Cancer Center, 333Cottman Avenue, Philadelphia, PA 19111, USAe-mail: efrat.dotan@fccc.edu

Curr Geri RepDOI 10.1007/s13670-014-0087-4

and colonoscopy. The American and Canadian CancerSocieties also include fecal immunochemical testing (FIT) asa screening option.

Screening patients between the age 50 and 75 who are ataverage risk of developing CC is generally accepted.Screening in older adults age 75 and over, as well as thosewith comorbidities and poor functional status, is less welldefined. Adults age 75 and older represent a small percentageof those included in CC screening trials, requiring clinicians toextrapolate data from the results for younger adults. TheUSPSTF recommends against screening adults older than85 years, while the American and Canadian CancerSocieties do not have a recommended age at which to discon-tinue screening. A study by Ko and Sonneberg demonstratedthat there can be considerable heterogeneity in risks andbenefits of screening based on age, life expectancy, andscreening strategy [7••], and therefore, age alone is not asufficient determinant. Important factors to consider whendetermining whether a patient should undergo screening arepotential benefit, potential harm, and patient preference.

The higher prevalence of CC with increasing age wouldseem to suggest a benefit for screening among older adults.However, with aging, there is a greater prevalence of comor-bid conditions and competing causes of death, which maymoderate benefits associated with screening. One cross-sectional study that compared the benefit of colonoscopy inpatients ≥80 years of age versus those aged 50–54 yearsfound a higher prevalence of CC (28.6 % vs. 13.8 %) in olderadults, but a smaller average gain in life expectancy (0.13 vs.0.85 years) in older compared to younger patients undergoingscreening colonoscopy [8•].

Age and the presence of comorbidities may also increasethe likelihood of harm from screening. A retrospectivepopulation-based study found a greater risk of complications

from colonoscopy, such as bleeding and perforation, associat-ed with advanced age and increased comorbidity [9], and therisk was even higher in patients who had polyps removed.Another study found that the highest risk was associated withcolonoscopy-based screening strategies, followed by flexiblesigmoidoscopy, and FOBT [7••]. One of the greatest harmsof screening, however, is the detection and diagnosis ofcancers that are not life-limiting and would never havebecome clinically significant in the patient’s lifetime (10).Thus, consideration of a patient’s life expectancy is essentialwhen deciding whether to screen for CC. By utilizing theframework proposed by Walter and Covinsky on screeningfor cancer in older adults, clinicians can estimate a patient’sexpected life expectancy based on age and health status [10••].As randomized trials of CC screening generally do not dem-onstrate an improvement in CC survival until at least fiveyears after screening is begun, patients who have a life expec-tancy of less than five years should not be screened [11, 12]. Inaddition, patients with conditions that would preclude treat-ment of a diagnosed CC should not undergo screening. Lastly,patient preference for screening and willingness to undergotreatment is also an important consideration when weighingthe benefits versus the risks of screening.

Management of Early-stage Colon Cancer Among OlderAdults

Surgery

Surgical resection of localized CC remains the mainstay oftreatment, curing 85–90 % of patients with stage I-II (lymphnode-negative) CC and 45–50 % with stage III (lymph node-positive) CC [13, 14]. Older patients, however, are less likely

Fig. 1 Summary of theadvancements in therapy ofmetastatic colon cancer over thelast two decades. The blue arrowsrepresent the data regardingsurvival with each therapy in thegeneral patient population. Thegray arrows represent the dataregarding survival with eachtherapy among older adults withmetastatic colon cancer. Thedarker arrows represent data fromelderly-specific prospectiveclinical trials, while the lightgray arrows represent data fromretrospective reviews or post hocanalyses

Curr Geri Rep

to be offered curative surgery for compared to their youngercounterparts [15–17, 18••], which may be due to concerns ofincreased post-surgical morbidity. The data in the literaturewith regard to perioperative complication rates among olderadults reflects mixed results. Some studies report higher ratesof postoperative surgical (e.g., ileus, peritonitis, abscess, andwound infection) and systemic (i.e., cardiovascular, renal, orrespiratory) complications in older adults, while others dem-onstrate only minor increases in specific risks (e.g., postoper-ative bleeding) [16, 18, 19•, 20–22]. Emergent or urgentsurgical procedures have been shown to be associated withhigher peri-operative risk among older adults [16–18].Overall, over the last decade, postoperative mortality hasdecreased by 6.4–9.1 % each year, with the greatest improve-ment seen in adults aged 85 and older [19•]. This may be as aresult of greater use of laparoscopic procedures, which areassociated with lower peri-operative risk [23]. Clearly, patientselection and surgical expertise are factors that affect thedegree of peri-operative risk for older adults.

