- Email: [email protected]
P-559 A phase II study of oxallplatln and docetaxel In patients with advanced non-small-cell lung cancer (NSCLC)
Posters/Non-small cell lung c a n c e r - Advanced disease Oll~l~O control and survival Howe~r. we snduld be coutlous that the Inci0enoe of severe side of/acts like Interstitial lung disease may also be Iqlglner
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II~ucl]foi'em'ellplatlnend docetexel In Icatlents
Ichmnced non.-smdl-~l lung CI'lCIr CNSCLC) L. Raez. E S~tos, C. Rochaq_lma, E Roman, P Kumar, N Farfan, T Deoesare, G Lopes, M Rasado, J Wu Ltnh.emJtyorM~rnJ. M~mJ. F/o r~o'a. USA
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Figure 1 Overall SL.rVlval results for patients with non-small cell lung cancer (NSCLC) treate0 ~ h gefitlnlb s t r a ~ 0 ac~rOlng to s m ~ n g status
•
C~Ir~c~ IIc~orI that ~fluIn¢I thI hIzIr~ of dIIdh In i a n c a d no~-amall call lung canesr ~5CLC) pltklnli ~ri~ad with pki~num-biiid c~irnothirip~: A n i ~ f i I i of Indh~duil p~kiM i r a from p r o I p I d ~ tdali In mono¢int~c aeffing
O. R a b o s ~ o ,
I ~zlc, S ~llo, O ~ 1 ~
Z Tomato
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Backgrouml: Tn~ 10~ntlflcatlon of I m p l a n t pr~re=me~ and tre~me~ fa=ors Influen=ng su~Wal In Int~Mdual p=lents u n ~ g o l ~ ~ o t h e r ~ y for a~n~ NCSLC remains the ~ a l ~ We a n a ~ two ~ l y ac~ept~ parameters (extent of dls~as~ arx:l performance status) together wfth response to therapy and patient age and gender trying to q u a r t ~ their Influence on hazar0 of beath M ~ h o ¢ l r IndM~ual patient data from four phase II,qll S~LJOleScon~u¢~ed a¢ the InstItLJ~e for Oncology and Radology of Serl::Wa from 1990 to 2004, were rm/l~ved to per/ors muItlva'late Cox regression analysis Survival times were adjusted (by 3 months) according to landmark method Patients were troat~ with cispiatln {'120me'm=) or carooplatln (400mg,irr~ and thereafter AWC 5}base0 0oul::Wets ortrlpl~s (seconD-generation regimens) Cycies were repeated every 4 weeks, response to therapy was evaluated acoordlng to WHO criteria RIIMIRIE 362 patler~s were Inoluded Into analysis M,"F ratio was 31B/44, older trlan 65 wgrg 59 0L.( 0f362 patients, stage IIIhAV Iqad 165/197 patients, Initial PS 0111723 w-as recorded In 31..'1871113/31 patients respectively; modan of ro~elved cycles was 4. Complete response {CR) was recorbed In g patients, pa~lal response ( ~ ) I n 108 p a t ~ t s (response rate ~ ) I n '117 ~tlents, 32%) stable disease {SO)In 167 patients (46%) and progressive dlseeso {PO)In 79 p a i n t s (22%). Median survival time was 7 months. Final Cox PH model for hazard of death contalmd response to therapy, stage and PS There was no ~ 1 ~ n c e that adding addItional cevarlatos as gender (LRtest, p = 0 4B~) or age a0ove 65 (LR text, p = 0.371) Improved the fit of the Cox proportional Iqazards moOgl alrga0y containing stage, response to trgatmer~t and PS variables Stage IV of the disease was associated with 31% higher rlsk of death at any g ~ n ~me ~ R = 1.31 [1.02-1.61 ]). 'Wqlle SO as the ~ t response to therapy did not ~ a r statistically s l ~ c a n t Increase In ~ a ~ of ~ t h comperer~ to ( C R Y ) : HR = 1 ~ , p = 0 '150, hazard r~lo for a ~ p ~ n t s r e l ~ to the p a i n t s was estlm~ed to ~ 2.03 [1 .