E25. Chemotherapy in elderly patients

542

E25. Chemotherapy in elderly patients Cesare Gndelh S G l~-oscatl Hospital. Division of Medical C~ncolog.~. Avellmo. Italy Introduction: N o n small cell lung cancer INSCLC) mav be considered typical of advanced age More than 5qO,, of lung cancer patients are diagnosed over the age of 65 and about 3qO,, over the age of 7q~ More than two-thirds of patients dying of lung cancer m the U S A are over 65 years old Elderly patients tolerate chemotherapy poorly because of comorbldltv and organ failure The prevalence of these co-morbid conditions is about twice a s high as In the general population Elderly patients w i t h NSCLC. who frequently suffer ttunor-related symptoms and need some kind of palhatlve treatment, often receive untested or inadequate treatments A cut-off of 7q~ years seems to be the most appropriate to select elderly population In fact. 7q~ years of age m a v be considered as the lower boundary of senescence, because the mcldence of age-related changes starts to increase after the age of 7q~ vears Relevant data: In advanced disease a retrospective trial of 6232 elderly patients from the S E E R tumor registry showed that chemotherapy for metastatic N S C L C seems to h a ~ the same effectiveness as that seen m randomized trials with mostly younger patients [1] Therefore. all suitable patients should be given the opportunity to consider palhatlve chemotherapy for advanced N S C L C Prospective phase II trials h a ~ demonstrated statable toxicity profile and good antlttunor activity for smgle agent chemotherapy with vmorelbme, gemcltablne and taxanes Prospective data on weekly pachtaxel have been published Fldlas et al used weekly pachtaxel on 35 advanced N S C L C elderly patients reportmg a good tolerabllltv and lnterestmg results with 23°,, C)R and lq~ 3 months of median survival [2] Docetaxel has been tested as well m the elderly population Halnsworth et al reported for weekly docetaxel 18°,, C)tk a median survival of 5 months and a favourable toxicity profile [3] Gemcltabme is the most widely lm~stlgated agent m advanced N S C L C elderly patients, reported as an active, effective and ~ r v well tolerated drug in this peculiar patient population, with response rates ranging from 16°,, to 330,, and median survival of 2 9 - 3 2 weeks [4] In phase II studies, single agent vlnorelbme p r o ~ d to be welltolerated and active, with response rates of 12-39°,, [5] Vmorelblne. in a phase III randomized trial named ELVIS (Elderly L u n g Cancer Vlnorelbme Italian Study). compared to best supportive care. has proven to improve survival and quahty of life of advanced N S C L C patients [6] As the ELVIS trial is a unique randomized controlled trial versus best supportive care ever performed in the treatment of

elderly patients with advanced NSCLC, its result is the most reliable evidence on the efficacy of chemotherapy m this subgroup of patients In order to l m p r o ~ results obtained w i t h monochemotherapy, the development of non clsplatlnbased combinations is an lnterestmg issue in the treatment of advanced N S C L C elderly patients In fact the posslblhty of havmg a c t l ~ and well-tolerated chemotherapy while preserving patient quahty of life is more attractive m the elderly The most studied non platln-based regimen is the combination of gemcltablne plus vmorelblne, proven to be active and well-tolerated m several phase II trials [4] H o w e ~ r , a large phase I l l randomized trial II~flLES Multlcenter Italian L u n g cancer in the Elderly Study), enrollmg about 7q.~ patients, showed that polychemotherapy w i t h gemcltablne and vlnorelbme does not l m p r o ~ any outcome Iresponse rate, time to progression, survival or quahty of life) as compared to smgle agent chemotherapy w i t h vmorelblne or gemcltabme [7] In clmlcal practice, smgle agent chemotherapy should r e m a m the standard treatment Feaslblhtv of clsplatln-based polychemotherapy remams an open issue and has been recently addressed bv some retrospective analvses of randomized trials without age limits, suggestmg that advanced age alone should not preclude a g g r e s s l ~ clsplatm-based treatment to fit N S C L C elderly patients [8] The e~adence from these analvses could however suffer from selection bias. because their target population m a v not be representative of the whole elderly population but only of a small subgroup thought to be eligible for aggressive treatments bv mvestlgators [9] Prospective clmlcal trials w i t h inclusion criteria selective for elderly population are to be considered the unique tool for investigating clsplatln-based chemotherapy in this cllrncal settmg More recently some prospective phase II trials h a ~ explored innovative schedules ofclsplatm dehvery that could be more suitable to elderly population [lq~] Conclusion: Although the number of elderly patients is increasing, requlrmg specific attitudes and treatments, few controlled clmlcal trials of N S C L C chemotherapy in the elderly have been performed However, clinical research is now focusmg on this issue, and we expect in the near future some specifically designed clmlcal trials The two m a i n research lines to explore in the near future are the mtroductlon of biological agents in the treatment schemes and the development of specifically designed schedules of clsplatln-based regimens A m o n g new biologic agents, the Epidermal Growth Factor Receptor tvroslne-

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a favourable toxicity profile, potentially suitable to elderly population, is being investigated Howexer, to plan medical treatment m NSCLC elderly patients, and to further mdlvlduahze treatment choice, it is mandatory to practice a comprehensive geriatric assessment (CGA) including assessment of comorbldlty, SOClOeconomic conditions, functional dependence, emotional and cognitive conditions, an estimate of life expectancy and recognition of frailty

