natgillin/translations-raw huggingface dataset:
Et randomiseret, åbent, fase 3- multicenterstudie af ALIMTA plus cisplatin mod gemcitabin plus cisplatin med patienter, der ikke tidligere har fået kemoterapi, med lokalt fremskreden eller metastatisk (fase IIIb eller IV) ikke- småcellet lungecancer (NSCLC) viste, at ALIMTA plus cisplatin (Intent- To - Treat [ITT] population n=865) mødte dets primære endpoint og viste lignende klinisk virkning som gemcitabin plus cisplatin (ITT n=863) på samlet overlevelse (justeret hazard ratio 0, 94; 95% CI 0, 84 - 1, 05).
14 A multicentre, randomised, open-label, Phase 3 study of ALIMTA plus cisplatin versus gemcitabine plus cisplatin in chemonaive patients with locally advanced or metastatic (Stage IIIb or IV) non-small cell lung cancer (NSCLC) showed that ALIMTA plus cisplatin (Intent-To-Treat [ITT] population n = 862) met its primary endpoint and showed similar clinical efficacy as gemcitabine plus cisplatin (ITT n = 863) in overall survival (adjusted hazard ratio 0.94; 95% CI 0.84-1.05).
Alle patienter, der var inkluderet i dette studie havde en funktionsstatus for ECOG på 0 eller 1.
All patients included in this study had an ECOG performance status 0 or 1.
De primære effektanalyser var baseret på ITT- populationen.
The primary efficacy analysis was based on the ITT population.
Følsomhedsanalyser af hovedvirkningens endpoints blev også bedømt ud fra den protokolkvalificerede (PQ) population.
Sensitivity analyses of main efficacy endpoints were also assessed on the Protocol Qualified (PQ) population.
Effektalyser med brug af PQ- populationen er konsistente med analyser for ITT- populationen og understøtter non - inferiøriteten af AC mod GC.
The efficacy analyses using PQ population are consistent with the analyses for the ITT population and support the non-inferiority of AC versus GC.
Middel PFS var 4, 8 måneder for ALIMTA plus cisplatin mod 5, 1 måneder for gemcitabin plus cisplatin (justeret hazard ratio 1. 04; 95% CI 0, 94- 1, 15) og det totale respons var 30, 6% (95% CI 27, 3 - 33, 9) for Alimta plus cisplatin mod 28, 2% (95% CI 25, 0- 31, 4) for gemcitabin plus cisplatin.
Progression free survival (PFS) and overall response rate were similar between treatment arms: median PFS was 4.8 months for ALIMTA plus cisplatin versus 5.1 months for gemcitabine plus cisplatin (adjusted hazard ratio 1.04; 95% CI 0.94-1.15), and overall response rate was 30.6% (95% CI 27.3- 33.9) for ALIMTA plus cisplatin versus 28.2% (95% CI 25.0-31.4) for gemcitabine plus cisplatin.
PFS data blev delvist bekræftet af en uafhængig undersøgelse (400/ 1715 patienter blev randomiseret og udvalgt til undersøgelsen).
PFS data were partially confirmed by an independent review (400/ 1725 patients were randomly selected for review).
Analysen af indvirkningen på NSCLC- histologien for samlet overlevelse viste klinisk relevante forskelle i overlevelse baseret på histologi, se nedenstående tabel.
The analysis of the impact of NSCLC histology on overall survival demonstrated clinically relevant differences in survival according to histology, see table below.
14 Effekt af ALIMTA + cisplatin mod gemcitabin + cisplatin i førstevalgsbehandling af ikke - småcellet lungecancer – ITTpopulation og histologiske undergrupper.
