natgillin/translations-raw huggingface dataset:
De sekundære endepunkter omfattede sikkerhed, objektiv tumorresponsrate, overlevelse, sygdomsrelaterede symptomer og livskvalitet.
Secondary endpoints included safety, objective tumour response rate, overall survival, disease-related symptoms, and quality of life.
Det primære endepunkt for studiet var PFS evauleret ved RECIST (Response Evaluation Criteria in Solid Tumours).
The primary endpoint for the study was PFS evaluated by RECIST (Response Evaluation Criteria in Solid Tumors).
• Feber, ondt i halsen, mundsår pga. infektioner (tegn på et lavt antal hvide blodlegmer,
• Fever, sore throat, mouth ulcers due to infections (signs of low level of white blood cells,
• Feber, hududslæt, smerter og inflammation (betændelseslignende reaktion) i led samt træthed, appetitløshed, kvalme, gulsot (gullig hud), smerter i den øverste højre del af maven, lys afføring, mørk urin (kan være tegn på opblussen af hepatitis B-infektion)
• Fever, skin rash, joint pain and inflammation, as well as tiredness, loss of appetite, nausea, jaundice (yellowing of the skin), pain in the upper right abdomen, pale stools, dark urine (may be signs of hepatitis B reactivation)
Ved tidspunktet for data cut-off, var median-varigheden af behandling 27,5 uger (interval 2,0-165,7) i everolimus + exemestan-armen, 20 uger (1,3-145,0) i everolimus-armen og 26,7 uger (1,4-177,1) i capecitabin-armen.
At the time of data cut-off, the median duration of treatment was 27.5 weeks (range 2.0-165.7) in the everolimus + exemestane arm, 20 weeks (1.3-145.0) in the everolimus arm, and 26.7 weeks (1.4-177.1) in the capecitabine arm.
Overfølsomhed over for det aktive stof, andre rapamycin-derivater eller over for et eller flere af hjælpestofferne anført i pkt.
Hypersensitivity to the active substance, to other rapamycin derivatives or to any of the excipients listed in section 6.1.
Demografiske karakteristika og sygdomskarakteristika var generelt velbalancerede (medianalder 63 år [interval 22 til 86], 76 % kaukasier, behandling med somatostatinanaloger (SSA) i anamnesen).
Demographics and disease characteristics were generally balanced (median age 63 years [range 22 to 86], 76% Caucasian, history of prior somatostatin analogue [SSA] use).
Afinitor indeholder: Aktivt stof: everolimus.
What Afinitor contains The active substance is everolimus.
• Tør mund
• Dry mouth
Median total overlevelse (måneder) (95% CI) Median total overlevelse
Median overall survival (months) (95% CI) Median overall survival
De sekundære endepunkter omfattede total overlevelse (OS), objektiv responsrate, rate for klinisk fordel, sikkerhed, ændring i livskvalitet (QoL) og tid til forværring af ECOG PS (Eastern Cooperative Oncology Group performance status).
Secondary endpoints included overall survival (OS), objective response rate, clinical benefit rate, safety, change in quality of life (QoL) and time to ECOG PS (Eastern Cooperative Oncology Group performance status) deterioration.
Der er observeret tilfælde af nyresvigt (inklusive akut nyresvigt), nogle med letalt udfald, hos patienter behandlet med Afinitor (se pkt.
Cases of renal failure (including acute renal failure), some with a fatal outcome, have been observed in patients treated with Afinitor (see section 4.8).
Lægemidler, hvis plasmakoncentration kan blive påvirket af everolimus Baseret på in vitro resultater, er det usandsynligt, at PgP, CYP3A4 og CYP2D6 hæmmes ved de systemiske koncentrationer, der opnås efter daglig oral dosis af 10 mg. Hæmning af CYP3A4 og PgP i tarmen kan dog ikke udelukkes.
Agents whose plasma concentration may be altered by everolimus Based on in vitro results, the systemic concentrations obtained after oral daily doses of 10 mg make inhibition of PgP, CYP3A4 and CYP2D6 unlikely.
Hvis en patient har brug for samtidig administration af potente CYP3A4-hæmmere, bør det overvejes at øge Afinitor-dosis fra 10 mg/dag til 20 mg/dag med stigninger på 5 mg eller mindre på dag 4 og 8 og derefter opstart af behandling med induktor.