Careful pre-surgical evaluation and increased use of elec-tive surgeries may mitigate the risk the morbidity and mortal-ity associated with CC resection in older adults. In addition,utilization of a comprehensive geriatric assessment (CGA)may help identify patients at high peri-operative risk. Studiesare ongoing to develop and validate a tool specifically forolder patients that could be used preoperatively. One such toolis the Preoperative Assessment of Cancer in the Elderly(PACE), which combines a CGA with additional measuresof fatigue, performance status, and the American Society ofAnesthesiologists (ASA) score [24].

In summary, surgical resection of early-stage CC is consid-ered a curative treatment and should be offered to patientsregardless of age. These surgeries can be performed safely,even in patients 80 years and older. Geriatricians must advo-cate for curative surgery for their fit older patients with local-ized CC, as well as the assessment and optimization of thepatient’s overall health prior to the surgical procedure.

Adjuvant Chemotherapy

Even with resection of CC, there remains a risk of recurrence,with a 15–25% and 40–55% chance of recurrence within fiveyears in patients with stage II (lymph node-negative) and stageIII (lymph node-positive) CC, respectively [13, 14, 25, 26].The purpose of adjuvant chemotherapy is to decrease this risk,and the decision to administer adjuvant chemotherapy is basedupon the risk of recurrence and effectiveness of the treatmentweighed against potential toxicities as well as patient prefer-ence and ability to tolerate therapy.

Patients with cancer involving the lymph nodes (stage III)are at high risk of recurrence. Other features associated withhigh risk include removal of fewer than 12 lymph nodes,tumors that perforate the visceral peritoneum or adjacent

organs (T4), presentation with bowel perforation or obstruc-tion, high pathologic grade, and lymphovascular invasion.Single-agent chemotherapy with 5-fluorouracil (5-FU) or cap-ecitabine (oral formulation of 5-FU) (Table 1), given for sixmonths following surgical resection, reduces the relative riskof recurrence by 38–48 % in patients with stage III CC [27].The addition of oxaliplatin to 5-FU further lowers the absoluterisk of recurrence by up to 6 %, and improves six-year overallsurvival by up to 2.5 % [28, 29]. Patients with resected stageIII CC who are fit enough to undergo chemotherapy aretherefore generally offered adjuvant combinationchemotherapy.

The role of adjuvant chemotherapy in the setting of stage IICC is more controversial, and in the setting where used, ittypically involves single-agent chemotherapy. Several pooledanalyses, including a Cochrane review, suggest that adjuvantchemotherapy may decrease the risk of recurrence of stage IIdisease at five years by 3–4 % [27, 30–32]. Only one of thesestudies, however, showed an improvement in survival at fiveyears with the addition of chemotherapy to surgery [32]. Dueto the limited improvement in outcomes with this treatment,chemotherapy is not routinely administered in patients withstage II CC, although it is sometimes considered in patientswith tumor features that place them at higher risk of recur-rence. Furthermore, because the benefit of chemotherapy inpatients with stage II CC is predominantly to lower the likelihoodof cancer recurrence, with little impact on survival, individualconsiderations such as overall health, risk of toxicity, andpatient preference play a more prominent role in the decisionto undergo therapy.

The recommended chemotherapy regimens in the adjuvantsetting include monotherapy with 5-fluorouracil (5-FU) orcapecitabine, or the combination of one of these drugs withoxaliplatin (Table 1). Studies have shown that fit older adultsdo not experience a greater degree of side effects comparedwith their younger counterparts, with the exception of anincreased risk of myelosuppression [33••, 34••, 35••].Although patients 65 or older are more likely to discontinuechemotherapy earlier than planned (40% vs. 25%) [36], olderadults continue to derive a similar benefit from adjuvantchemotherapy as younger patients [36].

