Treatment of Advanced Non–Small-Cell Lung Cancer in Special Populations

September 1, 2004
Wade Smith, MD

,
Michael Fanucchi, MD

Oncology, ONCOLOGY Vol 18 No 11, Volume 18, Issue 11

Only a minority of elderly patientswith advanced non–small-cell lung cancer(NSCLC) have been offered palliativechemotherapy, as indicated by clinicalsurveys beginning in the 1980s.Lilenbaum’s thorough review of thetreatment of locally advanced and metastaticNSCLC studies in two specialpopulations (elderly and Eastern CooperativeOncology Group [ECOG]performance status [PS] 2 patients)highlights a new trend seen with theadvent of better-tolerated chemotherapyregimens.

Only a minority of elderly patientswith advanced non-small-cell lung cancer(NSCLC) have been offered palliativechemotherapy, as indicated by clinicalsurveys beginning in the 1980s.Lilenbaum's thorough review of thetreatment of locally advanced and metastaticNSCLC studies in two specialpopulations (elderly and Eastern CooperativeOncology Group [ECOG]performance status [PS] 2 patients)highlights a new trend seen with theadvent of better-tolerated chemotherapyregimens.Key Studies
For patients older than age 70 yearswith no major comorbidities, the authorrefers to US cooperative groupstudies to justify the use of a platinum-based doublet-as would be usedin the younger patient population.Alternatively, elderly patients withsevere comorbidities and a lowerperformance status could be treatedwith single-agent therapy, such as vinorelbine(Navelbine) or gemcitabine(Gemzar), as shown in Gridelli's ElderlyLung Cancer Vinorelbine ItalianStudy (ELVIS) that assessed for the first time the benefit of a newer chemotherapyagent in older patients.[1]Also of note, given that the majorityof elderly lung cancer patients presentwith unresectable disease, Schild andcolleagues discovered that fit elderlypatients with locally advancedNSCLC also enjoyed a survival advantagewhen treated with combinedmodalitytherapy.[2]Functional vs Chronologic Age
The decision to treat an elderlyNSCLC patient with palliative chemotherapywill depend more on thepatient's functional age than chronologicage. Lilenbaum recognizes thata favorable functional status portendsa good response to chemotherapy.Functional status is one of severalcomponents that comprise a comprehensivegeriatric assessment.[3] Othersinclude the patient's comorbidmedical conditions, cognition, psychologicalstatus, social functioningand support, medication history, andnutritional status.The "frail" older patient will likelypose the greatest challenge in choosinga palliative treatment course. Comprising10% to 25% of people overage 65, frail patients are described ashaving one or more of the followingcharacteristics: age over 85, seriouscomorbid medical conditions, dependencein activities of daily living, andat least one of the common geriatricsyndromes (delirium, dementia, urinaryor fecal incontinence, failure tothrive, a history of an osteoporoticfracture, or social neglect or abuse).[4]To date, there is no standard definitionof "frailty" that can be used foranticipating and preventing adversetreatment-related outcomes.For the individual elderly patient,the clinician should have a thorough discussion regarding the benefits andtoxicities of the proposed regimen, aswell as which, if any, second-linechemotherapy agents would be pursuedupon progression of disease.There is no evidence of improved survivalor quality of life associated withsecond- or third-line chemotherapy foradvanced NSCLC in this patientpopulation.For patients with impaired performancestatus, a phase III trial of erlotinib(Tarceva) as second-line therapyfor patients with non-small-cell lungcancer revealed an improved mediansurvival among ECOG PS 2 patientsreceiving erlotinib compared with placebo(4.3 vs 3.3 months).[5] Comparatively,PS 3 patients who receivederlotinib fared worse than those whoreceived a placebo (median survival:1.9 vs 3.1 months).Conclusions
With 60% of all cancers occurringamong individuals over age 65, andwith the percentage of people over 65surpassing 20% by 2003, future cooperativetrials should place greateremphasis on elderly cancer patients.Non-small-cell lung cancer patients,with their inherent predisposition towardpulmonary and cardiovascularcomorbidities, can be particularlyvulnerable to the side effects of bothdoublet and singlet chemotherapyregimens.When caring for the elderly patientwith NSCLC, open-ended communicationis essential. Compared with theiryounger counterparts, elderly patientsoften maintain different attitudes regardingillness, death, and dying.

Disclosures:

The authors have nosignificant financial interest or other relationshipwith the manufacturers of any products orproviders of any service mentioned in thisarticle.

References:

1.

The Elderly Lung Cancer Vinorelbine ItalianStudy Group: Effect of vinorelbine on qualityof life and survival of elderly patients withadvanced non-small cell lung cancer. J NatlCancer Inst 91:66-72, 1999.

2.

Schild SE, Stella PJ, Geyer SM, et al: Theoutcome of combined-modality therapy forstage III non-small cell lung cancer in the elderly.J Clin Oncol 21:3201-3206, 2003.

3.

Repetto L, Comandini D: Cancer in theelderly: Assessing patients for fitness. Crit RevOncol Hematol 35:155-160, 2000.

4.

Balducci L, Stanta G: Cancer in the frailpatient: A coming epidemic. Hematol OncolClin North Am 14:235-250, 2000.

5.

Shepherd FA, Pereira J, Ciuleanu TE, etal: A randomized placebo-controlled trial oferlotinib in patients with advanced non-smalllung cancer (NSCLC) following failure of 1stline or 2nd line chemotherapy. A National CancerInstitute of Canada Clinical Trials Group(NCIC CTG) trial (abstract 7022). Proceedingsand abstracts of the 2004 Annual Meeting ofthe American Society of Clinical OncologyAvailable at www.asco.org. Accessed 8/3/04.