~-2.63]. As e ~ = e d ~ ' 1 did n= c a ~ higher Hsk of ~ a t h then ~ 0 (HR='1 31, p = 0 17), ~ l e HRs for ~ 2 and ~ 3 pts were slgn~ca'qt~ h l ~ r and similar In m a g n I t ~ ('1 93 ['1 ~ - 2 94] and 2 02 [1 11-3 ~ ] r~spe~lvely) C.on¢:luiIon: Favorable response to treatment ~3;,) as well as good PS (0) and stage IIIB has the lowest Msk of dealh at anytime, compared ~th other categories of patients recoMng ct~emotherapy. Seems that patlenCs with SO as the Isest response do not hava higher hazard of death then RR enos vwllc~ further question the Impedance of achieving RR In advanoed NSCLC
Bad¢ground: Clsplatln (DDP) has Icaen for a long time the "classic" agent for the treatment of NSCLC Despite Its beftertoxicity profile, carboplatln has unable to totally replace DDP Controversy still exists b o ~ tlqGs8 agents regarcing similar etflcacy Oxallplatln represents an alternative to be conslberecl_ Cosigning oxallplatln and docata~gl (DOCOX I Is a 01ologlcally rational and feasible option Oxallpiatln crossqlr~s DNA s~rands and Iqas shown more ac~lvlty In vltro man ODP Oocata~el Is a mltotlo spindle Inlqlbltor, approved as flrst41ne therapy for metastatic (or am,'anmd) non-small cell lung cancer (NSCLC) M d h e s l r We beslgned a plqase II thai to evaluate the elTIcacy and safe#/ of OOCOX In flrst41no Voatment of patients (pts) wltn stage IIIB/]V NSCLC and ECOG performance status (PSI 0-1 We ha,we to date enrolled ;'5 I~S out of 30 Initially plannecL Treatmet~ IncludecL doogCax~ 70 mg,rm2 followed c0(allplatln 130 mg,trr?" on clay 1, and pegtllgastrlm 6 mg sul:x:utaneous on =:lay 2, for a maximum of six cycles I/there w-as ovI0enco of respense Roaulti: Median age Is 59 ,~ars (range 35-70), '14 of the patients are female, 19 are White, ahe 14 are Hlspam'qlc Twenty subjects had an ECOG F~ 1 The most common h l s t o l ~ Is ~ n c o a r ~ n o m a In 20 ~s ( 8 ~ ) , and most of them am stage IV 23/25 (92%) Brain metastases were present In B of the 25 I~S (32%), and they recel.,ed palliative radiation therapy prlorto enrollment Data for response Is avalla01e In 1 g I:XS A partial response wax seen In 7 pts (37%, 90% CI 19-5B%), and stable disease In B (42%, 90% CI 23-63%) Four pts 121%, 90% CI 8-42% 1 had disease progression Four addtlonal i~s could not Ise assessed for response hL.( are being followed for survlval Eightyelgll cycles of tlqls com~natlon chemotherapy Iqave ~ a~"nlnlstergd ano v e have doournentod four severe adverse e,,ents {SAE) that mlgl't be related to this com01natlon d i a n a (G3) In one pt {doceta,~e~oxallplatln), hypersensitlvlty (G3) In a n o t ~ one (desgta~)l), and 011=oral lover e ~ r g m ~ ebema (G3) In two pts {clocetaxe~) Otherunr~ated grabe 3 toxicity reportedlnciuded Dyspnea No grade 3 or 4 neutropenla have ~ noted Conclmmlon: The OOCOX combination Is safe and ef1'lcacious In thetreatment of NSCLC 0Gspito the had prognostic factors (large number of stage IV pts and several with hraln metastaslsl of tlqls cohort Final results wlll Ica preset]ted In the maetlng A mndomlzad ~ to d o ~ l
I I~lu~ ~ p~InI~ told docatmml compamcl
m o n o t t l m p y In p ~ l a n l i w l ~ p r w l o u i l y |m~led
Ichm nced N'::CLC D, Ra~quna~narao ~. P Kore~sk?-. P Sen,,ratowskJ], A Gruszfedd4, K Lakslqmalah ~, A Szc~esna s, M Savln7, K_ Yen =, A Blqatnagar~, M G~eenTM tN'aram's lns~ ofMecl ScJ. P~nJagutta Hyclamb~cl. lnc~a.