ITT Population
Middel totaloverlevelse i månederJusteret ITT population og histologiske
Median Overall Survival in Months
Superiority
Hazard Ratio Superiority (HR) p-value
p- værdi
Subgroups
ALIMTA + Cisplatin
ALIMTA + Cisplatin
Gemcitabine + Cisplatin
Gemcitabine + Cisplatin
ITT population
ITT Population
10. 3 N=862
10.3 N=862
10. 3 N=863
10.3 N=863
0. 94a
0.94
0. 259
0.259
(9. 8 – 11. 2)
(9.8 – 11.2)
(9. 6 – 10. 9)
(9.6 – 10.9)
(0. 84 – 1. 05)
(0.84 – 1.05)
Adenocarcinom
Adenocarcinoma
12. 6
12.6
10. 9
10.9
0. 033
0.033
(10. 7 – 13. 6)
(10.7 – 13.6)
(10. 2
(10.2
– 11. 9)
– 11.9)
(0. 71– 0. 99)
(0.71– 0.99)
Store celler
Large Cell
10. 4
10.4
0. 67
0.67
0. 027
0.027
(8. 6
(8.6
– 14. 1)
– 14.1)
(5. 5 – 9. 0)
(5.5 – 9.0)
(0. 48– 0. 96)
(0.48– 0.96)
0. 586
0.586
(6. 8
(6.8
– 10. 2)
– 10.2)
(8. 1 – 10. 6)
(8.1 – 10.6)
(0. 81– 1. 45)
(0.81– 1.45)
Pladeepitelceller (N=473)
Squamous Cell (N=473)
(8. 4
(8.4
9. 4 – 10. 2)
9.4 – 10.2)
10. 8 (9. 5 – 12. 1)
10.8 (9.5 – 12.1)
1. 23 (1. 00– 1. 51)
1.23 (1.00– 1.51)
CI = konfidensinterval; ITT = intent- to- treat; N = samlet populationsstørrelse. a Statistisk signifikans for non- inferiøriteten med hele konfidensintervallet for HR pænt under 1. 17645 for non- inferiøriteten, margin (p <. 001).
CI = confidence interval; ITT = intent-to-treat; N = total population size. a Statistically significant for noninferiority, with the entire confidence interval for HR well below the 1.17645 noninferiority margin (p < 0.001).
Kaplan Meier kurver over total overlevelse efter histologi
15 Kaplan Meier Plots of Overall Survival by Histology
Patienter, der blev behandlet med ALIMTA og cisplatin havde brug for færre transfusioner (16, 4% mod 28, 9%, p < 0, 001), transfusioner af røde blodlegemer (16, 1% mod 27, 3%, p < 0, 001) og blodpladetransfusioner (1, 8% mod 4, 2%, p=0, 002).
Patients treated with ALIMTA and cisplatin required fewer transfusions (16.4% versus 28.9%, p < 0.001), red blood cell transfusions (16.1% versus 27.3%, p < 0.001) and platelet transfusions (1.8% versus 4.5%, p=0.002).
Patienterne behøvede ligeledes mindre erythropoietin/ darbopoietin (10, 4% mod 18, 1%, p < 0, 001), G- CSF/ GM- CSF (3, 1% mod 6, 1%, p=0, 004) og midler med jern (4, 3 5 mod 7, 0%, p=0, 021).
Patients also required lower administration of erythropoietin/ darbopoietin (10.4% versus 18.1%, p < 0.001), G-CSF/ GM-CSF (3.1% versus 6.1%, p=0.004), and iron preparations (4.3% versus 7.0%, p=0.021).
Pemetrexeds farmakokinetiske egenskaber efter enkeltstofadministration er blevet vurderet hos 426 cancerpatienter med forskellige typer massive tumorer i doser på 0, 2- 838 mg/ m2 infunderet over 10 minutter.
The pharmacokinetic properties of pemetrexed following single-agent administration have been evaluated in 426 cancer patients with a variety of solid tumours at doses ranging from 0.2 to 838 mg/ m2 infused over a 10-minute period.
Pemetrexed har et steady state- fordelingsvolumen på 9 l/ m2.
Pemetrexed has a steady-state volume of distribution of 9 l/ m2.
In vitro- forsøg tyder på, at omtrent 81% bindes til plasmaproteiner.
In vitro studies indicate that pemetrexed is approximately 81% bound to plasma proteins.
Pemetrexeds samlede systemiske
Pemetrexed is primarily eliminated in the urine, with 70% to 90% of the administered dose being recovered unchanged in urine within the first 24 hours following administration.
15 clearance er 91, 8 ml/ min, og halveringstiden i plasma er 3, 5 timer hos patienter med normal nyre - funktion (kreatinin- clearance på 90 ml/ min).
