natgillin/translations-raw huggingface dataset:
Tages der højde for disse baseline-faktorer, blev hazard ratio for behandlingen 0,78 (95 % konfidensinterval [0,63 - 0,96], p = 0,0219), indikerende en 22 % risikoreduktion for død for patienter i Avastin + IFN alfa-2a-armen i forhold til IFN alfa-2a-armen.
Adjustment for these baseline factors resulted in a treatment hazard ratio of 0.78 (95% CI [0.63; 0.96], p=0.0219), indicating a 22% reduction in the risk of death for patients in the Avastin + IFN alfa-2a arm compared to IFN alfa-2a arm.
• røde øjne, små partikler eller pletter i synsfeltet (”flyvende fluer”), øjensmerter,
• Redness of the eye, small particles or spots in your vision (floaters), eye pain,
Der er observeret en øget hyppighed af alvorlig neutropeni, febril neutropeni eller infektion med eller uden alvorlig neutropeni (herunder nogle dødsfald) hos patienter, som blev behandlet med visse myelotoksiske kemoterapiregimer plus Avastin i forhold til kemoterapi alene.
Increased rates of severe neutropenia, febrile neutropenia, or infection with or without severe neutropenia (including some fatalities) have been observed in patients treated with some myelotoxic chemotherapy regimens plus Avastin in comparison to chemotherapy alone.
Hypertension resulterede sjældent i afbrydelse af Avastinbehandlingen eller hospitalsindlæggelse.
It rarely resulted in discontinuation of Avastin treatment or hospitalisation.
Hvis sygdomsprogressionen ikke forekom, medførte seponering af den ene komponent i studiemedicinen i erlotinib + Avastin-armen ikke seponering af den anden komponent jfr.
In the absence of PD, discontinuation of one component of study treatment in the erlotinib + Avastin arm did not lead to discontinuation of the other component of study treatment as specified in the study protocol.
CHF-bivirkninger af grad 3 eller højere var lidt hyppigere hos patienter i behandling med bevacizumab i kombination med kemoterapi end hos patienter, som blev behandlet med kemoterapi alene.
CHF Grade 3 or higher reactions were somewhat more frequent among patients receiving bevacizumab in combination with chemotherapy than in patients receiving chemotherapy alone.
Mulige risikofaktorer inkluderer planocellulær histologi, behandling med antireumatiske/antiinflammatoriske lægemidler, behandling med antikoagulantia, tidligere strålebehandling, Avastinbehandling, aterosklerose i anamnesen, central placering af tumor og kavernedannelse i tumorer før eller under behandling.
Possible risk factors include squamous cell histology, treatment with antirheumatic/anti-inflammatory substances, treatment with anticoagulants, prior radiotherapy, Avastin therapy, previous medical history of atherosclerosis, central tumour location and cavitation of tumours prior to or during therapy.
● alvorlige infektioner i huden eller i de dybereliggende lag under huden,
● serious infections of the skin or deeper layers under the skin,
Pædiatrisk population Sikkerheden og effekten af Avastin hos børn under 18 år er ikke klarlagt.
Paediatric population The safety and efficacy of Avastin in children less than 18 years old have not been established.
I et klinisk studie AVF2192g, som undersøgte Avastin i kombination med 5-fluoruracil/folininsyre, blev der inkluderet patienter med metastatisk kolorektalkræft, som ikke var kandidater til behandling med irinotecan.
In one clinical trial evaluating Avastin in combination with 5-fluorouracil/folinic acid, AVF2192g, patients with metastatic colorectal cancer who were not candidates for treatment with irinotecan were included.
I fire fase III-studier (AVF2119g, E2100, BO17708 og AVF3694g) hos patienter med metastatisk brystkræft blev der observeret CHF af grad 3 (NCI-CTCAE v. 3) eller højere hos op til 3,5 % af de patienter, som blev behandlet med Avastin i kombination med kemoterapi, sammenlignet med hos op til 0,9 % i kontrolarmene.
In four phase III trials (AVF2119g, E2100, BO17708 and AVF3694g) in patients with metastatic breast cancer CHF Grade 3 (NCI-CTCAE v.3) or higher was reported in up to 3.5% of patients treated with Avastin in combination with chemotherapy compared with up to 0.9% in the control arms.