Side effects that are particularly relevant in older adultsinclude cardiotoxicity and peripheral neuropathy.Cardiotoxicity related to 5-FU/capecitabine administration isa rare yet significant side effect in older adults. It typicallypresents as angina or myocardial infarction with EKG chang-es, and is generally reversible with discontinuation of chemo-therapy. The incidence of cardiotoxicity ranges from 1.6–19 % [37–41], with greater risk among patients with a historyof coronary artery disease [37, 42]. Peripheral neuropathyoccurs in over 90 % of patients treated with oxaliplatin, with10 % of patients experiencing functional limitations [28, 29].Although the severity of peripheral neuropathy typically

Curr Geri Rep

Tab

le1

Drugs

used

inthemanagem

ento

fcoloncancer

Drug

Modeof

Adm

inistration

Mechanism

ofAction

Com

mon

SideEffects

Serious

Side

Effects

Geriatric-Specific

Consideratio

nsIm

portantD

osing

Consideratio

ns

Chemotherapy

5-Fluorouracil

(5-FU)

Intravenous

InhibitsDNAandRNA

synthesis

Mucositisdiarrhea

Nausea/

vomiting

Myelosuppression/

infectionHand-food

syndrome(palmar-plantar

erythrodysesthesia)

Cardio-toxicity

(angina,

MI,CHF,arrhythm

ias)

Riskof

dehydrationdueto

mucositisanddiarrhea

Patientswith

pre-existing

cardiacdiseaseathigher

riskof

cardio-toxicity[37,42]

Hepaticmetabolism

Significantd

rug

interactions:C

oumadin,

Phenytoin

Capecitabine

(oral5

-FU)

Oral

InhibitsDNAand

RNAsynthesis

Hand-foot

syndrome

(palmar-plantar

erythrodysesthesia)

Diarrhea

Cardio-toxicity

(angina,

MI,CHF,arrhythm

ias)

Riskof

dehydrationdueto

mucositisanddiarrhea

Severe

hand-footsyndrom

emay

interferewith

patient

functio

n(e.g.,walking)

Patientswith

pre-existin

gcardiacdiseaseathigher

risk

ofcardio-toxicity

Renally

clearedSignificant

drug

interactions:

Coumadin

Oxalip

latin

Intravenous

InhibitsDNAreplication

Acute(24-48

hpost-infusion)

cold-induced

neuropathy

(perioral,laryngeal,peripheral

neuropathy)Chronic

peripheralneuropathy

Myelosuppression,

infectionNausea/vomiting

Chronicperipheralneuropathy

Nephrotoxicity

Riskof

persistentperipheral

neuropathy

increaseswith

cumulativedoses.May

resultinfunctional

limitations

andincreased

iskof

falls

Renally

cleared

Irinotecan

Intravenous

InhibitsDNA

replication

Diarrhea,abdominalcram

psNausea/vomiting

Fatig

ueNeutropenia,infectio

n

Diarrheaisvery

common,

placingpatientsathigh

risk

ofdehydration

Hepaticmetabolism

BiologicAgents(m

onoclonalantibodiesandtyrosine

kinase

inhibitors)

Bevacizum

abIntravenous

Inhibitsangiogenesis

HypertensionProteinuria

Delayed

wound

healing

Arterialand

venous

thromboem

bolic

events

Bow

elobstruction

Gastrointestin

alperforation

Older

adultsathigher

risk

ofarterialthromboem

bolic

events(e.g.,myocardial

infarctio

nor

stroke

[69,70,73]

Cetuxim

ab/

Panitumum

abIntravenous

Inhibitscelldivision

byblocking

signaling

thatoccursthrough

Epiderm

alGrowth

FactorsReceptor(EGFR)

DiarrheaAcneiform

rash

(face,torso)

Hypom

agnesemia

Hypersensitivity

reactio

n

Aflibercept

Intravenous

Inhibitsangiogenesis

Neutropenia,infectio

nFatig

ueMucositis,

diarrhea

Hypertension

Proteinuria

Delayed

wound

healing,

Bleeding/hemorrhage

Gastrointestin

alperforation

Arterialand

venous

thromboem

bolic

events

Older

adultsathigher

risk

ofdehydrationdue

todiarrhea

Curr Geri Rep

lessens gradually with time, 1 % of patients experiencefunction-limiting peripheral neuropathy beyond one year aftercompletion of oxaliplatin-containing chemotherapy. This canhave profound implications in older adults, as patients withperipheral neuropathy are at higher risk of falling [43•].