References [1] E a r l e ,-,-. T~'~a J & , 3 e l t , ~ RE,. Wem~'tem M,-. N e t m t a n n PJ. Weel~.~" J,- Et}e, trcene aa ,4 , h e m , , t h _ ~ p ; ¢ },,r ~t-¢an, e,t l u n ~ , an, er m t h e el, t_~l:¢ m ~ t m t e n t ~ l v a r ~ t , l e a n d pr,,pen~'~q¢ an~l:ea~- J , - h n ,-,n, ,,1 2 , , , 1 . 1 ~ 1,,~,4-1,,7,, [1] F l , t ~ P. ~?uplo, J'3. M a r t m c K et "d A p h ~ ' e II ~'tu, t:¢ ,,t weel~.l:¢ p ~ llta:.el m e l , terl;¢ pHlent~" w i t h ~t-¢an, e,t n,,n m , ~ l l , e l l l u n g , an, _~ , - l m ,- an, _~ R e c 2,,,,1.7 3 ~ 4 2 - 3 ~ 4 ~ [3] H~an~,,,rth J E , Durr~ a H A . L~t,t-r! & et ~1 Weekl;¢ ,t,,, eta:.el m t h e t r e H m e n t , , t e l , t_~l;¢ pH~ent a w~th ~tvan, e,t n, ,n r e t e l l , e l l l u n ~ , ar, m , , m ~ A M m m e Pearl ,-an, _~ R e a e a r , h Netw,,rk P h ~ e II T n ~ l ,-an, _~ 2,,,,,,,8'~ 3 2 8 - 2 3 3 [4] , 3 r M e l h ,-. ,-~,,lar~ ~?. ,3~11,, ,-. et ~1 MILE~? Inve~mmt,,r~" A , trelt:/and t, ,7.~, ~ ¢ , ,t gem, ~t~c,~ne a n d ~em, lt~c,~ne + -¢~n, ,rell:,~ne ~n ~,tvan, e,t n, ,n

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243

c m ~ l l , e l l l u n g , an, ~ el, terlv p~:ent." ~ p l ~ . ' e II , t ~ tr,,m Mult:, e n t ~ I t ~ h m L t m ~ ,: m, _~ m t h e EI, t_~I:¢ 5tu, t:¢ , M I L E 6 , r m , t , , n n : e , t trl~l L u n ~ ,: an, _~ 2, ,,1.31 2 7 7 - 2 8 4 ,Trrl,telll ,:. P_~>,ne F. ,3~11,, ,:. et ~1 \ q n , ¢ e l b m e 1a w e l l t,,l_~He, t a n d • t r e e i n t h e t r e H m e n t ,,t el,t_~l,¢ p H l e n t z w i t h ~,tvan, e,t n,,n cm~lll , e l l l u n ~ , an, _~ A tw, , - ~ e p h ~ e II ~'1q_1,t:¢ E u r J ,: an, _~

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T h e EI, t_~I:¢ L u n ~ , an, _~ V m , ,rell:,me I t ~ h a n ~?tu, t:¢ ~ , ,up Erie, t~" , ,t v m , , r e l b m e ,,n q u a l i t y ,,t l l t e a n d ~'t~Vl-¢~l ,,t el,t_~l:¢ p H l e n t a w i t h • tvan, e,t n,,n cm~ll , e l l l u n g , an, er J N H 1 ,:an, er I n a 1 ~ . ~ 1

,Trrl,telll ,:. P_~r,,ne F. ,:l~,,larl & et ~1 T h e M I L E 5 ,Multi, e n t ~ Italian L u n ~ ,: an, _~ m t h e EI,t_~I:¢ 5tu, t:¢, p h ~ e 3 trl~l ~em, l t ~ o m e + v m , , r e l b l n e -ca v m , , r e l b m e a n d -ca ~em, l t ~ o l n e i n el,t_~l,¢ ~,t-¢an, e,t N S , : L,: p H l e n t a J N H 1 ,: an, ~ I n a ~5 3~,Z-37Z IS] M ~ t r , , n ~ l ,:. F e l l u J. M a r r m , 3 , er ~1 P h ~ e II trl~l ,,t 1,,w-,t,,ae, l ~ l H m a n d ~em, l t ~ o l n e i n el, t_~l,¢ p H l e n t a w i t h ~,tvan, e,t n , , n - c m ~ l l , e l l l u n ~ , an, _~ Pr, ,, A n , 8, ,, , - l m ,l,n,, ,1 2,, ~Z,2'1 ZZ 11:, ["] Lan~er ,:J. M a n , , l ~ J. ~_~n~r,t,, P. et ~1 , : l ~ l H m - b ~ a e , t ther~p:¢ t,,r el, t_~ly pHlent~" w i t h ~tVan, e,t n , , n - m t ~11-, e l l l u n g , an, _~ 1111p11,Hl,,n~" ,,t E ~ ' t ~ n ,-,,,,p~ H i v e ,-~n, ,,1,,g;e,3r,,up 5 5 ~ ~r an, t,,ml.ze, ttrl~l J N H 1 ,-an, _~ Inct fi,,,fi.~4 1 7 3 - 8 1 [1,,] P_~r,,ne F. ,3~11,, ,-. , 3 r M e l h ,- R e , - ~ l H m - b ~ a e , t ther~p;¢ },,r el,t_~l;¢ p r i m e r a w~th ~,tvan, e,t n , , n - m , ~ l l , e l l l u n ~ , an, _~ m,ph, H~,,n a ,,t E ~ : t ~ n ,-,,, ,p_~Hrce ,-~n,, ,1, ,g;¢ ,3> ,up 55"fi. ~ rand, ,m,=e,t t n ~ l l N H 1 ,:an, ~ Inct fi,,,,fi,~4l,,fi~-l,,31