**Randomiserede patienter med målbar sygdom ved baseline.
**Randomized Patients with Measurable Disease at Baseline.
Patienter, som får gastroinstestinale-vaginale fistler, kan også have tarmobstruktion, som kræver kirurgisk indgreb såvel som stomi.
Patients who develop GI-vaginal fistulae may also have bowel obstructions and require surgical intervention as well as diverting ostomies.
• allergiske reaktioner (symptomer kan være vejrtrækningsproblemer, ansigtsrødme, udslæt, lavt blodtryk eller højt blodtryk, lav iltmængde i blodet, brystsmerter eller kvalme/opkastning),
• allergic reactions (the signs may include difficulty breathing, facial redness, rash, low blood pressure or high blood pressure, low oxygen in your blood, chest pain, or nausea/vomiting),
Det primære endepunkt for dette studie var progressionsfri overlevelse (PFS), baseret på studieinvestigatorernes vurdering af sygdomsprogression.
The primary endpoint of this trial was progression free survival (PFS), based on trial investigators' assessment of disease progression.
Den kliniske effekt af Avastin, målt som PFS, blev observeret hos alle testede præspecificerede undergrupper (herunder sygdomsfrit interval, antal metastatiske foci, tidligere adjuverende kemoterapi og østrogenreceptorstatus (ER)).
The clinical benefit of Avastin as measured by PFS was seen in all pre-specified subgroups tested (including disease-free interval, number of metastatic sites, prior receipt of adjuvant chemotherapy and oestrogen receptor (ER) status).
Behandlingen med Avastin skal stoppes permanent, hvis du får
The administration of Avastin should be permanently discontinued if you develop
Sikkerhed og effekt af den anbefalede dosis (5 mg/kg legemsvægt hver 2. uge) hos patienter med metastatisk kolorektalkræft blev undersøgt i tre randomiserede, aktivt kontrollerede kliniske studier i kombination med fluoropyrimidinbaseret 1.-linjekemoterapi.
The safety and efficacy of the recommended dose (5 mg/kg of body weight every two weeks) in metastatic carcinoma of the colon or rectum were studied in three randomised, active-controlled clinical trials in combination with fluoropyrimidine-based first-line chemotherapy.
Patienter, behandlet med Avastin for persisterende, recidiverende eller metastatisk cervixcancer i kombination med paclitaxel og cisplatin, kan have en øget risiko for venøse tromboemboliske bivirkninger.
Patients treated for persistent, recurrent, or metastatic cervical cancer with Avastin in combination with paclitaxel and cisplatin may be at increased risk of venous thromboembolic events.
I studie JO25567 blev hypertension af alle grader observeret hos 77,3 % af patienterne, som fik Avastin i kombination med erlotinib, som 1.-linje behandling af ikke-planocellulær NSCLC med EGFR- aktiverende mutationer, sammenlignet med 14,3 % af patienterne, som blev behandlet med erlotinib alene.
In study JO25567, all grade hypertension was observed in 77.3% of the patients who received Avastin in combination with erlotinib as first-line treatment for non-squamous NSCLC with EGFR activating mutations, compared to 14.3% of patients treated with erlotinib alone.
I en retrospektiv, eksplorativ analyse af data fra 13 afsluttede, randomiserede studier hos patienter med forskellige tumortyper, udviklede 3 ud af 91 patienter (3,3 %) med hjernemetastaser CNS-blødning (grad 4 hos alle), når de blev behandlet med bevacizumab, i forhold til 1 tilfælde (grad 5) ud af 96 patienter (1 %), som ikke fik bevacizumab.
In an exploratory retrospective analysis of data from 13 completed randomised trials in patients with various tumour types, 3 patients out of 91 (3.3%) with brain metastases experienced CNS bleeding (all Grade 4) when treated with bevacizumab, compared to 1 case (Grade 5) out of 96 patients (1%) that were not exposed to bevacizumab.
I alt blev 673 patienter randomiseret ligeligt mellem to følgende behandlingsarme:
A total of 673 patients were randomized in equal proportions to the following two treatment arms:
I et klinisk studie er der blevet set en øget hyppighed af CHF hos patienter med diffust storcellet Bcelle lymfom, der fik bevacizumab sammen med en kumulativ doxorubicindosis, som var større end 300 mg/m2.