Older adults are under-represented in prospective clinicaltrials evaluating adjuvant chemotherapy, making it difficult toextrapolate data. A large pooled analysis of 3,351 patientssuggests that older adults treated with 5-FU single-agent che-motherapy derive benefit similar to that seen among youngerpatients [34]. The benefit of adding oxaliplatin to 5-FU che-motherapy in older adults is less clear. While studies suggestthat combination chemotherapy may decrease the likelihoodof recurrence, particularly in the first three years followingdiagnosis, this benefit disappears with longer follow-up, andno improvement in survival is seen [28, 44••, 45••].

Even after comorbidities and health status are taken intoaccount, advanced age is a significant predictor of non-receiptof chemotherapy, [45••, 46–48]. A Surveillance, Epidemiologyand End Results (SEER)Medicare population-based analysis ofpatients with stage III colon cancer reported a precipitous declinein receipt of chemotherapy with advancing age, with only 44 %of older patients evaluated receiving adjuvant chemotherapy[45••, 46]. As 80 % of recurrences occur within the first threeyears post-diagnosis, and 91 % of these patients die within fiveyears, patients with a life expectancy of at least five years maybenefit from adjuvant chemotherapy [49]. Many older patientsin this setting, therefore, should be evaluated and potentiallytreated with adjuvant chemotherapy. Geriatricians are well-versed and ideally positioned to obtain an overall assessmentof a patient’s health, recognize and prioritize health issues, andelicit patient preferences and goals of care. They can utilize theirexpertise to help oncologists better identify patients who maybenefit from adjuvant chemotherapy and can advocate forpatients based upon this assessment.

Treatment of Metastatic Colon Cancer Among OlderAdults

Aswith all other treatmentmodalities, the treatment ofmetastaticcolon cancer (mCC) in elderly patients must be tailored to thepatient’s performance status, comorbidities, and preferences.While cure is rare in this setting, treatments with surgical resec-tion and chemotherapy have shown benefit in survival, quality oflife, and symptom control [50]. Over the past two decades, thesurvival of patients with mCC has improved significantly.Whereas initial reports indicated a 12-month survival benefitfor single-agent 5-FU, the use of multiple chemotherapy andbiologic agents confers a median survival of over 24 months[51–56]. According to recently published elderly-specific ran-domized clinical trials, this data holds true for older patients asT

able1

(contin

ued)

Drug

Modeof

Adm

inistration

Mechanism

ofAction

Com

mon

SideEffects

Serious

Side

Effects

Geriatric-Specific

Consideratio

nsIm

portantD

osing

Consideratio

ns

Regorafenib

Oral

Inhibitsangiogenesis

andtumor

grow

thFatig

ue,anorexiaHand-foot

syndrome(palmar-plantar

erythrodysesthesia);rash

Mucositis,diarrhea

HypertensionAnemia,

thrombocytopenia

Delayed

wound

healing,

bleeding/hem

orrhage

Gastrointestin

alperforation

Cardio-toxicity

(ischemia/

infarctio

n)Hepatotoxicity

/Liver

failu

re

Significantd

rug

interactions:CYP3A

4inducers(e.g.,phenytoin,

carbam

azepine,St.

John’sWort)CYP3

A4

inhibitors(e.g.,

clarith

romycin,

grapefruitjuice)

Curr Geri Rep

well (Figure 1) [57••, 58••]. Furthermore, the widespread use ofsupportive care services has also greatly improved tolerance tothese treatments [59], and many older patients with mCC areable to undergo and derive a benefit from anti-cancer therapy.