Pemetrexed total systemic clearance is 91.8 ml/ min and the elimination half-life from plasma is 3.5 hours in patients with normal renal function (creatinine clearance of 90 ml/ min).
Der er en moderat variation i clearance blandt patienterne på 19, 3%.
Between patient variability in clearance is moderate at 19.3%.
Peroral folsyre og intramuskulært tilskud af B12- vitamin påvirker ikke pemetrexeds farmakokinetik.
Oral folic acid and intramuscular vitamin B12 supplementation do not affect the pharmacokinetics of pemetrexed.
Indgift af pemetrexed til hanmus resulterede i reproduktionstoksicitet karakteriseret ved mindskede fertilitetsrater og testikelatrofi.
Administration of pemetrexed to male mice resulted in reproductive toxicity characterised by reduced fertility rates and testicular atrophy.
Der blev set en påvirkning af testiklerne (degenerering/ nekrose af seminiferous epithelium) i et forsøg udført i beaglehunde, der fik intravenøse bolus injektioner i 9 måneder.
In a study conducted in beagle dog by intravenous bolus injection for 9 months, testicular findings (degeneration/ necrosis of the seminiferous epithelium) have been observed.
Dette tyder på, at pemetrexed kan nedsætte fertiliteten hos mænd.
This suggests that pemetrexed may impair male fertility.
Den kvindelige fertilitet blev ikke undersøgt.
Female fertility was not investigated.
Pemetrexed var hverken mutagent i in vitro- testen for kromosomafvigelse hos kinesiske hamstere eller i Ames- testen.
16 Pemetrexed was not mutagenic in either the in vitro chromosome aberration test in Chinese hamster ovary cells, or the Ames test.
Pemetrexed har vist sig at være clastogent hos mus i in vivo- mikronukleustesten.
Pemetrexed has been shown to be clastogenic in the in vivo micronucleus test in the mouse.
Der er ikke foretaget forsøg til klarlæggelse af pemetrexeds mulige karcinogene effekt.
Studies to assess the carcinogenic potential of pemetrexed have not been conducted.
Pemetrexed er fysisk inkompatibelt med fortyndinger, der indeholder calcium, heriblandt Ringers laktat og Ringers væske.
Pemetrexed is physically incompatible with diluents containing calcium, including lactated Ringer’ s Injection and Ringer’ s Injection.
Samtidig indgivelse af pemetrexed og andre lægemidler og fortyndinger er ikke blevet undersøgt og kan derfor ikke anbefales.
In the absence of compatibility studies this medicinal product must not be mixed with other medicinal products.
Rekonstituerede opløsninger og infusionsopløsninger:
Reconstituted and Infusion Solutions:
Rekonstituerede opløsninger og infusionsopløsninger af pemetrexed viste sig at have en kemisk og fysisk holdbarhed på 24 timer, når det blev nedkølet eller opbevaret ved 25 °C.
Chemical and physical in-use stability of reconstituted and infusion solutions of pemetrexed were demonstrated for 24 hours at refrigerated temperature or 25°C.
Holdbarheden vil normalt ikke være mere end 24 timer ved 2- 8 °C, medmindre rekonstituering/ fortynding er fundet sted under kontrollerede og validerede aseptiske forhold.
If not used immediately, in-use storage times and conditions prior to use are the responsibility of the user and would normally not be longer than 24 hours at 2 to 8°C, unless reconstitution / dilution has taken place in controlled and validated aseptic conditions.
Ubrudt hætteglas:
Unopened vial:
16 For opbevaringsforhold for det rekonstituerede lægemiddel, se sektion 6. 3.
For storage conditions of the reconstituted medicinal product see section 6.3.
Frysetørret pulver i hætteglas af type I.
Powder in Type I glass vial.
Pakning med 1 hætteglas.
Rubber stopper.
6. 6 Regler for destruktion og anden håndtering
17 6.6 Special precautions for disposal and other handling
Hætteglas med 100 mg rekonstitueres med 4, 2 ml natriumchloridinjektionsvæske 9 mg/ ml (0, 9%), uden konserveringsmiddel, til en opløsning indeholdende 25 mg/ ml pemetrexed.