An increased incidence of CHF has been observed in a clinical trial of patients with diffuse large Bcell lymphoma when receiving bevacizumab with a cumulative doxorubicin dose greater than 300 mg/m2.
I et studie med patienter med platinresistent recidiverende ovariecancer blev der også rapporteret alopeci, slimhindeinflammation, perifer sensorisk neuropati, proteinuri og hypertension, og forekomsten var mindst 5 % højere i kemoterapi + bevacizumab-armen hos patienter ≥ 65 år, som fik bevacizumab, sammenlignet med patienter < 65 år, som fik bevacizumab.
In a study of platinum-resistant recurrent ovarian cancer patients, alopecia, mucosal inflammation, peripheral sensory neuropathy, proteinuria and hypertension were also reported and occurred at a rate at least 5% higher in the CT + BV arm for bevacizumab-treated patients ≥ 65 years of age compared with bevacizumab-treated patients aged < 65 years.
• Gem indlægssedlen.
● Keep this leaflet.
Der blev randomiseret 813 patienter til behandling med IFL + placebo (arm 1) eller IFL + Avastin (5 mg/kg hver 2. uge, arm 2).
Eight hundred and thirteen patients were randomised to receive IFL + placebo (Arm 1) or IFL + Avastin (5 mg/kg every 2 weeks, Arm 2).
• Paclitaxel 80 mg/m2 som 1-times i.v.-infusion på dag 1, 8, 15 og 22 hver 4. uge.
• Paclitaxel 80 mg/m2 as a 1-hour IV infusion on Days 1, 8, 15, and 22 every 4 weeks.
De eksploratoriske PFS- og OS-analyser af kemoterapi-kohorten (paclitaxel, topotecan og pegyleret liposomal doxorubicin) vises i tabel 24.
The exploratory PFS and OS analyses by chemotherapy cohort (paclitaxel, topotecan and PLD) are summarized in Table 24.
Sekundære endepunkter inkluderede progressionsfri overlevelse og objektiv responsrate.
Secondary efficacy endpoints included progression-free survival and objective response rate.
Studiet omfattede ialt 361 patienter, der fik kemoterapi (paclitaxel, topotecan eller pegyleret liposomal doxorubicin) alene eller i kombination med bevacizumab:
A total of 361 patients were enrolled into this study and administered either chemotherapy (paclitaxel, topotecan, or pegylated liposomal doxorubicin (PLD) alone or in combination with bevacizumab:
• Topotecan 4 mg/m2 som 30-minutters i.v.-infusion på dag 1, 8 og 15 hver 4. uge.
• Topotecan 4 mg/m2 as a 30-minute IV infusion on Days 1, 8, and 15 every 4 weeks.
Yderligere tre studier med bevacizumab er blevet udført hos patienter med metastatisk kolorektalkræft: 1.-linje-behandling (NO16966), 2. linje-behandling uden tidligere bevacizumabbehandling (E3200) samt 2. linje-behandling efter sygdomsprogression efter i 1.-linje-behandling med bevacizumab (ML18147).
Three additional studies with bevacizumab have been conducted in mCRC patients: first-line (NO16966), second-line with no previous bevacizumab treatment (E3200), and second-line with previous bevacizumab treatment following disease progression in first-line (ML18147).
1.-linjebehandling af ikke-planocellulær NSCLC i kombination med platinbaseret kemoterapi
First-line treatment of non-squamous NSCLC in combination with platinum-based chemotherapy
For yderligere information henvises til Tabel 3 'Bivirkninger rapporteret post-marketing'.
For further information please refer to Table 3 'Adverse reactions reported in post-marketing setting.'
Når det anvendes til patienter med brystkræft, vil det blive givet sammen med et cytostatikum (lægemiddel mod kræft), der hedder paclitaxel eller capecitabin.
When used for patients with breast cancer, it will be administered with a chemotherapy medicinal product called paclitaxel or capecitabine.
4.8) Der har været sjældne tilfælde af Avastinbehandlede patienter, som har udviklet symptomer, der stemmer overens med PRES, en sjælden neurologisk forstyrrelse, som kan optræde med blandt andre følgende tegn og symptomer: Kramper, hovedpine, forandret mental status, visuelle forstyrrelser eller kortikal blindhed, med eller uden tilknyttet hypertension.