~Sz~X~ S~c~a~tyczny ~ fa/oyg~ra. K r ~ w . P~n~1. 3Sz,o~ta~ Spac~a~s~czny rn A#Ta~a, Szcz_ac~n. Poland. '* Warrn~nsXo4vf~_urst~ Cantmm c~o~J, omz~, ~ n ~ , oP0¢WaJ M~nor~t fnst 01 ~co~og~Z Cat, car Car~ar Rf M ~ I ~ I CX~. Daflas. USA, e 7gtan Pharmacaut~c~ts. tnc. South San Fm~cJsc~. USA, fo,Mec/ U~Jv olSouth C a r o ~ . Char~s~on. USA Background: Plvanex (plvalpylc~rmetl'~l bL.ityratel, a hlstone deacetylase Inhibitor, Induce= tumor dlft, ren¢latlon arx:Vor apoptosls. Previous studes 0emonstrated Plvane~ was we~l toleraCed as a single agent and In combination with dooe~ax:~, a ~ suggested antltumor a~vlty In NSCLC. In v11ro studes demonstrated syner£1stlc antlcanoer ac~lvlty wilh Oooe~ax~ This multlcenter trlal was 0eslgnecl to O~rTnlne If Rvar~o¢ an0 0oo~a.~l Improved survlval ovar docatax:e~ mo~tl"Kxaw M ~ h e s l r Patients wlth NSCLC wtlo progressed after a platlnurn-contalnlrx 3 ct]emothera~ regmen were ran0omlze0 to PIvarox 2 5 g/sclM clays 1-3 and doogCa.~l 75 mg/sqM day 4 (Arm A), or docata.~l 75 mg/sqM alone on clay 1 {Arm B I Cycles were repeated every 2'1 days until progression ~eaMIhE 22B pts wltlq ECOG 0-2 were randorn~e~ Treatmetl arms (A vs B) were similar In age (60 5 vs 59 0 yTS), gender (68 7% male vs 71 9%), performance status {B4 2% ECOG 1 or 2 vs B2.5%), Icest response to prior platinum chemotherapy (30 1% PR/CR vs 27 2%) and prior taxano therapy (3B 6% vs 37 7%1. Marian nurn bars of treatment cycles were 3 for Arm A and 3 for Arm B. Median survival of 4.6 m o (95%CI. 3.4-5.B) for AFro A was lower than the fi 4 me (95%0 5 0-B 4)forArrn B Medlantlme to tumor progression was similar (2 3 me vs 2 8 me ). Corflrmed tumor responses were seen In 2 ('1 B%) patients In Arm A and 12 (10 6%) patients In Arm [] Most common Gra0e 3 or 4 AEs were (Arm A vs. B) neutropenla (35% vs 35%), leukopenla ('17% vs '12%), oyspnoea (15% vs 8%), anaemia (10% vs 4%), asthenla (7% vs 4%), pneurnonla (6% vs 5%). febrile neLXropenla (5% vs 5%), c o u ~ (4% vs 0%), respirat~,/' failure (4% vs 0%), a~omlnal pain (4% vs I%), der~'dratlon {4% vs 4%), and pleural effusion (4% vs 2°/=I Conclu=l~nK: Tne combination of Plvar~x and 0oceta:
[~A
pl~
$265
II~ucl]foi'em'ellplatlnend docetexel In Icatlents
Ichmnced non.-smdl-~l lung CI'lCIr CNSCLC) L. Raez. E S~tos, C. Rochaq_lma, E Roman, P Kumar, N Farfan, T Deoesare, G Lopes, M Rasado, J Wu Ltnh.emJtyorM~rnJ. M~mJ. F/o r~o'a. USA
I. i i
,.I-
II
t,
a
I
II
Figure 1 Overall SL.rVlval results for patients with non-small cell lung cancer (NSCLC) treate0 ~ h gefitlnlb s t r a ~ 0 ac~rOlng to s m ~ n g status
•
C~Ir~c~ IIc~orI that ~fluIn¢I thI hIzIr~ of dIIdh In i a n c a d no~-amall call lung canesr ~5CLC) pltklnli ~ri~ad with pki~num-biiid c~irnothirip~: A n i ~ f i I i of Indh~duil p~kiM i r a from p r o I p I d ~ tdali In mono¢int~c aeffing
O. R a b o s ~ o ,
I ~zlc, S ~llo, O ~ 1 ~
Z Tomato
Sns#t~g
Backgrouml: Tn~ 10~ntlflcatlon of I m p l a n t pr~re=me~ and tre~me~ fa=ors Influen=ng su~Wal In Int~Mdual p=lents u n ~ g o l ~ ~ o t h e r ~ y for a~n~ NCSLC remains the ~ a l ~ We a n a ~ two ~ l y ac~ept~ parameters (extent of dls~as~ arx:l performance status) together wfth response to therapy and patient age and gender trying to q u a r t ~ their Influence on hazar0 of beath M ~ h o ¢ l r IndM~ual patient data from four phase II,qll S~LJOleScon~u¢~ed a¢ the InstItLJ~e for Oncology and Radology of Serl::Wa from 1990 to 2004, were rm/l~ved to per/ors muItlva'late Cox regression analysis Survival times were adjusted (by 3 months) according to landmark method Patients were troat~ with cispiatln {'120me'm=) or carooplatln (400mg,irr~ and thereafter AWC 5}base0 0oul::Wets ortrlpl~s (seconD-generation regimens) Cycies were repeated every 4 weeks, response to therapy was evaluated acoordlng to WHO criteria RIIMIRIE 362 patler~s were Inoluded Into analysis M,"F ratio was 31B/44, older trlan 65 wgrg 59 0L.