A small percentage of patients who have tumors with resect-able metastases affecting a single organ can be cured with acombination of local and systemic therapies. Resection of soli-tary metastases carries a slightly higher morbidity and mortalityrisk in older patients. A study of patients 70 years of age andolder who underwent liver resection for mCC found a higher 60-day postoperative mortality rate (3.8 % vs. 1.6 %; p<0.001) andlower three-year overall survival (57.1 % vs. 60.2 %; p<0.001)among older versus younger patients [60•]. No difference inoverall survival was seen between the subcategories of olderages (70–75 years, 75–80 years, and >80 years). These findingswere confirmed in an analysis of 3,957Medicare enrollees [61•].These data suggest that advanced age should not be viewed as anabsolute contraindication for surgical procedures in themetastaticsetting, although consideration should be given to patient selec-tion and fitness for surgery.

The mainstay of treatment for mCC is chemotherapy. Giventhe multiple drugs available for the treatment of mCC today(Table 1), patients may receive more than three lines of therapyfor their disease [62, 63]. Fit patients are initially treated with acombination of 5-FU, oxaliplatin or irinotecan, and the anti-angiogenesis agent bevacizumab [62]. Approximately two-thirds of mCC patients are also candidates for treatment withanti-epidermal growth factor receptor (anti-EGFR) agents aloneor in combination with chemotherapy. Single-agent therapy or amodified regimen of combination therapy is sometimes used inpatients with comorbidities that preclude specific agents (e.g.,the use of bevacizumab in patients with recent cardiac ische-mia) and/or to improve tolerability in frailer patients. Quality oflife of older patients with mCC may also be preserved byalternating between treatment and treatment-free intervals [64].

Studies suggest that older adults with mCC derive benefitfrom chemotherapy similar to their younger counterparts, withno increase in side effects. Retrospective studies and post hocanalyses of large randomized clinical trials utilizing combinationchemotherapy of 5-FU and oxaliplatin or irinotecan have report-ed comparable efficacy in older versus younger patients, withoutincreased toxicity [33, 65••, 66••, 67, 70••]. These analysesshould be interpreted cautiously however, as they included olderpatients who were fit enough for a clinical trial and may havebeen prone to selection bias in view of their retrospective nature.However, even in patients who are considered too frail to under-go standard full-dose chemotherapy, studies suggest that modi-fied chemotherapy is efficacious and tolerable. The FOCUS 2study, which randomized elderly and frail patients to 5-FU/capecitabinewith andwithout oxaliplatin at 20%dose reduction,reported a median overall survival of 10–12 months, whichrepresents an improvement compared to survival with best sup-portive care (Fig. 1) [58]. Furthermore, 47–65 % of patients

improved global QOL after starting chemotherapy [58]. A sim-ilar study is ongoing to evaluate the combination of 5-FU andirinotecan in patients 75 years and older (FFCD 2001-02 trial).

With the introduction of biologic non-chemotherapeuticagents, the treatment of mCC has changed significantly(Table 1). Bevacizumab, an anti-angiogenic agent, is givenin combination with a chemotherapy backbone such as 5-FUand oxaliplatin or irinotecan. A recently published phase IIIclinical trial investigating adults aged 70 years and olderdemonstrated significantly delayed cancer progression, by anaverage of four months, in patients treated with capecitabineand bevacizumab compared to capecitabine alone [59]. Thiswas associated with an increased risk of severe side effects,consistent with those seen among younger patients receivingbevacizumab (Table 1). However, retrospective studies havesuggested an increased risk of thromboembolic events amongolder patients treated with this agent [65••, 68•• 69, 70••, 71•,72••] . Prospective data is lacking with regard to the efficacyand tolerability of anti-EGFR agents such as cetuximab andpanitumumab (Table 1) among older patients. However, ret-rospective studies have shown similar toxicity profiles andefficacy in older and younger patients who received theseagents [71•, 73–75]. Regorafenib, a multi-kinase inhibitor,and aflibercept, a vascular endothelial growth factor (VEGF)receptor inhibitor, were recently approved for the treatment ofmCC based on clinical benefit seen in large phase III studies[76, 77]. Additional studies are needed to define the role ofthese newer biologic agents among older patients.

A thorough evaluation of a patient’s overall health is impor-tant to identify conditions that can affect treatment outcomes.One study evaluated the predictive value of a geriatric assessmentfor toxicity from an irinotecan-based regimen and found thatpatients with cognitive deficits (MMSE </=27/30) (OR 3.84) orADL dependence (OR 4.67) were more likely to experiencesevere toxicity [78••] . As CGA is rarely conducted in oncologyclinics, and subtle cognitive deficits may be missed, it is impor-tant that geriatricians highlight these deficits for oncologists. Byproviding this important information, geriatriciansmay be able tohelp limit unnecessary adverse events.

Notwithstanding the challenges present in treating older pa-tientswithmCC, large prospective studies have better defined thebenefit of these therapies in this population. However, manyolder adults with mCC still do not receive anti-cancer therapy.In themetastatic setting, Ho et al. reported less than 50% of olderpatients with metastatic CC received systemic palliative chemo-therapy [79]. Data also shows that bevacizumab is used in just athird of older patients who are eligible for this treatment approach[80].While there is a subpopulation of older patient who are bestserved by limiting administration of these toxic therapies due tocompeting causes of death, many older patients are candidatesmany older patients are candidates for these treatments and maybenefit from them. Furthermore, the benefit of systemic therapycan include an improvement in quality of life or symptom control

Curr Geri Rep

[58]. Endpoints such as quality of life or symptom control, whichhave rarely been studied in clinical trials, may be important tostudy given that they have greater clinical significance to olderadults with terminal illness [81]. Given the large number of olderpatients with this illness, ongoing research is needed to continueto help define optimal treatment for older adults with mCC.

Conclusion

Despite the large number of older patients with CC seen inclinical practice, limited prospective data is available to guidedisease management in this patient population. While fit olderpatients are likely to tolerate therapy for CC and derive benefitfrom it, frail patients are more likely to experience unnecessarytoxicity, with limited benefit. Oncologists are faced with thechallenge of differentiating between these two groups, and tai-loring therapy to a patient’s biologic rather than chronologic age.There is increasing evidence that a CGA is useful for identifyingolder adults with cancer who are at higher risk of toxicity, aremore likely to discontinue chemotherapy, and are more likely tosuccumb to cancer early [82–84, 85••] . In addition, CGA oftendetects conditions that otherwise go unnoticed during a standardoncologic assessment [86, 87]. Notwithstanding the growingrecognition of the value of CGA, incorporating it into a busypractice is challenging and impractical for many oncologists.Geriatricians can assist oncologists with this assessment,allowing them to tailor therapy to each individual patient. Withthe aging of the population and increased prevalence of coloncancer in older adults, oncologists and geriatricians will findincreasing opportunity to work together in the clinic and inresearch settings to define the ideal treatment for this patientpopulation.

Compliance with Ethics Guidelines

Conflict of Interest Tina Hsu and Efrat Dotan declare that they have noconflict of interest.

Human and Animal Rights and Informed Consent This article doesnot contain any studies with human or animal subjects performed by anyof the authors.

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19.• Jafari MD, Jafari F, Halabi WJ, Nguyen VQ, Pigazzi A, CarmichaelJC, et al. Colorectal Cancer Resections in the Aging US Population:ATrend Toward Decreasing Rates and Improved Outcomes. JAMASurg. 2014 This study reports the improvement in surgical outcomesamong older colorectal cancer patients, with the greatest improve-ment seen among patients 85 years or older.

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33.•• Goldberg RM, Tabah-Fisch I, Bleiberg H, de Gramont A,Tournigand C, Andre T, et al. Pooled analysis of safety and efficacyof oxaliplatin plus fluorouracil/leucovorin administered bimonthlyin elderly patients with colorectal cancer. Journal of clinical oncol-ogy : official journal of the American Society of Clinical Oncology.2006;24(25):4085-91 This pooled analysis provides data regard-ing the use of 5FU in combination with oxaliplatin among oldercolon cancer patients.

34.•• Sargent DJ, Goldberg RM, Jacobson SD, Macdonald JS, LabiancaR, Haller DG, et al. A Pooled Analysis of Adjuvant Chemotherapyfor Resected Colon Cancer in Elderly Patients. New EnglandJournal ofMedicine. 2001;345(15):1091-7 This is a pooled analysis

evaluating the adjuvant chemotherapy outcomes among older co-lon cancer patients.

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41. Akhtar SS, Salim KP, Bano ZA. Symptomatic cardiotoxicity withhigh-dose 5-fluorouracil infusion: a prospective study. Oncology.1993;50(6):441–4.

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43.• Tofthagen C, Overcash J, Kip K. Falls in persons with chemotherapy-induced peripheral neuropathy. Support Care Cancer: Off J MultinatlAssoc Support Care Cancer. 2012;20(3):583–9. This manuscripts de-scribes the association between chemotherapy induced peripheralneuropathy and falls among older cancer patients.

44.•• McCleary NJ, Meyerhardt JA, Green E, Yothers G, de Gramont A,VanCutsem E, et al. Impact of age on the efficacy of newer adjuvanttherapies in patients with stage II/III colon cancer: findings from theACCENT database. J Clin Oncol: Off J Am Soc Clin Oncol.2013;31(20):2600–6. This study evaluated the benefit of the addi-tion of oxaliplatin to 5FU chemotherapy following resection ofearly stage colon cancer among older patients. The benefit seenwith the addition of oxaliplatin to 5FU in younger patients was notreproduced in the older patient population.

45.•• Sanoff HK, Carpenter WR, Sturmer T, Goldberg RM, Martin CF,Fine JP, et al. Effect of adjuvant chemotherapy on survival ofpatients with stage III colon cancer diagnosed after age 75 years. JClin Oncol: Off J Am Soc Clin Oncol. 2012;30(21):2624–34.PMCID: 3412313 This large retrospective study reports limitedbenefit with the addition of oxaliplatin to 5FU chemotherapy inthe adjuvant setting among older colon cancer patients.

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52. Douillard JY, Siena S, Cassidy J, Tabernero J, Burkes R, BarugelM, et al. Randomized, phase III trial of panitumumab withinfusional fluorouracil, leucovorin, and oxaliplatin (FOLFOX4)versus FOLFOX4 alone as first-line treatment in patients withpreviously untreated metastatic colorectal cancer: the PRIME study.J Clin Oncol: Off J Am Soc Clin Oncol. 2010;28(31):4697–705.

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54. Hurwitz H, Fehrenbacher L, NovotnyW, Cartwright T, HainsworthJ, Heim W, et al. Bevacizumab plus irinotecan, fluorouracil, andleucovorin for metastatic colorectal cancer. N Engl J Med.2004;350(23):2335–42.

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57.•• Seymour MT, Thompson LC, Wasan HS, Middleton G, BrewsterAE, Shepherd SF, et al. Chemotherapy options in elderly and frailpatients with metastatic colorectal cancer (MRC FOCUS2): anopen-label, randomised factorial trial. Lancet. 2011;377(9779):1749–59. Elderly specific prospective clinical trial randomizingolder/frail patients between single agent 5FU/Capecitabine versusin combination with dose reduced oxaliplatin.

58.•• Cunningham D, Lang I, Marcuello E, Lorusso V, Ocvirk J, ShinDB, et al. Bevacizumab plus capecitabine versus capecitabine alonein elderly patients with previously untreated metastatic colorectalcancer (AVEX): an open-label, randomised phase 3 trial. LancetOncol. 2013;14(11):1077–85. This elderly specific prospective ran-domized clinical trial demonstrated significant improvement inoutcomes with the addition of bevacizumab to capecitabine in thefront line setting of metastatic colon cancer among older patients.

59. Balducci L. Supportive care of elderly patients with cancer. SupportCancer Ther. 2005;2(4):225–8.

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61.• Robertson DJ, Stukel TA, Gottlieb DJ, Sutherland JM, Fisher ES.Survival after hepatic resection of colorectal cancer metastases: anational experience. Cancer. 2009;115(4):752–9. This study pro-vides important information regarding the outcomes of older pa-tients undergoing surgical resection of colon cancer metastases.

