natgillin/translations-raw huggingface dataset:
Uden for EU fortsætter virksomheden dog med at undersøge brugen af Opaxio ved adskillige kræfttyper, herunder æggestokkræft, øsofaguskræft og ikke-småcellet lungekræft. 
However, outside the EU, the company is continuing to study Opaxio in several cancers including ovarian, oesophageal and non-small cell lung cancer.
Hvad forventedes Opaxio anvendt til? 
What was Opaxio expected to be used for?
Hvilke konsekvenser har tilbagetrækningen for patienter, der deltager i kliniske undersøgelser med Opaxio eller i programmer for anvendelse af Opaxio med særlig udleveringstilladelse? 
What are the consequences of the withdrawal for patients in clinical trials or compassionate use programmes using Opaxio?
Hvordan forventes Opaxio at virke? 
How is Opaxio expected to work?
Det indeholder det aktive stof paclitaxel poliglumex. 
It contains the active substance paclitaxel poliglumex.
Det forventes, at det aktive stof i Opaxio, paclitaxel poliglumex, omdannes til paclitaxel i kræftcellerne. 
The active substance in Opaxio, paclitaxel poliglumex, is expected to be converted into paclitaxel in the cancer cells.
I Opaxio er paclitaxel forbundet med poliglumex for at gøre det mere opløseligt. 
In Opaxio, paclitaxel is attached to poliglumex to make it more soluble.
Udvalget delte ikke virksomhedens opfattelse af, at undersøgelsen viste, at Opaxio var mindst lige så effektivt som sammenligningslægemidlerne, eftersom det ikke fremgik klart, at sammenligningslægemidlerne selv var effektive hos den type patienter, der deltog i hovedundersøgelsen. 
The company's view that the study showed that Opaxio was as least as good as the comparators was not accepted by the Committee because it was not clear that the comparators themselves were effective in the type of patients involved in the main study.
Opaxio er et pulver, der anvendes til at fremstille en infusionsvæske, opløsning (drop i en vene). 
Opaxio is a powder that is made up into a solution for infusion (drip into a vein).
ECOG-performancestatus er en skala, der viser, hvor syg en kræftpatient er. En performancestatus på 2 betyder, at patienten kan klare sig selv uden hjælp, men er for syg til at udføre nogen form for arbejde. 
A performance status of 2 means that the patient can take care of him or herself without help but is too ill to do any work.
På baggrund af gennemgangen af dataene og virksomhedens besvarelse af CHMP's liste med spørgsmål på tidspunktet for tilbagetrækningen af ansøgningen havde CHMP visse betænkeligheder og var af den foreløbige opfattelse, at Opaxio ikke kunne have været godkendt som førstevalgsbehandling til patienter med fremskreden ikke-småcellet lungekræft, som har en ECOGperformancestatus på 2. 
Based on the review of the data and the company's response to the CHMP list of questions, at the time of the withdrawal, the CHMP had some concerns and was of the provisional opinion that Opaxio could not have been approved for the first-line treatment of patients with advanced non-small cell lung cancer who have an ECOG performance status of 2.
Den 21. september 2009 meddelte CTI Life Sciences Ltd officielt Udvalget for Humanmedicinske Lægemidler (CHMP), at virksomheden ønsker at trække sin ansøgning om markedsføringstilladelse tilbage for Opaxio som førstevalgsbehandling til patienter med fremskreden ikke-småcellet lungekræft, som har en ECOG-performancestatus på 2. 
On 21 September 2009, CTI Life Sciences Ltd officially notified the Committee for Medicinal Products for Human Use (CHMP) that it wishes to withdraw its application for a marketing authorisation for Opaxio, for the first-line treatment of patients with advanced non-small cell lung cancer who have an ECOG performance status of 2.
Virksomheden fremlagde resultaterne af en hovedundersøgelse, der omfattede 477 patienter med fremskreden ikke-småcellet lungekræft og en ECOG-performancestatus på 2. 