Posterior Reversible Encephalopathy Syndrome (PRES) (see section 4.8) There have been rare reports of Avastin-treated patients developing signs and symptoms that are consistent with PRES, a rare neurologic disorder, which can present with the following signs and symptoms among others: seizures, headache, altered mental status, visual disturbance, or cortical blindness, with or without associated hypertension.
Proteinurien varierede i sværhed fra klinisk symptomfri, forbigående, spor af protein i urinen til nefrotisk syndrom, dog med størstedelen som grad 1 proteinuri (NCI-CTCAE v. 3).
Proteinuria ranged in severity from clinically asymptomatic, transient, trace proteinuria to nephrotic syndrome, with the great majority as Grade 1 proteinuria (NCI-CTCAE v.3).
1.-linjebehandling af ikke-planocellulær NSCLC med EGFR aktiverende mutationer i kombination med erlotinib
First-line treatment of non-squamous NSCLC with EGFR activating mutations in combination with erlotinib
Dette var et fase III, randomiseret, dobbeltblindet studie, der blev udført for at undersøge effekt og sikkerhed ved Avastin i kombination med interferon (IFN) alfa-2a vs IFN alfa-2a alene som 1.linjebehandling af mRCC.
This was a phase III randomised double-blind trial conducted to evaluate the efficacy and safety of Avastin in combination with interferon (IFN) alfa-2a versus IFN alfa-2a alone as first-line treatment in mRCC.
Bedste objektive respons (primær analyse)6 Respondenter (responsrate)2
Best Overall Response - Primary analysis6
Diuretika bør ikke anvendes til behandling af hypertension hos patienter, som får cisplatinbaseret kemoterapi.
The use of diuretics to manage hypertension is not advised in patients who receive a cisplatin-based chemotherapy regimen.
Antal patienter Samlet overlevelse Median (måneder)
Number of Patients Overall Survival Median (months)
På tværs af alle kliniske studier er der set slimhindeblødninger hos op til 50 % af patienterne, som fik Avastin.
Across all clinical trials, mucocutaneous haemorrhage has been seen in up to 50% of Avastin-treated patients.
Rektovaginale fistler er de hyppigste fistler i kategorien gastrointestinale-vaginale fistler.
Recto-vaginal fistulae are the most common fistulae in the GI-vaginal fistula category.
Gastrointestinalt ulcusa
Gastrointestinal ulcera
Overfølsomhedsreaktioner og infusionsreaktioner (ikke kendt) med følgende mulige co-manifestationer: Dyspnø/vejrtrækningsbesvær, blussen/rødme/udslæt, hypotension eller hypertension, nedsat iltmætning, brystsmerter, rigor og kvalme/opkastning (se også pkt.
Hypersensitivity reactions and infusion reactions (not known); with the following possible co-manifestations: dyspnoea/difficulty breathing, flushing/redness/rash, hypotension or hypertension, oxygen desaturation, chest pain, rigors and nausea/vomiting (see also section 4.4 and Hypersensitivity reactions/infusion reactions above)
Bevacizumabs effekt på farmakokinetikken af andre antineoplastiske lægemidlerDer er ikke observeret klinisk relevante interaktioner af bevacizumab på farmakokinetikken af samtidig administreret interferon alfa 2a, erlotinib (og den aktive metabolit OSI-420) eller af følgende kemoterapeutika: irinotecan (og den aktive metabolit SN38), capecitabin, oxaliplatin (bestemt ved måling af frit og totalt platin) og cisplatin.
Effect of bevacizumab on the pharmacokinetics of other antineoplastic agents No clinically relevant interaction of bevacizumab was observed on the pharmacokinetics of coadministered interferon alpha 2a, erlotinib (and its active metabolite OSI-420), or the chemotherapies irinotecan (and its active metabolite SN38), capecitabine, oxaliplatin (as determined by measurement of free and total platinum), and cisplatin.
Disse resultater påviser robusthed af PFS-analysen vist i tabel 16.
These results demonstrate robustness of the analysis of PFS as shown in Table 16.
Overfølsomhed Infusionsreaktionera,b,d
Hypersensitivity, infusion reactionsa,b,d
Studiet inkluderede patienter med epitelial ovariecancer, tubacancer eller primær peritonealcancer, der var progredieret < 6 måneder efter seneste platinbehandling, som bestod som minimum af 4 platinbehandlingsserier.
Eligible patients had epithelial ovarian, fallopian tube or primary peritoneal cancer that progressed within <6 months of previous platinum therapy consisting of a minimum of 4 platinum therapy cycles.
• sår i munden og spiserøret, som kan være smertefulde og forårsage synkeproblemer,
• sores in the mouth and the tube from the mouth to the stomach, which may be painful and cause difficulty swallowing,
Meget almindelige bivirkninger (påvirker flere end 1 patient ud af 10), som ikke var alvorlige, omfatter:
Very common (affects more than 1 user in 10) side effects, which were not severe, include:
Cisplatin/Gemcitabin + placebo
Cisplatin/Gemcitabine + placebo
Valg af kemoterapi omfattede capecitabin, taxan (proteinbundet paclitaxel, docetaxel) og antracyklinbaserede stoffer (doxorubicin/ cyclophosphamid, epirubicin/cyclophosphamid, 5-fluoruracil/doxorubicin/cyclophosphamid, 5fluoruracil/epirubicin/cyclophosphamid) administreret hver 3. uge.
The choices of chemotherapy included capecitabine, taxane (protein-bound paclitaxel, docetaxel), and anthracycline-based agents (doxorubicin/ cyclophosphamide, epirubicin/ cyclophosphamide, 5-fluorouracil/ doxorubicin/ cyclophosphamide, 5-fluorouracil/epirubicin/cyclophosphamide) given every three weeks (q3w).
I nogle af disse tilfælde var intraabdominal inflammation allerede erkendt, enten fra mavesår, tumornekrose, divertikulitis eller kemoterapiassocieret colitis.
In some cases underlying intra-abdominal inflammation was present, either from gastric ulcer disease, tumour necrosis, diverticulitis, or chemotherapy-associated colitis.
Intestinal perforation Ileus Intestinal obstruktion Rektovaginal e fistlerd,e
Intestinal perforation, Ileus, Intestinal obstruction, Recto-vaginal fistulaed,e,
• Avastin kan øge risikoen for at få protein i urinen, især hvis du har forhøjet blodtryk.
● This medicine increases the risk of having protein in your urine especially if you already have high blood pressure.
Studiet evaluerede effekten af at tilføje Avastin til carboplatin+paclitaxel og fortsætte med Avastin som monoterapi til sygdomsprogession eller uacceptabel toksicitet, sammenlignet med carboplatin+paclitaxel alene.
The study evaluated the effect of adding Avastin to carboplatin+paclitaxel and continuing Avastin as a single agent until disease progression or unacceptable toxicity compared to carboplatin+paclitaxel alone.
Tabel 9.
Table 9
Hazard ratio (95 % konfidensinterval) > 12 måneder (n=282) Median
Hazard ratio (95% CI) > 12 months (n=282) Median
Nogle patienter kan derudover lide af hypertension (inklusive hypertensive kriser), forhøjet kreatinin og neurologiske symptomer.
In addition, hypertension (including hypertensive crisis), elevated creatinine, and neurological symptoms were observed in some of these patients.
Medianalderen var 60 år i CP-armen og 59 år i CPB-armen.
60.0 years in the CP arm and 59.0 years in the CPB arm.
• forhøjet blodtryk.
• high blood pressure.
Overfølsømhed Infusionsreaktioner a,b,c
Hypersensitivity, infusion reactions a,b,c
Avastin vs ingen Avastin
Avastin vs. No Avastin
I forhold til kontrolarmen.
Relative to the control arm.
Hos patienter i studie AVF3694g, som fik antracykliner samtidig med bevacizumab, svarede hyppigheden af CHF af grad 3 eller højere i de respektive bevacizumab- og kontrolarme til de hyppigheder, som er set i andre studier af metastatisk brystkræft: 2,9 % i antracyklin + bevacizumab-armen og 0 % i antracyklin + placebo-armen.
For patients in study AVF3694g who received anthracyclines concomitantly with bevacizumab, the incidences of Grade 3 or higher CHF for the respective bevacizumab and control arms were similar to those in the other studies in metastatic breast cancer: 2.9% in the anthracycline + bevacizumab arm and 0% in the anthracycline + placebo arm.
Det anbefales, at behandlingen fortsættes indtil progression af den underliggende sygdom eller indtil uacceptabel toksicitet.