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64. Maindrault-Goebel F, Lledo G, Chibaudel B, Mineur L, Andre T,Bennamoun M, et al. Final results of OPTIMOX2, a large random-ized phase II study of maintenance therapy or chemotherapy-freeintervals (CFI) after FOLFOX in patients with metastatic colorectalcancer (MRC): A GERCOR study. Journal of Clinical Oncology,ASCO Annual Meeting Proceedings Part I 2007;Vol 25( No. 18S(June 20 Supplement)):Abstract # : 4013

65.•• Folprecht G, Cunningham D, Ross P, Glimelius B, Di Costanzo F,Wils J, et al. Efficacy of 5-fluorouracil-based chemotherapy inelderly patients with metastatic colorectal cancer: a pooled analysisof clinical trials. Ann Oncol: Off J Eur Soc Med Oncol / ESMO.2004;15(9):1330–8. This pooled analysis supports the use of 5FUbased chemotherapy among older patients with metastatic coloncancer.

66.•• Feliu J, Salud A, Escudero P, Lopez-Gomez L, Bolanos M, GalanA, et al. XELOX (capecitabine plus oxaliplatin) as first-line treat-ment for elderly patients over 70 years of age with advancedcolorectal cancer. British journal of cancer. Br J Cancer.2006;94(7):969–75. This study demonstrates the benefit of thecombination of capecitabine and oxaliplatin for first line therapyof patients over the age of 70 with metastatic colon cancer.

67. Twelves CJ, Butts CA, Cassidy J, Conroy T, Braud F, Diaz-RubioE, et al. Capecitabine/oxaliplatin, a safe and active first-line regimenfor older patients with metastatic colorectal cancer: post hoc anal-ysis of a large phase II study. Clin Colorectal Cancer. 2005;5(2):101–7.

68.•• Van Cutsem E, Rivera F, Berry S, Cunningham D. Safety andefficacy of bevacizumab (BEV) and chemotherapy in elderly pa-tients with metastatic colorectal cancer (MCRC): Results from theBEAT observational cohort study. Ann Oncol: Off J Eur Soc MedOncol / ESMO. 2009;20 Suppl 7:PD-0005. This is a report of thetolerance and benefit of bevacizumab among older mCC patientsfrom the BEAT observational cohort study.

69. Hershman DL,Wright JD, Lim E, Buono DL, Tsai WY, Neugut AI.Contraindicated use of bevacizumab and toxicity in elderly patientswith cancer. J Clin Oncol. 2013;31(28):3592–9.

70.•• Souglakos J, Pallis A, Kakolyris S, Mavroudis D, Androulakis N,Kouroussis C, et al. Combination of irinotecan (CPT-11) plus 5-fluorouracil and leucovorin (FOLFIRI regimen) as first line treat-ment for elderly patients with metastatic colorectal cancer: a phaseII trial. Oncology. 2005;69(5):384–90. The study reports the out-comes and toxicity of the use of combination chemotherapy with5FU and irinotecan among older patients with metastatic coloncancer.

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72.•• Kozloff M, Sugrue MM, Berlin J, Flynn PJ, Kabbinavar F, SargentD, et al. Safety and effectiveness of bevacizumab (BV) and chemo-therapy (CT) in elderly patients (pts) with metastatic colorectalcancer (mCRC): Results from the BRiTE Prospective CohortStudy. 2008 Gastrointestinal Cancers Symposium.Abstract 454This is a report of the tolerance and benefit of adding bevacizumabto chemotherapy among older mCC patients, dat from teh BRiTEprospective cohort study.

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79. Ho C, Ng K, O'Reilly S, Gill S. Outcomes in elderly patients withadvanced colorectal cancer treated with capecitabine: a population-based analysis. Clin Colorectal Cancer. 2005;5(4):279–82.

80. Pasetto LM, Falci C, Sinigaglia G, Brandes AA, Monfardini S.How many colorectal cancer (CRC) patients older than 70 yearsmay be safely treated with bevacizumab? Journal of clinical oncol-ogy : official journal of the American Society of Clinical Oncology.2006;24(18S):Abstract # 13589.

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