Reconstitute 100-mg vials with 4.2 ml of sodium chloride 9 mg/ ml (0.9%) solution for injection, without preservative, resulting in a solution containing 25 mg/ ml pemetrexed.
Den rekonstituerede opløsning har en pH- værdi på 6, 6- 7, 8.
The pH of the reconstituted solution is between 6.6 and 7.8.
Den passende mængde rekonstitueret pemetrexedopløsning skal fortyndes yderligere til 100 ml med 0, 9% natriumchloridinjektionsvæske, uden konserveringsmiddel, og indgives som langsom intravenøs infusion over 10 minutter.
The appropriate volume of reconstituted pemetrexed solution should be further diluted to 100 ml with sodium chloride 9 mg/ ml (0.9%) solution for injection, without preservative, and administered as an intravenous infusion over 10 minutes.
Eli Lilly Nederland B. V., Grootslag 1- 5, NL- 3991 RA Houten, Holland.
Eli Lilly Nederland B. V., Grootslag 1-5, NL-3991 RA, Houten, The Netherlands.
20. september 2004
20 September 2004
Hvert hætteglas skal rekonstitueres med 20 ml natriumchlorid 9 mg/ ml (0, 9%) injektionsvæske, som resulterer i en opløsning på 25 mg/ ml.
Each vial must be reconstituted with 20 ml of sodium chloride 9 mg/ ml (0.9%) solution for injection resulting in 25 mg/ ml of solution.
19 ALIMTA givet alene:
19 ALIMTA as single agent:
Til patienter, der behandles for ikke- småcellet lungecancer efter tidligere behandling med kemoterapi, er den anbefalede dosis af ALIMTA 500 mg/ m2 legemsoverflade indgivet som intravenøs infusion over 10 minutter på den første dag i hver 21- dages- cyklus.
In patients treated for non-small cell lung cancer after prior chemotherapy, the recommended dose of ALIMTA is 500 mg/ m2 BSA administered as an intravenous infusion over 10 minutes on the first day of each 21-day cycle.
20 Tabel 2 – Dosisjustering for ALIMTA (som enkeltstof eller i kombination) OG cisplatin – ikke- hæmatologisk toksicitet a, b
20 Table 2 - Dose Modification Table for ALIMTA (as single agent or in combination) and Cisplatin– Non-haematologic Toxicities a, b
Dosis af ALIMTA 2 (mg/ m)
Dose of ALIMTA 2 (mg/ m)
Mucositis af grad 3 eller 4
Grade 3 or 4 mucositis a
National Cancer Institute Common Toxicity Criteria (CTC) (v2. 0; NCI 1998) b Undtagen neurotoksicitet
National Cancer Institute Common Toxicity Criteria (CTC v2.0; NCI 1998) b Excluding neurotoxicity
Tabel 3 – Dosisjustering for ALIMTA (som enkeltstof eller i kombination) OG cisplatin – neurotoksicitet
Table 3 - Dose Modification for ALIMTA (as single agent or in combination) and Cisplatin – Neurotoxicity
CTCa- grad
CTCa Grade
af ALIMTA (mg/ m2)
Dose of ALIMTA (mg/ m2)
Overfølsomhed over for det aktive stof eller over for et eller flere af hjælpestofferne.
Breast-feeding must be discontinued during pemetrexed therapy (see section 4.6).
4. 6).
21 Concomitant yellow fever vaccine (see section 4.5).
4. 5).
4.4 Special warnings and precautions for use
Som et resultat heraf frarådes samtidig indgift af levende svækkede vacciner (med undtagelse af gul feber, der er kontraindiceret) (se pkt.
As a result, concomitant use of live attenuated vaccines (except yellow fever which is contraindicated) is not recommended (see section 4.3 and 4.5).
4. 3 og 4. 5).
Pemetrexed can have genetically damaging effects.
22 Pemetrexed kan have skadelige genetiske virkninger.
22 recommended.
Det anbefales at anvende prævention eller afholde sig fra seksuelt samkvem.
Owing to the possibility of pemetrexed treatment causing irreversible infertility, men are advised to seek counselling on sperm storage before starting treatment.
23 Følgende samtidig brug frarådes:
Concomitant use not recommended:
4. 6 Graviditet og amning
23 4.6 Pregnancy and lactation
24 Organsystem - klasse
24 System Organ
25 Meget almindelige - > 10%; Almindelige ≥ 1% og < 10% (til denne tabel blev der anvendt en afskæringsværdi på 5% til inkludering af alle hændelser, hvor indberetteren anså, at bivirkningen muligvis var forbundet med pemetrexed og cisplatin).
For the purpose of this table a cut off of 5% was used for inclusion of all events where the reporter considered a possible relationship to pemetrexed and cisplatin.
De klinisk relevante CTC- toksiciteter, som blev rapporteret hos ≥ 1% og < 5% (almindelig) af de patienter, der var randomiseret til cisplatin og pemetrexed, omfattede: nyresvigt, infektion, pyreksi, febril neutropeni, forhøjet ASAT, ALAT og GGT, nældefeber og brystsmerter.
Clinically relevant CTC toxicities that were reported in ≥ 1% and < 5% (common) of the patients that were randomly assigned to receive cisplatin and pemetrexed include: renal failure, infection, pyrexia, febrile neutropenia, increased AST, ALT, and GGT, urticaria and chest pain.
Blod - og lymfesystem
Blood and Lymphatic System
Lever og galde
Hepatobilliary Disorders
14, 0 0, 0
0.0
6, 2 0, 0
0.0
6, 8 0, 4 6, 4 0, 4
0.4**
1, 8 0, 0 37, 7 2, 2
2.2**
26 De klinisk relevante CTC- toksiciteter, som blev rapporteret hos ≥ 1% og < 5% (almindelig) af de patienter, der var randomiseret til pemetrexed, omfattede: infektion uden neutropeni, febril neutropeni, allergisk reaktion/ overfølsomhed, forhøjet kreatinin, motorisk neuropati, sensorisk neuropati, erythema multiforme og mavesmerter.
26 Clinically relevant CTC toxicities that were reported in ≥ 1% and < 5% (common) of the patients that were randomly assigned to pemetrexed include: infection without neutropenia, febrile neutropenia, allergic reaction/ hypersensitivity, increased creatinine, motor neuropathy, sensory neuropathy, erythema multiforme, and abdominal pain.
Organsystem - klasse
27 System Organ Class
33, 0 * 5, 6 *
33.0* 5.6*
45, 7 * 9, 9 *
45.7* 9.9*
29, 0 * 15, 1 *
29.0* 15.1*
38, 4 * 26, 7 *
38.4* 26.7*
44, 9 4, 9
6.7
27 Organsystem - klasse
44.9
Hyppighed
4.9
Bivirkning **
Nervous System
Pemetrexed / cisplatin (N = 839)
Common
Gemcitabin / cisplatin (N = 830)
Neuropathy- sensory
Toksicitet i Toksicitet i alle grader grad 3- 4 (%) (%)
8.5*
Toksicitet i Toksicitet alle grader i grad 3- 4 (%) (%)
0.0*
6, 8
6.6
Til denne tabel blev anvendt en afskæringsværdi på 5% til inkludering af alle hændelser, hvor indberetterne vurderede, at bivirkningen muligvis var forbundet med pemetrexed og cisplatin.
For the purpose of this table, a cut-off of 5% was used for inclusion of all events where the reporter considered a possible relationship to pemetrexed and cisplatin).
Klinisk relevant toksicitet, som blev rapporteret hos ≥ 1% og ≤ 5% (almindelig) af de patienter, der var randomiseret til cisplatin og pemetrexed, omfattede: forhøjet AST, forhøjet ALT, infektion, febril neutropeni, nyresvigt, pyreksi, dehydrering, konjunktivitis og nedsat kreatinin- clearance.
AST increase, ALT increase, infection, febrile neutropenia, renal failure, pyrexia, dehydration, conjunctivitis, and creatinine clearance decrease.
4. 4).
Cases of radiation pneumonitis have been reported in patients treated with radiation either prior, during or subsequent to their pemetrexed therapy (see section 4.4) Cases of radiation recall have been reported in patients who have received radiotherapy previously (see section 4.4).
4. 4).
Cases of peripheral ischemia leading sometimes to extremity necrosis have been reported.
29 Effekt af ALIMTA sammen med cisplatin versus cisplatin alene til patienter med malignt pleura mesotheliom
Cisplatin in Malignant Pleural Mesothelioma
(10, 0- 14, 4)
(10.0 - 14.4) 0.020
(7, 8- 10, 7) (11, 4- 14, 9)
(7.8 - 10.7) (11.4 - 14.9) 0.051
(8, 4- 11, 9)
(8.4 - 11.9)
3, 9 6, 1
3.9 6.1
(4, 9- 6, 5)
(4.9 – 6.5) 0.001
(2, 8- 4, 4) (5, 3- 7, 0)
(2.8 - 4.4) (5.3 - 7.0) 0.008
(2, 8- 4, 5)
(2.8 - 4.5)
(3, 9- 4, 9)
4.5 (3.9 – 4.9) 0.001
(2, 1- 2, 9) (4, 3- 5, 6)
2.7 4.7 (2.1 - 2.9) (4.3 - 5.6) 0.001
41, 3%
41.3%
16, 7% 45, 5%
16.7% 45.5%
(12, 0- 22, 2) (37, 8- 53, 4)
(12.0 - 22.2) (37.8 - 53.4)
(13, 8- 26, 6)
(13.8 - 26.6)
Fishers eksakte p- niveau * Forkortelse:
Fisher’ s exact p-value* Abbreviation:
CI = konfidensinterval
CI = confidence interval * p-value refers to comparison between arms.
* p- værdi henviser til sammenligning mellem arme. ** I ALIMTA/ cisplatin- armen, randomiseret og behandlet (n = 225) og fuldt tilskud (n = 167)
** In the ALIMTA/ cisplatin arm, randomized and treated (N = 225) and fully supplemented (N = 167)
En analyse af virkningen på NSCLCs histologi for behandlingens virkning på samlet overlevelse var til fordel for ALIMTA versus docetaxel bortset fra cancerformer hovedsageligt bestående af pladeepitelceller (n=399; 9, 3 mod 8, 0 måneder, justeret HR= 0, 78; 95% CI= 0, 61- 1, 00, p= 0, 047) og til fordel for docetaxel for carcinom af pladeepitelceller (n= 172; 6, 2 versus 7, 4 måneder, justeret HR 1, 56; 95% CI= 1, 08- 2, 26, p= 0, 0018).
An analysis of the impact of NSCLC histology on the treatment effect on overall survival was in favour of ALIMTA versus docetaxel for other than predominantly squamous histologies (n=399, 9.3 versus 8.0 months, adjusted HR = 0.78; 95% CI =0 .61-1.00, p =0.047) and was in favour of docetaxel for squamous cell carcinoma histology (n=172, 6.2 versus 7.4 months, adjusted HR = 1.56; 95% CI =1.08-2.26, p =0.018).
30 Effekt af ALIMTA versus docetaxel mod NSCLC – ITT- population
Efficacy of ALIMTA vs docetaxel in NSCLC - ITT Population
Overlevelsestid (måneder) Median (m) 95% - CI for median HR
Survival Time (months) Median (m) 95% CI for median HR
(n = 283) 8, 3 (7, 0- 9, 4)
(n = 283) 8.3 (7.0 - 9.4)
(n = 288) 7, 9 (6, 3- 9, 2)
(n = 288) 7.9 (6.3 - 9.2)
95% - CI for HR P- værdi for non- inferioritet (HR)
95% CI for HR Non-inferiority p-value (HR)
Overlevelse uden progression (måneder) Median HR (95% - CI)
Progression free survival (months) Median
0, 97 (0, 82- 1, 16)
(n
Tid til behandlingssvigt (TTTF – måneder) Median
Time to treatment failure (TTTF – months) Median
HR (95% - CI)
HR (95% CI)
0, 84 (0, 71- 0, 997)
0.84 (.71 - .997)
Et randomiseret, åbent, fase 3- multicenterstudie af ALIMTA plus cisplatin mod gemcitabin plus cisplatin med patienter, der ikke tidligere har fået kemoterapi, med lokalt fremskreden eller metastatisk (fase IIIb eller IV) ikke- småcellet lungecancer (NSCLC) viste, at ALIMTA plus cisplatin (Intent- To- Treat [ITT] population n=865) mødte dets første endpoint og viste lignende klinisk virkning som gemcitabin plus cisplatin (ITT n=863) på samlet overlevelse (justeret hazard ratio 0, 94; 95% CI 0, 84- 1, 05).
31 A multicentre, randomised, open-label, Phase 3 study of ALIMTA plus cisplatin versus gemcitabine plus cisplatin in chemonaive patients with locally advanced or metastatic (Stage IIIb or IV) non-small cell lung cancer (NSCLC) showed that ALIMTA plus cisplatin (Intent-To-Treat [ITT] population n = 862) met its primary endpoint and showed similar clinical efficacy as gemcitabine plus cisplatin (ITT n = 863) in overall survival (adjusted hazard ratio 0.94; 95% CI 0.84-1.05).
Effektanlyser med brug af PQ- populationen er konsistente med analyser for ITT- populationen og understøtter non - inferøriteten af AC mod GC.
The efficacy analyses using PQ population are consistent with the analyses for the ITT population and support the non-inferiority of AC versus GC.
PFS data blev delvist bekræftet af en uafhængig undersøgelse (400/ 1715 patienter blev randomiseret udvalgt til undersøgelsen).
PFS data were partially confirmed by an independent review (400/ 1725 patients were randomly selected for review).
Analysen af indvirkningen på NSCLC histologien for samlet overlevelse viste klinisk relevante forskelle i overlevelse baseret på histologi, se nedenstående tabel.
The analysis of the impact of NSCLC histology on overall survival demonstrated clinically relevant differences in survival according to histology, see table below.
31 Effekt af ALIMTA + cisplatin mod gemcitabin + cisplatin i førstevalgshandling af ikke- småcellet lungecancer – ITTpopulation og histologiske undergrupper.
ITT Population
CI = konfidensinterval; ITT = intent- to- treat; N = samlet populationsstørrelse. a Statistisk signifikans for non- inferiøriteten, med hele konfidensintervallet for HR pænt under 1. 17645 for non- inferiøriteten margin (p <. 001).
CI = confidence interval; ITT = intent-to-treat; N = total population size. a Statistically significant for noninferiority, with the entire confidence interval for HR well below the 1.17645 noninferiority margin (p < 0.001).
Kaplan Meier kurver over total overlevelse efter histologi
32 Kaplan Meier Plots of Overall Survival by Histology
Patienterne behøvede ligeledes mindre erythropoietin/ darbopoietin (10, 4% mod 18, 1%, p > 0, 001), G- CSF/ GM- CSF (3, 1% mod 6, 1%, p=0, 004) og midler med jern (4, 3 5 mod 7, 0%, p=0, 021).
Patients also required lower administration of erythropoietin/ darbopoietin (10.4% versus 18.1%, p < 0.001), G-CSF/ GM-CSF (3.1% versus 6.1%, p=0.004), and iron preparations (4.3% versus 7.0%, p=0.021).
32 clearance er 91, 8 ml/ min, og halveringstiden i plasma er 3, 5 timer hos patienter med normal nyre - funktion (kreatinin- clearance på 90 ml/ min).
Pemetrexed total systemic clearance is 91.8 ml/ min and the elimination half-life from plasma is 3.5 hours in patients with normal renal function (creatinine clearance of 90 ml/ min).
Pemetrexed var hverken mutagent i in vitro- testen for kromosomafvigelse hos kinesiske hamstere eller i Ames- testen.
33 Pemetrexed was not mutagenic in either the in vitro chromosome aberration test in Chinese hamster ovary cells, or the Ames test.
33 For opbevaringsforhold for det rekonstituerede lægemiddel, se sektion 6. 3.
For storage conditions of the reconstituted medicinal product see section 6.3.
6. 6 Regler for destruktion og anden håndtering
34 6.6 Special precautions for disposal and other handling