It is recommended that treatment be continued until progression of the underlying disease or until unacceptable toxicity.
Sjælden Meget sjælden
Uncommon Rare Very Rare
Resultaterne for PFS af de individuelle kemoterapeutika inkluderet i indikationen er opsummeret nedenfor:
Summarised below are PFS results for the individual chemotherapy agents included in the indication:
DATO FOR ÆNDRING AF TEKSTEN Yderligere oplysninger om Avastin findes på Det Europæiske Lægemiddelagenturs hjemmeside http://www.ema.europa.eu/.
Detailed information on this medicinal product is available on the website of the European Medicines Agency (EMA): http://www.ema.europa.eu
Hos de patienter, der blev behandlet med Avastin, er der fra kliniske studier set en stigning på mindst 2 % i hyppigheden af følgende grad 3 og 4 (NCI-CTCAE v. 3) laboratorieanormaliteter sammenlignet med kontrolgrupperne: Hyperglykæmi, nedsat hæmoglobin, hypokaliæmi, hyponatriæmi, nedsat antal hvide blodceller, stigning i international normaliseret ratio (INR).
Across clinical trials, the following Grade 3 and 4 (NCI-CTCAE v.3) laboratory abnormalities occurred in patients treated with Avastin with at least a 2% difference compared to the corresponding control groups: hyperglycaemia, decreased haemoglobin, hypokalaemia, hyponatraemia, decreased white blood cell count, increased international normalised ratio (INR).
Objektiv responsrate Rate
Objective response rate Rate
Patienter med nedsat leverfunktion: Sikkerheden og effekten er ikke undersøgt hos patienter med nedsat leverfunktion (se pkt.
Patients with renal impairment: The safety and efficacy have not been studied in patients with renal impairment (see section 5.2).
Responsvarighed Median tid (måneder)
Duration of response Median time (months)
29 % af patienterne i CPP- og CPB15-armene og 26 % i CPB15+-armen var over 65 år.
60 years in CPP and CPB15 arms and 59 years in CPB15+ arm; and 29% of patients in CPP or CPB15 and 26% in CPB15+ were over 65 years of age.
• forhøjet blodtryk,
• high blood pressure,
Sammenlagt blev 1.528 patienter randomiseret til to lige store arme:
A total of 1528 patients were randomised in equal proportions to the following two arms:
Posteriort reversibelt encefalopati-syndrom (PRES) (sjælden) (se også pkt.
Posterior Reversible Encephalopathy Syndrome (PRES), (rare) (see also section 4.4)
IRC-vurdering
IRC Assessment
Dyb vene trombose
Deep vein thrombosis
● I et enkelt-arms-studie (PBTC-022) blev18 børn med recidiverende eller progredierende højgrads-gliom, som ikke involverede hjernebroen (herunder 8 med glioblastom [WHO grad IV], 9 med anaplastisk astrocytom [grad III] og 1 med anaplastisk oligodendrogliom [grad III]), behandlet med bevacizumab (10 mg/kg) med 2 ugers mellemrum og derefter med bevacizumab i kombination med CPT-11 (125-350 mg/m²) hver anden uge indtil progression.
• In a single-arm study (PBTC-022), 18 children with recurrent or progressive non-pontine high-grade glioma (including 8 with glioblastoma [WHO Grade IV], 9 with anaplastic astrocytoma [Grade III] and 1 with anaplastic oligodendroglioma [Grade III]) were treated with bevacizumab (10 mg/kg) two weeks apart and then with bevacizumab in combination with CPT-11 (125-350 mg/m²) once every two weeks until progression.
Alvorlige bivirkninger, som kan være meget almindelige (påvirker flere end 1 patient ud af 10), omfatter:
Severe side effects, which may be very common (affects more than 1 user in 10), include:
(p-værdi 0,3360)
(p-value 0.3360)
Patienterne blev randomiseret til paclitaxel alene (90 mg/m2 indgivet intravenøst som 1-times infusion en gang ugentligt i tre ud af fire uger) eller i kombination med Avastin (10 mg/kg indgivet som intravenøs infusion hver 2. uge).
Patients were randomised to paclitaxel alone (90 mg/m2 IV over 1 hour once weekly for three out of four weeks) or in combination with Avastin (10 mg/kg IV infusion every two weeks).