( 0f362 patients, stage IIIhAV Iqad 165/197 patients, Initial PS 0111723 w-as recorded In 31..'1871113/31 patients respectively; modan of ro~elved cycles was 4. Complete response {CR) was recorbed In g patients, pa~lal response ( ~ ) I n 108 p a t ~ t s (response rate ~ ) I n '117 ~tlents, 32%) stable disease {SO)In 167 patients (46%) and progressive dlseeso {PO)In 79 p a i n t s (22%). Median survival time was 7 months. Final Cox PH model for hazard of death contalmd response to therapy, stage and PS There was no ~ 1 ~ n c e that adding addItional cevarlatos as gender (LRtest, p = 0 4B~) or age a0ove 65 (LR text, p = 0.371) Improved the fit of the Cox proportional Iqazards moOgl alrga0y containing stage, response to trgatmer~t and PS variables Stage IV of the disease was associated with 31% higher rlsk of death at any g ~ n ~me ~ R = 1.31 [1.02-1.61 ]). 'Wqlle SO as the ~ t response to therapy did not ~ a r statistically s l ~ c a n t Increase In ~ a ~ of ~ t h comperer~ to ( C R Y ) : HR = 1 ~ , p = 0 '150, hazard r~lo for a ~ p ~ n t s r e l ~ to the p a i n t s was estlm~ed to ~ 2.03 [1 .~-2.63]. As e ~ = e d ~ ' 1 did n= c a ~ higher Hsk of ~ a t h then ~ 0 (HR='1 31, p = 0 17), ~ l e HRs for ~ 2 and ~ 3 pts were slgn~ca'qt~ h l ~ r and similar In m a g n I t ~ ('1 93 ['1 ~ - 2 94] and 2 02 [1 11-3 ~ ] r~spe~lvely) C.on¢:luiIon: Favorable response to treatment ~3;,) as well as good PS (0) and stage IIIB has the lowest Msk of dealh at anytime, compared ~th other categories of patients recoMng ct~emotherapy. Seems that patlenCs with SO as the Isest response do not hava higher hazard of death then RR enos vwllc~ further question the Impedance of achieving RR In advanoed NSCLC
Bad¢ground: Clsplatln (DDP) has Icaen for a long time the "classic" agent for the treatment of NSCLC Despite Its beftertoxicity profile, carboplatln has unable to totally replace DDP Controversy still exists b o ~ tlqGs8 agents regarcing similar etflcacy Oxallplatln represents an alternative to be conslberecl_ Cosigning oxallplatln and docata~gl (DOCOX I Is a 01ologlcally rational and feasible option Oxallpiatln crossqlr~s DNA s~rands and Iqas shown more ac~lvlty In vltro man ODP Oocata~el Is a mltotlo spindle Inlqlbltor, approved as flrst41ne therapy for metastatic (or am,'anmd) non-small cell lung cancer (NSCLC) M d h e s l r We beslgned a plqase II thai to evaluate the elTIcacy and safe#/ of OOCOX In flrst41no Voatment of patients (pts) wltn stage IIIB/]V NSCLC and ECOG performance status (PSI 0-1 We ha,we to date enrolled ;'5 I~S out of 30 Initially plannecL Treatmet~ IncludecL doogCax~ 70 mg,rm2 followed c0(allplatln 130 mg,trr?" on clay 1, and pegtllgastrlm 6 mg sul:x:utaneous on =:lay 2, for a maximum of six cycles I/there w-as ovI0enco of respense Roaulti: Median age Is 59 ,~ars (range 35-70), '14 of the patients are female, 19 are White, ahe 14 are Hlspam'qlc Twenty subjects had an ECOG F~ 1 The most common h l s t o l ~ Is ~ n c o a r ~ n o m a In 20 ~s ( 8 ~ ) , and most of them am stage IV 23/25 (92%) Brain metastases were present In B of the 25 I~S (32%), and they recel.,ed palliative radiation therapy prlorto enrollment Data for response Is avalla01e In 1 g I:XS A partial response wax seen In 7 pts (37%, 90% CI 19-5B%), and stable disease In B (42%, 90% CI 23-63%) Four pts 121%, 90% CI 8-42% 1 had disease progression Four addtlonal i~s could not Ise assessed for response hL.( are being followed for survlval Eightyelgll cycles of tlqls com~natlon chemotherapy Iqave ~ a~"nlnlstergd ano v e have doournentod four severe adverse e,,ents {SAE) that mlgl't be related to this com01natlon d i a n a (G3) In one pt {doceta,~e~oxallplatln), hypersensitlvlty (G3) In a n o t ~ one (desgta~)l), and 011=oral lover e ~ r g m ~ ebema (G3) In two pts {clocetaxe~) Otherunr~ated grabe 3 toxicity reportedlnciuded Dyspnea No grade 3 or 4 neutropenla have ~ noted Conclmmlon: The OOCOX combination Is safe and ef1'lcacious In thetreatment of NSCLC 0Gspito the had prognostic factors (large number of stage IV pts and several with hraln metastaslsl of tlqls cohort Final results wlll Ica preset]ted In the maetlng A mndomlzad ~ to d o ~ l
I I~lu~ ~ p~InI~ told docatmml compamcl
m o n o t t l m p y In p ~ l a n l i w l ~ p r w l o u i l y |m~led
Ichm nced N'::CLC D, Ra~quna~narao ~. P Kore~sk?-. P Sen,,ratowskJ], A Gruszfedd4, K Lakslqmalah ~, A Szc~esna s, M Savln7, K_ Yen =, A Blqatnagar~, M G~eenTM tN'aram's lns~ ofMecl ScJ. P~nJagutta Hyclamb~cl. lnc~a.