The company presented results of one main study involving 477 patients with advanced non-small cell lung cancer and a performance status of 2.
Opaxio forventedes anvendt til patienter med fremskreden ikke-småcellet lungekræft, som har en ECOG-performancestatus på 2. 
Opaxio was expected to be used in patients with advanced non-small cell lung cancer who have an ECOG performance status of 2.
CHMP bemærkede, at hovedundersøgelsen ikke viste Opaxios virkning hos patienter med fremskreden ikke-småcellet lungekræft, som har en ECOG-performancestatus på 2. 
The CHMP noted that the main study did not show that Opaxio was effective in patients with advanced non-small cell lung cancer who have an ECOG performance status of 2.
Som konklusion blev følgende harmoniserede indikationer vedtaget for Femara: 
In conclusion, the following harmonised indications were adopted for Femara:
Samlet resumé af den videnskabelige vurdering af Femara og relaterede navne (se bilag I) 
Overall summary of the scientific evaluation of Femara and associated names (see Annex I)
CHMP flyttede angivelsen fra punkt 4.4 til punkt 5.1. 
The CHMP moved the statement from Section 4.4 to Section 5.1.
Der blev derfor indledt en henvisning i henhold til artikel 30, stk. 2, i direktiv 2001/83/EF, som ændret, med henblik på afklaring af disse divergenser og harmonisering af produktoplysningerne i hele EU. 
A referral under Article 30(2) of Directive 2001/83/EC, as amended was therefore triggered to resolve these divergences and thus harmonise the product information (PI) across the EU.
Desuden anses letrozol ikke for at have et smalt terapeutisk indeks. 
In addition, letrozole is not considered to have a narrow therapeutic index.
Vedrørende “invasiv” er det ikke sædvanlig praksis at ordinere aromatasehæmmere til patienter uden en invasiv komponent. 
Regarding “invasive”, it is not common practice to prescribe aromatase inhibitors to patients with no invasive component.
Vedrørende børn er invasiv mammacancer ekstremt sjældent hos børn og unge, men er blevet beskrevet. 
Regarding children, invasive breast cancer is extremely rare in children and adolescents but has been reported.
Øvrige punkter 
Other sections
CHMP godkendte dagsdosen 2,5 mg til voksne på grundlag af flere dosisfastlæggelsesundersøgelser. 
The CHMP endorsed the 2.5 mg daily dose in adults, based on several dose-finding studies.
CHMP anså det derfor for berettiget at indskrænke indikationen med betegnelsen “invasiv”. 
The CHMP therefore considered it justified to qualify the indication with “invasive”.
Dette gjaldt navnlig for punkt 4.8 - Bivirkninger, hvor ordlyden blev afkortet og beskåret væsentligt. 
In particular, for Section 4.8 - Undesirable Effects, the wording was significantly shortened and condensed.
Der er ikke påvist virkning hos patienter med hormonreceptornegativ mammacancer.” 
Efficacy has not been demonstrated in patients with hormone receptor negative breast cancer.”
CHMP tilføjede derfor en erklæring om effekter på knoglerne i forbindelse med anvendelse af Femara. 
The CHMP therefore added a statement regarding bone effects associated with the use of Femara.
CHMP fandt gennemgang af kliniske databaser uegnet som middel til at vurdere risikoen for interaktioner eller vurdere rapporter om manglende interaktion, og slettede derfor omtalen af sådanne gennemgange. 
The CHMP considered that reviews of clinical databases are poorly suited to assess the risk for interactions or to assess reports of lack of interaction and therefore removed references to these reviews.
Endvidere bemærkede udvalget, at der ikke er udført undersøgelser vedrørende DCIS (duktalt carcinoma in situ) eller LCIS (lobulært carcinoma in situ). 
In addition, no studies on DCIS (ductal carcinoma in situ) or LCIS (lobular carcinoma in situ) patients have been performed.
Indikationen neoadjuverende (præoperativ) behandling repræsenterede den største afvigelse mellem de nationalt godkendte produktresuméer, idet den blev godkendt i nogle medlemsstater i 2001, mens ansøgningen i andre stater blev trukket tilbage, primært fordi neoadjuverende endokrin behandling på daværende tidspunkt ikke var valideret som begreb, og fordi hovedundersøgelsens resultater for adjuverende behandling endnu ikke forelå. 
The neoadjuvant (pre-operative) treatment indication represented the major deviation across the nationally approved SmPCs, as it was approved in some member states in 2001 but the application was withdrawn in others, primarily because neoadjuvant endocrine treatment was not a validated concept at the time and because the results of the pivotal adjuvant study were not yet available.
Der er ikke behov for en kontraindikation hos sådanne patienter, men CHMP indsatte en forsigtighedsregel. 
While a contraindication in these patients was not warranted, the CHMP inserted a precaution.
CHMP indsatte i stedet en advarsel i punkt 4.4 om, at der savnes sikkerhedsdata for patienter med væsentligt nedsat organfunktion. 
The CHMP instead included a warning in Section 4.4 stating that safety data in patients with significant organ impairment are lacking.
Desuden er det essentielt at undgå graviditet under behandlingen med letrozol på grund af risikoen for embryo- og føtotoksicitet. 
In addition, it is essential to avoid pregnancy during letrozole therapy because of the risk of embryotoxicity and foetotoxicity.
Letrozol må således forventes at have potentiale for negative effekter på embryoet og føtus, hvilket bekræftes af undersøgelserne hos drægtige rotter og kaniner. 
Letrozole is thus predicted to have a potential for adverse effects on the embryo-foetus, as confirmed by studies in pregnant rats and rabbits.
CHMP tilføjede desuden en advarsel om, at østrogener og/eller tamoxifen kan nedsætte plasmaniveauet af letrozol og derved forringe dets farmakologiske virkning, hvorfor koadministration bør undgås. 
The CHMP also added a warning that oestrogens and/or tamoxifen may reduce letrozole plasma levels, thus reducing its pharmacological action, and that co-administration should therefore be avoided.
CHMP gennemgik potentialet for interaktion med en række stoffer, herunder cimetidin og andre midler mod kræft, samt betydningen af CYP2A6 og CYP3A4 i metaboliseringen af letrozol. 
The CHMP reviewed the potential for interaction of a number of substances, including cimetidine and anti-cancer agents, as well as the role played by CYP2A6 and CYP3A4 in the metabolism of letrozole.
I punkt 5.1 - Farmakodynamiske egenskaber blev ordlyden forkortet væsentligt og fokuseret på information, der er relevant for den ordinerende læge med henblik på de godkendte indikationer. 
For Section 5.1Pharmacodynamic Properties, the wording was substantially shortened to focus on information relevant to the prescriber for the approved indications.
Vedrørende præoperativ anvendelse af letrozol ved negativ eller ukendt receptorstatus anså CHMP en kontraindikation for unødvendig, da der allerede er redegjort fyldestgørende herfor i punkt 4.4. 
Regarding the pre-operative use of letrozole if receptor status is negative or unknown, the CHMP considered a contraindication to be unnecessary, as this is already sufficiently explained in Section 4.4.
CHMP fremhævede hovedundersøgelsen vedrørende indikationen adjuverende behandling, BIG 198, der var koordineret af samarbejdsgruppen IBCSG (International Breast Cancer Study Group) og moderorganisationen BIG (Breast International Group), og som specifikt udelukkede patienter, der ikke har fået bekræftet diagnosen invasiv mammacancer. 
The CHMP noted the pivotal study for the adjuvant treatment indication, BIG 1-98, coordinated by the collaborative group IBCSG (International Breast Cancer Study Group) and the parent organization BIG (Breast International Group), which specifically excluded patients who did not have a confirmed diagnosis of invasive breast cancer.
Desuden blev der tilføjet en erklæring om de manglende undersøgelser af anvendelse af Femara ved brystkræft hos mænd. 
A statement on the absence of studies on the use of Femara in male breast cancer was also added.
Femara indeholder letrozol, der er en aromatasehæmmer, som hæmmer omdannelsen af androgener til østrogener. 
Femara contains letrozole, an aromatase inhibitor which inhibits the conversion of androgens to oestrogens.
Vedrørende adjuverende og forlænget adjuverende behandling viser undersøgelserne, at virkningen blev opretholdt i den mediane behandlingsvarighed på fem år. 
Regarding adjuvant and extended adjuvant treatment, studies show that efficacy was sustained over the median duration of 5 years of treatment.
Videnskabelige konklusioner og begrundelse for ændringen af produktresuméet, etiketteringen og indlægssedlen, fremlagt af Det Europæiske Lægemiddelagentur 
Scientific conclusions and grounds for amendment of the summary of product characteristics, labelling and package leaflet presented by the European Medicines Agency
CHMP anså endvidere oplysningerne om behandlingsvarigheden med tamoxifen for at være berettiget, baseret på undersøgelser, hvor letrozol blev administreret efter fem år med adjuverende tamoxifen. 
The CHMP also considered information on the treatment duration with tamoxifen to be justified, based on studies in which letrozole was administered after 5 years of adjuvant tamoxifen.
Hos kvinder med frakturer og /eller osteoporose i anamnesen var frekvensen af frakturer højere end hos kvinder uden en sådan anamnese, uanset behandlingen. 
Women with a history of fractures and/or osteoporosis experienced higher rates of bone fractures than women without such a history, irrespective of treatment.
Vedrørende behandlingsvarigheden var det CHMP's opfattelse, at undersøgelserne viser, at behandlingen med Femara bør fortsætte, indtil der er tegn på yderligere progression af sygdommen. 
Regarding duration of treatment, the CHMP considered that studies show that Femara treatment should be continued until further progression of disease becomes evident.
Endelig indsatte CHMP en anbefaling om at undgå koadministration af Femara med tamoxifen, andre antiøstrogener eller østrogener. 
Finally, the CHMP inserted a statement advising against the co-administration of Femara with tamoxifen, other anti-oestrogens or oestrogens.
CHMP anså betegnelsen “hormonafhængig” for berettiget, da letrozol er uden virkning på hormonreceptornegativ mammacancer. 
The CHMP considered the term “hormone-dependent” to be justified, as letrozole has no efficacy in hormone receptor negative breast cancer.
Der er ikke udført undersøgelser ved DCIS eller LCIS af forlænget adjuverende behandling med aromatasehæmmere efter tamoxifen, og der er ikke grund til at antage, at virkningsmekanismen ved forlænget adjuverende behandling er anderledes end ved adjuverende behandling. 
No studies have been performed in DCIS or LCIS on the use of extended adjuvant aromatase inhibitors after tamoxifen and there is no reason to suggest a different mechanism of action in the extended adjuvant setting compared with the adjuvant setting.
CHMP konkluderede derfor, at de foreliggende data, herunder oplysninger om langtidsopfølgning, er tilstrækkelige til at underbygge indikationen neoadjuverende (præoperativ) behandling for Femara, navnlig med henblik på mindskelse af størrelsen af hormonreceptorpositive tumorer for at muliggøre brystbevarende operation eller gøre inoperable tumorer operable. 
The CHMP therefore concluded that the current data, including long-term follow-up information, is sufficient to support the neoadjuvant (pre-operative) treatment indication for Femara, in particular with the aim to down-size hormone receptor-positive tumours to allow BCS or to allow inoperable tumours to become operable.
For de resterende punkter i produktresuméet vedtog CHMP en harmoniseret ordlyd i overensstemmelse med de nationalt godkendte produktresuméer, dog med mindre ændringer. 
For the remaining sections, the CHMP adopted a harmonised wording in line with the nationally approved SmPCs, although minor revisions were made.
I beskrivelsen af udvalgte bivirkninger valgte CHMP at adskille dem efter indikationerne metastatisk, adjuverende og forlænget adjuverende. 
Regarding the description of selected adverse reactions, the CHMP agreed to separate the metastatic, adjuvant and extended adjuvant indications.
Desuden tilføjedes en anbefaling om at undgå anvendelse af Femara til patienter med galaktoseintolerans, svær laktasemangel eller glukose-galaktose-malabsorption. 
A statement recommending against the use of Femara for patients with problems of galactose intolerance, severe lactase deficiency or glucose-galactose malabsorption was also added.
Vedrørende nedsat nyrefunktion tog CHMP den foreliggende farmakokinetiske rapport til efterretning og konstaterede, at letrozol hovedsagelig elimineres ved hepatisk metabolisering, og at den renale clearance er rapporteret at være under 5 %. 
Regarding renal impairment, the CHMP noted the available pharmacokinetics report and observed that letrozole is mainly cleared by the hepatic metabolism, with renal clearance reported to be less than 5%.
Hvad angår brystkræft hos mænd bemærkede CHMP, at der ikke findes kliniske undersøgelser eller specifikke systematiske undersøgelser af anvendelse af Femara ved brystkræft hos mænd. 
Regarding male breast cancer, the CHMP noted the absence of clinical trials or specific systematic investigation on the use of Femara in male breast cancer.
CHMP bemærkede, at elimineringen af metabolitter må forventes at ske langsommere hos patienter med nedsat nyrefunktion, men at de foreliggende data viser, at dette ikke medførte forringet sikkerhedsprofil eller ændret farmakokinetik hos patienter med svært nedsat nyrefunktion. 
The CHMP noted that while elimination of metabolites is expected to be slower in patients with renal impairment, the available data show that this did not affect the safety profile and did not alter pharmacokinetics in patients with severe renal impairment.
CHMP konkluderede, at der for patienter med CrCl  10 ml/min ikke er behov for særlige advarsler eller anbefalinger om dosisjustering. 
The CHMP concluded that no specific warnings or dose adjustments recommendations are needed for patients with CrCl  10 ml/min.
Vedrørende nedsat leverfunktion fandt CHMP det uhensigtsmæssigt med en streng kontraindikation af letrozol, som er en potentielt livsreddende behandling med en forholdsvis godartet sikkerhedsprofil. 
Regarding hepatic impairment, the CHMP considered that a strict contraindication is not appropriate for letrozole, which is a potentially life-saving treatment with a relatively benign safety profile.
Dette har medført suboptimal virkning og høj forekomst af menopausale symptomer såsom hedeture, fordi den perimenopausale status har været utilstrækkelig til at undertrykke tilbagekoblingssløjfen for østrogensyntesen. 
As a result, efficacy was suboptimal and high rates of menopausal symptoms such as hot flushes occurred, as their perimenopausal status was insufficient to suppress the feedback loop of oestrogen synthesis.
Letrozol hæmmer det enzym, der medvirker ved syntese af østrogener, som er nødvendige for den embryo-føtale udvikling. 
Letrozole inhibits the enzyme involved in the synthesis of oestrogens, which are required for proper embryo and foetal development.
Tabellen over bivirkninger blev opstillet i overensstemmelse med vejledningen for produktresuméer, og flere bivirkninger blev flyttet til en mere passende systemorganklasse. 
The adverse drug reactions table was structured according to the SmPC guideline and several ADRs were relocated under more appropriate system organ class.
CHMP gennemgik alle foreliggende data og tog i betragtning, at letrozol har vist sig signifikant overlegent over for tamoxifen med hensyn til klinisk responsrate, mammografisk responsrate, responsrate ved ultralydsskanning af mammae og andel af brystbevarende kirurgiske indgreb (BCS). 
The CHMP reviewed all available data and considered that letrozole has shown significant superiority to tamoxifen in clinical response rate, mammographic response rate, breast ultrasound response rate and rate of breast-conserving surgery (BCS).
Vedrørende behandling af ældre fandt CHMP ikke, at der er behov for dosisjustering, baseret på analyser af virkning og sikkerhed i alle hovedundersøgelser med Femara. 
Regarding use in elderly, the CHMP did not consider dose adjustment to be required, based on analyses of efficacy and safety conducted for all pivotal studies with Femara.
Vedrørende effekter på knoglerne gennemgik CHMP undersøgelser, der viser, at langvarig anvendelse af Femara er forbundet med signifikant højere forekomst af osteoporose og signifikant højere forekomst af frakturer end med tamoxifen (som adjuverende behandling) eller med placebo (som forlænget adjuverende behandling). 
Regarding bone effects, the CHMP reviewed data from studies showing that long-term use of Femara is associated with a significantly higher rate of osteoporosis and a significantly higher rate of bone fractures than tamoxifen (adjuvant setting) or placebo (extended adjuvant setting).
CHMP indsatte en advarsel om postmenopausal endokrin status, da undersøgelserne har vist, at virkningen er suboptimal og bivirkningerne hyppigere og sværere hos kvinder med perimenopausal status. 
The CHMP introduced a warning regarding postmenopausal endocrine status, as studies have shown sub-optimal efficacy and increased frequency and severity of adverse events in women with perimenopausal status.
Femara blev sat på listen over produkter, som skal have opdateret produktresuméet, fordi medlemsstaterne har truffet divergerende afgørelser vedrørende godkendelse af produktet. 
Femara was included in the list of products for Summary of Product Characteristics (SmPC) harmonisation, due to the divergent national decisions taken by Member States concerning the authorisation of the above-mentioned product.
CHMP konkluderede, at der er væsentlige sikkerhedsmæssige betænkeligheder, som giver belæg for en kontraindikation hos præmenopausale kvinder, specielt kvinder med præmenopausal endokrin status. 
The CHMP concluded that there are significant safety concerns warranting a contraindication in premenopausal women, specifically in women of premenopausal endocrine status.
CHMP definerede målpopulationen som patienter med manifest postmenopausal status og patienter med ER-positiv tumor, patienter, hvis tumor at HER-2- (human epidermal vækstfaktor receptor 2) negativ, patienter, der ikke tåler eller ikke ønsker neoadjuverende kemoterapi, samt patienter, der ikke er egnede til øjeblikkelig operation. 
The CHMP defined the target patient population as women of established postmenopausal status and patients with ER-positive tumours, patients whose tumours are HER-2 (Human Epidermal Growth Factor Receptor 2) negative and patients who are unable to tolerate or who refuse to take neoadjuvant chemotherapy as well as patient for whom immediate surgery is not an option.
Vedrørende nedsat nyrefunktion konstaterede CHMP, at der kun foreligger meget begrænsede oplysninger om patienter med kreatininclearance under 10 ml/min., og indsatte derfor en forsigtighedsregel fra sådanne patienter. 
Regarding renal impairment, the CHMP noted that there is very limited information about patients whose creatinine clearance is below 10 ml/min and therefore agreed on a precaution for these patients.
CHMP bemærkede, at der ikke findes fyldestgørende kliniske undersøgelser hos gravide kvinder, at der er indberettet enkeltstående tilfælde af fødselsdefekter hos gravide kvinder eksponeret for Femara, og at de ikke-kliniske undersøgelser har vist, at letrozol er embryotoksisk og føtotoksisk. 
The CHMP noted the absence of adequate clinical trials in pregnant women and that isolated cases of birth defects have been reported in pregnant women exposed to Femara, while nonclinical studies have shown that letrozole is embryotoxic and foetotoxic.
I mangel af kliniske undersøgelser konkluderede CHMP derfor, at der ikke er dokumenteret sikkerhed og virkning af Femara hos denne patientgruppe. 
In the absence of clinical trials, the CHMP therefore concluded that the safety and efficacy of Femara in this population is not established.