If patients require co-administration of a potent CYP3A4 inducer, an Afinitor dose increase from 10 mg daily up to 20 mg daily should be considered using 5 mg increments or less applied on Day 4 and 8 following start of the inducer.
Sådan skal du tage Afinitor
How to take Afinitor
De hyppigste bivirkninger af Grad 3-4 (hyppighed ≥1/100 til <1/10) var stomatitis, anæmi, hyperglykæmi, infektioner, træthed, diarré, pneumonitis, asteni, trombocytopeni, neutropeni, dyspnø, proteinuri, lymfopeni, hæmoragi, hypofosfatæmi, udslæt, hypertension, pneumoni, forhøjet alaninaminotransferase (ALAT), forhøjet aspartat-aminotransferase (ASAT) og diabetes mellitus.
The most frequent Grade 3-4 adverse reactions (incidence ≥1/100 to <1/10) were stomatitis, anaemia, hyperglycaemia, infections, fatigue, diarrhoea, pneumonitis, asthenia, thrombocytopenia, neutropenia, dyspnoea, proteinuria, lymphopenia, haemorrhage, hypophosphataemia, rash, hypertension, pneumonia, alanine aminotransferase (ALT) increased, aspartate aminotransferase (AST) increased and diabetes mellitus.
• Spontan blødning eller blå mærker (tegn på lavt niveau af blodplader, også kendt som trombocytopeni)
• Spontaneous bleeding or bruising (signs of low level of platelets, also known as thrombocytopenia)
Monitorering af kolesterol og triglycerider i blodet før opstart af behandling med Afinitor og periodisk herefter samt passende medicinsk behandling anbefales.
Monitoring of blood cholesterol and triglycerides prior to the start of Afinitor therapy and periodically thereafter, as well as management with appropriate medical therapy, is recommended.
I kliniske studier og spontane rapporter modtaget efter markedsføring er everolimus blevet associeret med tilfælde af PJP/PCP, hvoraf nogle var med letal udgang (se punkt 4.4).
In clinical studies and post-marketing spontaneous reports, everolimus has been associated with cases of PJP/PCP, some with fatal outcome (see section 4.4).
Inklusive (meget almindelig) stomatitis, (almindelig) aftøs stomatitis, mund- og tungeulceration og (ikke almindelig) glossodyni, glossitis e
Includes (very common) stomatitis, (common) aphthous stomatitis, mouth and tongue ulceration and (uncommon) glossodynia, glossitis e
Progressive neuroendokrine tumorer udgået fra pancreas (pNET) RADIANT-3 (studier CRAD001C2324), et fase-III, multicenter, randomiseret, dobbeltblindet studie af Afinitor plus bedste understøttende behandling (BSC) versus placebo samt BSC hos patienter med fremskreden pNET, viste en statistisk signifikant klinisk fordel ved behandling med Afinitor i forhold til placebo, med en 2,4 gange forlængelse af den mediane progressionsfri overlevelse (PFS) (11,04 måneder versus 4,6 måneder) (HR 0,35; 95% CI: [0,27; 0,45]; p<0,0001) (se tabel 5 og figur 3).
Advanced neuroendocrine tumours of pancreatic origin (pNET) RADIANT-3 (study CRAD001C2324), a phase III, multicentre, randomised, double-blind study of Afinitor plus best supportive care (BSC) versus placebo plus BSC in patients with advanced pNET, demonstrated a statistically significant clinical benefit of Afinitor over placebo by a 2.4-fold prolongation of median progression-free-survival (PFS) (11.04 months versus 4.6 months), (HR 0.35; 95% CI: 0.27, 0.45; p<0.0001) (see Table 5 and Figure 3).
Afinitor er indiceret til behandling af fremskreden hormonreceptorpositiv, HER2/neu-negativ brystcancer i kombination med exemestan hos postmenopausale kvinder uden symptomatisk, visceral sygdom efter recidiv eller progression efter en non-steroid aromatasehæmmer.
Hormone receptor-positive advanced breast cancer Afinitor is indicated for the treatment of hormone receptor-positive, HER2/neu negative advanced breast cancer, in combination with exemestane, in postmenopausal women without symptomatic visceral disease after recurrence or progression following a non-steroidal aromatase inhibitor.
Anvendelse af levende vacciner bør undgås under behandling med Afinitor (se pkt.
The use of live vaccines should be avoided during treatment with Afinitor (see section 4.4).
Naturlægemidler indeholdende perikon må ikke anvendes under behandling med everolimus.
Preparations containing St John's Wort should not be used during treatment with everolimus
I alt blev 416 patienter randomiseret 2:1 til at modtage Afinitor (n=277) eller placebo (n=139).
In total, 416 patients were randomised 2:1 to receive Afinitor (n=277) or placebo (n=139).
• Voldsom tørst, hyppig vandladning, øget appetit med vægttab, træthed (tegn på sukkersyge)
• Excessive thirst, high urine output, increased appetite with weight loss, tiredness (signs of diabetes)
Inklusive alle tilfælde inden for systemorganklassen “infektioner og parasitære sygdomme” inklusive (almindelig) pneumoni, urinvejsinfektion; (ikke almindelig) bronkitis, herpes zoster, sepsis, abscesser og isolerede tilfælde af opportunistiske infektioner [fx aspergillose, candidiasis, PJP/PCP og hepatitis B (se også pkt.
Includes all reactions within the ‘infections and infestations' system organ class including (common) pneumonia, urinary tract infection; (uncommon) bronchitis, herpes zoster, sepsis, abscess, and isolated cases of opportunistic infections [e.g. aspergillosis, candidiasis, PJP/PCP and hepatitis B (see also section 4.4)] and (rare) viral myocarditis b
Der er ikke behov for dosisjustering (se pkt.
Renal impairment No dose adjustment is required (see section 5.2).
• Stærkt nedsat vandladning (tegn på nyresvigt)
• Severely decreased urine output (sign of kidney failure)
Rate for klinisk fordel c n/a d e a
Clinical benefit rate c
Den mediane varighed af blindet forsøgsbehandling var 141 dage (interval 19-451 dage) for patienter, der fik everolimus, og 60 dage (interval 21-295 dage) for dem, der fik placebo.
The median duration of blinded study treatment was 141 days (range 19-451 days) for patients receiving everolimus and 60 days (range 21-295 days) for those receiving placebo.
• Tørst, nedsat vandladning, mørk urin, tør, rød hud, irritabilitet (tegn på væskemangel)
• Thirst, low urine output, dark urine, dry flushed skin, irritability (signs of dehydration)
CYP3A4- og PgP-hæmmeres øgning af everolimus-koncentrationer Stoffer, der hæmmer CYP3A4 eller PgP, kan øge blodkoncentrationer af everolimus ved at nedsætte metabolismen eller effluksen af everolimus fra tarmcellerne.
CYP3A4 and PgP inhibitors increasing everolimus concentrations Substances that are inhibitors of CYP3A4 or PgP may increase everolimus blood concentrations by decreasing metabolism or the efflux of everolimus from intestinal cells.
Det anbefales at monitorere faste-serum-glucose før opstart af behandling med Afinitor og periodisk derefter.
Monitoring of fasting serum glucose is recommended prior to the start of Afinitor therapy and periodically thereafter.
• Hævelse i ansigtet, rundt om øjnene, munden og inden i munden og/eller halsen samt tungen med vejrtrækningsbesvær eller synkebesvær (også kendt som angioødem).
• Swelling of the face, around the eyes, mouth, and inside the mouth and/or throat, as well as the tongue and difficulty breathing or swallowing (also known as angioedema), may be signs of an allergic reaction
• Betændelse i slimhinden i munden, maven eller tarmene
• Inflammation of the inner lining of the mouth, stomach, gut
CYP3A4- og PgP-induktorers nedsættelse af everolimus-koncentrationer Stoffer, der inducerer CYP3A4 eller PgP, kan nedsætte blodkoncentrationer af everolimus ved at øge metabolismen eller effluks af everolimus ud af tarmcellerne.
CYP3A4 and PgP inducers decreasing everolimus concentrations Substances that are inducers of CYP3A4 or PgP may decrease everolimus blood concentrations by increasing metabolism or the efflux of everolimus from intestinal cells.
Ikke relevant e
n/a d e
De er præget med “5” på den ene side og “NVR” på den anden.
They are engraved with “5” on one side and “NVR” on the other.
• Halsbrand (dyspepsi)
• Heartburn (dyspepsia)
Censoreringstidspunkter Everolimus + BSC (n/N = 113/205) Placebo + BSC (n/N = 65/97)
Everolimus + BSC (n/N = 113/205) Placebo + BSC (n/N = 65/97)
Samtidig brug af angiotensin-konverteringsenzym (ACE)-hæmmere Hos patienter, der samtidig behandles med en ACE-hæmmer (fx ramipril), kan der være forhøjet risiko for angioødem (fx hævelse af luftvejene eller tungen med eller uden respiratorisk svækkelse) (se pkt.
Concomitant use of angiotensin-converting enzyme (ACE) inhibitors Patients taking concomitant ACE inhibitor (e.g. ramipril) therapy may be at increased risk for angioedema (e.g. swelling of the airways or tongue, with or without respiratory impairment) (see section 4.5).
Dosisjustering er normalt ikke påkrævet ved bivirkninger af Grad 1.
For adverse reactions of Grade 1, dose adjustment is usually not required.
De hyppigste bivirkninger (incidens ≥1/10) fra de samlede sikkerhedsdata var (efter faldende incidens): stomatitis, udslæt, træthed, diarré, infektioner, kvalme, nedsat appetit, anæmi, smagsforstyrrelser, pneumonitis, perifert ødem, hyperglykæmi, asteni, pruritus, vægttab, hyperkolesterolæmi, næseblod, hoste og hovedpine.
The most common adverse reactions (incidence ≥1/10) from the pooled safety data were (in decreasing order): stomatitis, rash, fatigue, diarrhoea, infections, nausea, decreased appetite, anaemia, dysgeusia, pneumonitis, oedema peripheral, hyperglycaemia, asthenia, pruritus, weight decreased, hypercholesterolaemia, epistaxis, cough and headache.
Prognostiske faktorer ved neuroendokrine tumorer udgået fra mave-tarm-kanalen eller lungerne Hos patienter med ikke-funktionelle neuroendokrine tumorer udgået fra mave-tarm-kanalen eller lungerne og med gode prognostiske baseline-faktorer, fx primærtumor udgået fra ileum og normale kromogranin A-værdier eller uden knoglepåvirkning, bør der foretages en individuel benefit/riskvurdering før opstart af behandling med Afinitor.
Prognostic factors in neuroendocrine tumours of gastrointestinal or lung origin In patients with non-functional gastrointestinal or lung neuroendocrine tumours and good prognostic baseline factors, e.g. ileum as primary tumour origin and normal chromogranin A values or without bone involvement, an individual benefit-risk assessment should be performed prior to the start of Afinitor therapy.
• Højt indhold af sukker i blodet (hyperglykæmi)
• High level of sugar in the blood (hyperglycaemia)
Den estimerede HR var 1,26 (90 % CI: 0,96; 1,66) for det vigtigste sekundære endepunkt PFS og var til fordel for capecitabin frem for everolimus + exemestan-kombinationsarmen, baseret på i alt 148 observerede PFS-hændelser.
For the key secondary endpoint PFS the estimated HR was 1.26 (90% CI: 0.96, 1.66) in favour of capecitabine over the everolimus + exemestane combination arm based on a total of 148 PFS events observed.
• Manglende smagssansen (ageusi)
• Loss of sense of taste (ageusia)
Mænds frugtbarhed Afinitor kan påvirke mænds frugtbarhed.
Male fertility Afinitor may affect male fertility.
• Udslæt, kløe, nældefeber, vejrtræknings- eller synkebesvær, svimmelhed (tegn på en alvorlig allergisk reaktion, også kendt som overfølsomhed)
• Rash, itching, hives, difficulty breathing or swallowing, dizziness (signs of serious allergic reaction, also known as hypersensitivity)
Det anbefales at foretage en komplet blodtælling før opstart af behandling med Afinitor og med jævne mellemrum herefter.
Monitoring of complete blood count is recommended prior to the start of Afinitor therapy and periodically thereafter.
Den mediane varighed af blindet forsøgsbehandling var 37,8 uger (interval 1,1-129,9 uger) for patienter, der fik everolimus, og 16,1 uger (interval 0,4-147,0 uger) for dem, der fik placebo.
The median duration of blinded study treatment was 37.8 weeks (range 1.1-129.9 weeks) for patients receiving everolimus and 16.1 weeks (range 0.4-147.0 weeks) for those receiving placebo.
Derfor frarådes samtidig behandling med Afinitor og potente hæmmere.
Hence, concomitant treatment of Afinitor and potent inhibitors is not recommended.
Det primære endepunkt for studiet var progressionsfri overlevelse (PFS) evalueret ved RECIST (Response Evaluation Criteria in Solid Tumours) baseret på investigators vurdering (lokal radiologi).
The primary endpoint for the study was progression-free survival (PFS) evaluated by RECIST (Response Evaluation Criteria in Solid Tumors), based on the investigator's assessment (local radiology).
Der blev rapporteret begrænset evidens for en PFSfordel hos en undergruppe af patienter med primærtumor udgået fra ileum (se pkt.
Limited evidence of PFS benefit was reported in the subgroup of patients with ileum as primary tumour origin (see section 5.1).
Stomatitis er den hyppigst rapporterede bivirkning hos patienter, der blev behandlet med Afinitor (se pkt.
Stomatitis is the most commonly reported adverse reaction in patients treated with Afinitor (see sections 4.4 and 4.8).
Grad 3 Midlertidig behandlingspause.
Grade 3 Temporary dose interruption.
De er præget med “LCL” på den ene side og “NVR” på den anden.
They are engraved with “LCL” on one side and “NVR” on the other.
• Stakåndethed, vejrtrækningsbesvær i liggende stilling, hævede fødder eller ben (tegn på hjertesvigt)
• Breathlessness, difficulty breathing when lying down, swelling of the feet or legs (signs of heart failure)
• Udslæt og smerter i håndflader eller fodsåler (hånd-fodsyndrom)
• Rash and pain on the palms of your hands or soles of your feet (hand-foot syndrome)
Studiets primære endepunkt var progressionsfri overlevelse (PFS), evauleret ved Response Evaluation Criteria in Solid Tumours (RECIST), baseret på en uafhængig radiologisk vurdering.
The primary endpoint for the study was progression-free survival (PFS) evaluated by Response Evaluation Criteria in Solid Tumors (RECIST), based on independent radiology assessment.
I alt 724 patienter blev randomiseret i forholdet 2:1 til kombinationen everolimus (10 mg dagligt) + exemestan (25 mg dagligt) (n=485) eller til placebo + exemestan (25 mg dagligt) (n=239).
A total of 724 patients were randomised in a 2:1 ratio to the combination everolimus (10 mg daily) + exemestane (25 mg daily) (n=485) or to the placebo + exemestane arm (25 mg daily) (n=239).
Log-rank p-værdi = <0,001
Log-rank p value = <0.001
RECORD-1 (studie CRAD001C2240), et fase III-, internationalt, randomiseret, dobbeltblindet multicenter-studie med sammenligning af everolimus 10 mg/dag og placebo, begge sammen med bedste understøttende behandling, blev udført med patienter med metastatisk renalcellekarcinom, hvis sygdom var progredieret under eller efter behandling (sunitinib, sorafenib eller både sunitinib og sorafenib) med VEGFR-TKI (vascular endothelial growth factor receptor tyrosine kinase inhibitor).
RECORD-1 (study CRAD001C2240), a phase III, international, multicentre, randomised, double-blind study comparing everolimus 10 mg/day and placebo, both in conjunction with best supportive care, was conducted in patients with metastatic renal cell carcinoma whose disease had progressed on or after treatment with VEGFR-TKI (vascular endothelial growth factor receptor tyrosine kinase inhibitor) therapy (sunitinib, sorafenib, or both sunitinib and sorafenib).
Antal patienter i fortsat risiko Afinitor
No. of patients still at risk Afinitor
De er præget med “UHE” på den ene side og “NVR” på den anden.
They are engraved with “UHE” on one side and “NVR” on the other.
Log-rank p-værdi = <0,0001
Log-rank p value = <0.0001
Immunsystemet Ikke almindelig
Immune system disorders
Median progressionsfri overlevelse (måneder) (95% CI)
Median progression-free survival (months) (95% CI)
• Forhøjet indhold af fedt (lipider) i blodet (hyperlipidæmi, forhøjede triglycerider)
• High level of lipids (fats) in the blood (hyperlipidaemia, raised triglycerides)
• Udflåd fra øjnene med kløe, rødme og hævelse
• Discharge from the eye with itching, redness and swelling
forårsage sår i munden og at sår udvikler sig.
cause mouth ulcers and sores to develop.
Almindelig Tør hud, neglelidelse, let hårtab, akne, erytem, onychoclasis, palmoplantar erytrodysæstesi-syndrom, eksfoliation, hudlæsioner
Common Dry skin, nail disorders, mild alopecia, acne, erythema, onychoclasis, palmar-plantar erythrodysaesthesia syndrome, skin exfoliation, skin lesion
Almindelig Proteinuri*, blod-kreatinin forhøjet, nyresvigt* Ikke almindelig
Common Proteinuria*, blood creatinine increased, renal failure* Uncommon Increased daytime urination, acute renal failure* Reproductive system and breast disorders Common Menstruation irregular e
Tid(uger)
Time (Weeks)
Samtidig brug af angiotensin-konverteringsenzym (ACE)-hæmmere Hos patienter, der samtidig behandles med en ACE-hæmmer (fx ramipril), kan der være forhøjet risiko for angioødem (se pkt.
Concomitant use of angiotensin-converting enzyme (ACE) inhibitors Patients taking concomitant ACE inhibitor (e.g. ramipril) therapy may be at increased risk for angioedema (see section 4.4).
Grad 2 Dosisjustering ikke nødvendig.
Grade 2 No dose adjustment required.
Der er dog observeret amenoré (sekundær amenoré og andre uregelmæssigheder i menstruationen) og associeret ubalance i luteiniserende hormon (LH)/follikelstimulerende hormon hos kvinder.
The potential for everolimus to cause infertility in male and female patients is unknown, however amenorrhoea (secondary amenorrhoea and other menstrual irregularities) and associated luteinising hormone (LH)/follicle stimulating hormone (FSH) imbalance has been observed in female patients.
Hvis toksicitet recidiverer ved Grad 2, afbrydes behandlingen indtil bedring til Grad 1.
If toxicity recurs at Grade 2, interrupt treatment until recovery to Grade 1.
• Åndenød (dyspnø)
• Breathlessness (dyspnoea)
Grad 3 Midlertidig behandlingspause indtil bedring til Grad 2 (≥1,25x10
Grade 3 Temporary dose interruption until recovery to Grade 2 (≥1.25x10
I alt blev 410 patienter randomiseret 1:1 til at få enten Afinitor 10 mg/dag (n=207) eller placebo (n=203).
In total, 410 patients were randomised 1:1 to receive either Afinitor 10 mg/day (n=207) or placebo (n=203).
BOLERO-6 (studie CRAD001Y2201), et tre-armet, randomiseret, open-label, fase II-studie med everolimus i kombination med exemestan versus everolimus alene versus capecitabin til behandling af postmenopausale kvinder med østrogenreceptor-positiv, HER2/neu-negativ, lokalt fremskreden, recidiverende eller metastatisk brystcancer efter recidiv eller progression på tidligere behandling med letrozol eller anastrozol.
BOLERO-6 (Study CRAD001Y2201), a three-arm, randomised, open-label, phase II study of everolimus in combination with exemestane versus everolimus alone versus capecitabine in the treatment of postmenopausal women with oestrogen receptor-positive, HER2/neu negative, locally advanced, recurrent, or metastatic breast cancer after recurrence or progression on prior letrozole or anastrozole.
Dosering Afinitor er tilgængelig i 2,5 mg, 5 mg og 10 mg tabletter til forskellige doseringsmuligheder.
Posology For the different dose regimens Afinitor is available as 2.5 mg, 5 mg and 10 mg tablets.
Meget almindelige (forekommer hos flere end 1 ud af 10 patienter)
Very common (may affect more than 1 in 10 people)
Hjælpestof, som behandleren skal være opmærksom på Hver tablet indeholder 297 mg lactose.
Excipient with known effect Each tablet contains 297 mg lactose.
I kliniske studier og post-marketing spontane rapporter er everolimus blevet forbundet med tilfælde af nyresvigt (inklusive letale tilfælde) og proteinuria.
In clinical studies and post-marketing spontaneous reports, everolimus has been associated with renal failure events (including fatal outcome) and proteinuria.