~Sz~X~ S~c~a~tyczny ~ fa/oyg~ra. K r ~ w . P~n~1. 3Sz,o~ta~ Spac~a~s~czny rn A#Ta~a, Szcz_ac~n. Poland. '* Warrn~nsXo4vf~_urst~ Cantmm c~o~J, omz~, ~ n ~ , oP0¢WaJ M~nor~t fnst 01 ~co~og~Z Cat, car Car~ar Rf M ~ I ~ I CX~. Daflas. USA, e 7gtan Pharmacaut~c~ts. tnc. South San Fm~cJsc~. USA, fo,Mec/ U~Jv olSouth C a r o ~ . Char~s~on. USA Background: Plvanex (plvalpylc~rmetl'~l bL.ityratel, a hlstone deacetylase Inhibitor, Induce= tumor dlft, ren¢latlon arx:Vor apoptosls. Previous studes 0emonstrated Plvane~ was we~l toleraCed as a single agent and In combination with dooe~ax:~, a ~ suggested antltumor a~vlty In NSCLC. In v11ro studes demonstrated syner£1stlc antlcanoer ac~lvlty wilh Oooe~ax~ This multlcenter trlal was 0eslgnecl to O~rTnlne If Rvar~o¢ an0 0oo~a.~l Improved survlval ovar docatax:e~ mo~tl"Kxaw M ~ h e s l r Patients wlth NSCLC wtlo progressed after a platlnurn-contalnlrx 3 ct]emothera~ regmen were ran0omlze0 to PIvarox 2 5 g/sclM clays 1-3 and doogCa.~l 75 mg/sqM day 4 (Arm A), or docata.~l 75 mg/sqM alone on clay 1 {Arm B I Cycles were repeated every 2'1 days until progression ~eaMIhE 22B pts wltlq ECOG 0-2 were randorn~e~ Treatmetl arms (A vs B) were similar In age (60 5 vs 59 0 yTS), gender (68 7% male vs 71 9%), performance status {B4 2% ECOG 1 or 2 vs B2.5%), Icest response to prior platinum chemotherapy (30 1% PR/CR vs 27 2%) and prior taxano therapy (3B 6% vs 37 7%1. Marian nurn bars of treatment cycles were 3 for Arm A and 3 for Arm B. Median survival of 4.6 m o (95%CI. 3.4-5.B) for AFro A was lower than the fi 4 me (95%0 5 0-B 4)forArrn B Medlantlme to tumor progression was similar (2 3 me vs 2 8 me ). Corflrmed tumor responses were seen In 2 ('1 B%) patients In Arm A and 12 (10 6%) patients In Arm [] Most common Gra0e 3 or 4 AEs were (Arm A vs. B) neutropenla (35% vs 35%), leukopenla ('17% vs '12%), oyspnoea (15% vs 8%), anaemia (10% vs 4%), asthenla (7% vs 4%), pneurnonla (6% vs 5%). febrile neLXropenla (5% vs 5%), c o u ~ (4% vs 0%), respirat~,/' failure (4% vs 0%), a~omlnal pain (4% vs I%), der~'dratlon {4% vs 4%), and pleural effusion (4% vs 2°/=I Conclu=l~nK: Tne combination of Plvar~x and 0oceta: