natgillin/translations-raw huggingface dataset:
Det anbefales kraftigt, at Erbitux kun gives under graviditet eller til kvinder, som benytter adækvat prævention, hvis den potentielle fordel retfærdiggør en potentiel risiko for fostret.
It is strongly recommended that Erbitux be given during pregnancy or to any woman not employing adequate contraception only if the potential benefit justifies a potential risk to the foetus.
Kvinder frarådes at amme under behandling med Erbitux og i 2 måneder efter sidste dosis, da det ikke vides, om cetuximab udskilles i modermælk.
5 It is recommended that women do not breast-feed during treatment with Erbitux and for 2 months after the last dose, because it is not known whether cetuximab is excreted in breast milk.
5 4. 7 Virkning på evnen til at føre motorkøretøj eller betjene maskiner
4.7 Effects on ability to drive and use machines
Hvis patienter får behandlingsrelaterede symptomer, som påvirker deres koncentrations - og reaktionsevne, frarådes det, at de fører motorkøretøj eller betjener maskiner, før effekten tager af.
If patients experience treatment-related symptoms affecting their ability to concentrate and react, it is recommended that they do not drive or use machines until the effect subsides.
De primære bivirkninger af cetuximab er hudreaktioner, som forekommer hos mere end 80% af patienterne, hypomagnesæmi, som forekommer hos mere end 10% af patienterne og infusionsrelaterede reaktioner, som forekommer med milde eller moderate symptomer hos mere end 10% af patienterne og med svære symptomer hos mere end 1% af patienterne.
The primary undesirable effects of cetuximab are skin reactions, which occur in more than 80% of patients, hypomagnesaemia which occurs in more than 10% of patients and infusion-related reactions, which occur with mild to moderate symptoms in more than 10% of patients and with severe symptoms in more than 1% of patients.
Følgende definitioner gælder for den hyppighedsterminologi, som anvendes herefter:
The following definitions apply to the frequency terminology used hereafter:
Meget almindelig (≥ 1/ 10) Almindelig (≥ 1/ 100, < 1/ 10) Ikke almindelig (≥ 1/ 1. 000, < 1/ 100) Sjælden (≥ 1/ 10. 000, < 1/ 1. 000) Meget sjælden (< 1/ 10. 000) Hyppighed kendes ikke (kan ikke estimeres ud fra de data, der er til rådighed)
Very common (≥ 1/ 10) Common (≥ 1/ 100 to < 1/ 10) Uncommon (≥ 1/ 1,000 to < 1/ 100) Rare (≥ 1/ 10,000 to < 1/ 1,000) Very rare (< 1/ 10,000) Frequency not known (cannot be estimated from the available data)
Konjunctivitis.
Conjunctivitis.
Blefaritis, keratitis.
Blepharitis, keratitis.
Lundeemboli.
Pulmonary embolism.
Diaré, kvalme, opkast.
Diarrhoea, nausea, vomiting.
Hyppighed kendes ikke:
Very common:
Hudreaktioner *.
Skin reactions*.
Superinfektion af hudlæsioner *.
Superinfection of skin lesions*.
6 Metabolisme og ernæring
6 Metabolism and nutrition disorders
4. 4).
Hypomagnesaemia (see section 4.4).
4. 4); anorexi som kan føre til vægttab.
Dehydration, in particular secondary to diarrhoea or mucositis; hypocalcaemia (see section 4.4); anorexia which may lead to weight decrease.
Milde eller moderate infusionsrelaterede reaktioner *, mild til moderat mucositis, som kan føre til næseblod.
Mild or moderate infusion-related reactions*; mild to moderate mucositis which may lead to epistaxis.
Svære infusionsrelaterede reaktioner *, træthed.
Severe infusion-related reactions*, fatigue.
Disse omfatter symptomer som feber, kulderystelser, svimmelhed eller dyspnø og forekommer i tidsmæssig tæt tilknytning til især den første infusion med cetuximab.
Mild or moderate infusion-related reactions are very common comprising symptoms such as fever, chills, dizziness, or dyspnoea that occur in a close temporal relationship mainly to the first cetuximab infusion.
Der kan ofte forekomme svære infusionsrelaterede reaktioner, i sjældne tilfælde med dødelig udgang.
Severe infusion-related reactions may commonly occur, in rare cases with fatal outcome.
De udvikler sig som regel under eller inden for 1 time efter den indledende infusion, men kan også forekomme efter adskillige timer eller i forbindelse med efterfølgende infusioner.
They usually develop during or within 1 hour of the initial cetuximab infusion, but may occur after several hours or with subsequent infusions.
Selvom den underliggende mekanisme ikke er identificeret, kan nogle af disse reaktioner være anafylaktoide/ anafylaktiske af natur, og kan omfatte symptomer som bronkospasme, urticaria, hypotension, bevidstløshed eller chok.
Although the underlying mechanism has not been identified, some of these reactions may be anaphylactoid/ anaphylactic in nature and may include symptoms such as bronchospasm, urticaria, hypotension, loss of consciousness or shock.
I sjældne er der blevet observeret tilfælde af angina pectoris, myokardieinfarkt eller hjertestop.
In rare cases, angina pectoris, myocardial infarction or cardiac arrest have been observed.
4. 4.
For clinical management of infusion-related reactions, see section 4.4.
Reaktionerne ses hovedsageligt som akne- lignende udslæt og/ eller mindre hyppigt som pruritus, tør hud, afskalning, hypertrichose eller neglelidelser (f. eks. paronychia).
Skin reactions may develop in more than 80% of patients and mainly present as acne-like rash and/ or, less frequently, as pruritus, dry skin, desquamation, hypertrichosis, or nail disorders (e. g. paronychia).
4. 4), heler hudreaktionerne generelt uden mén efter nogen tid, når behandlingen ophører.
They generally resolve, without sequelae, over time following cessation of treatment if the recommended adjustments in dose regimen are followed (see section 4.4).
Ifølge NCI- CTC er grad 2- hudreaktioner karakteriseret ved udslæt på op til 50% af legemsoverfladen, mens grad 3- reaktioner påvirker 50% eller mere af legemsoverfladen.
According to NCI-CTC, grade 2 skin reactions are characterised by rash up to 50% of body surface area, while grade 3 reactions affect equal or more than 50% of body surface area.
Dette kan medføre efterfølgende komplikationer, f. eks. cellulitis, erysipelas eller, potentielt med dødeligt udfald, staphylococcal scalded skin syndrome (SSSS) eller sepsis.
7 Skin lesions induced by cetuximab may predispose patients to superinfections (e. g. with S. aureus), which may lead to subsequent complications, e. g. cellulitis, erysipelas, or, potentially with fatal outcome, staphylococcal scalded skin syndrome or sepsis.
I kombination med lokal strålebehandling af hoved - og halsområdet var de yderligere bivirkninger dem, som er typiske for strålebehandling (f. eks. mucositis, stråledermatit, dysfagi eller leukopeni, der hovedsageligt optrådte som lymfocytopeni).
In combination with local radiation therapy of the head and neck area, additional undesirable effects were those typical of radiation therapy (such as mucositis, radiation dermatitis, dysphagia or leukopenia, mainly presenting as lymphocytopenia).
I et randomiseret, kontrolleret, klinisk forsøg med 424 patienter var antallet af svær, akut stråledermatit og mucositis samt af sene rapporterede hændelser, relaterede til strålebehandlingen, let forhøjet hos patienter, som fik strålebehandling i kombination med cetuximab, sammenlignet med dem, som kun fik strålebehandling.
In a randomised controlled clinical study with 424 patients, reporting rates of severe acute radiation dermatitis and mucositis as well as of late radiation-therapy-related events were slightly higher in patients receiving radiation therapy in combination with cetuximab than in those receiving radiation therapy alone.
Der er begrænsede erfaringer med enkeltdoser højere end 400 mg/ m² legemsoverflade eller ugentlige administrationer af doser på mere end 250 mg/ m² legemsoverflade.
There is limited experience with single doses higher than 400 mg/ m² body surface area to date or weekly administrations of doses higher than 250 mg/ m² body surface area.
4. 8.
In clinical studies with doses up to 700 mg/ m² given every 2 weeks the safety profile was consistent with that described in section 4.8.
Antineoplastiske stoffer, monoklonale antistoffer, ATC- kode:
Antineoplastic agents, monoclonal antibodies, ATC code:
Cetuximab er et kimerisk monoklonalt IgG1- antistof specifikt rettet mod den epidermale vækstfaktorreceptor (EGFR).
Cetuximab is a chimeric monoclonal IgG1 antibody that is specifically directed against the epidermal growth factor receptor (EGFR).
EGFR- signalbaner er involverede i kontrollen af cellernes overlevelse, udvikling i cellecyklus, angiogenese, cellemigration og celleinfiltration/ metastaser.
EGFR signalling pathways are involved in the control of cell survival, cell cycle progression, angiogenesis, cell migration and cellular invasion/ metastasis.
Cetuximab binder sig til EGFR med en affinitet, som er cirka 5 til 10 gange højre end kroppens egne ligander.
Cetuximab binds to the EGFR with an affinity that is approximately 5- to 10fold higher than that of endogenous ligands.
Cetuximab blokerer bindingen af kropsegne EGFR- ligander, hvilket hæmmer receptorens funktion.
Cetuximab blocks binding of endogenous EGFR ligands resulting in inhibition of the function of the receptor.
Det forårsager yderligere optagelse af EGFR i cellerne, hvilket kan medføre ned- regulering af EGFR.
It further induces the internalisation of EGFR, which can lead to down-regulation of EGFR.
Cetuximab påvirker også cytotoksiske immun- effektorceller mod tumorceller med EGFR (antibody dependent cell- mediated cytotoxicity, ADCC).
Cetuximab also targets cytotoxic immune effector cells towards EGFR-expressing tumour cells (antibody dependent cell-mediated cytotoxicity, ADCC).
8 Cetuximab binder sig ikke til andre receptorer i HER- familien.
8 Cetuximab does not bind to other receptors belonging to the HER family.
Proteinproduktet af proto- oncogenet KRAS (Kirsten rat sarcoma 2 viral oncogene homologue) er en central, downstream signaltransducer for EGFR.
The protein product of the proto-oncogene KRAS (Kirsten rat sarcoma 2 viral oncogene homologue) is a central down-stream signal-transducer of EGFR.
I tumorer bidrager aktivering af KRAS via EGFR til EGFR- medieret øget celleproliferation, celleoverlevelse og produktion af pro- angiogene faktorer.
In tumours, activation of KRAS by EGFR contributes to EGFR-mediated increased proliferation, survival and the production of pro-angiogenic factors.
KRAS er en af de hyppigst aktiverede oncogener ved human cancer.
KRAS is one of the most frequently activated oncogenes in human cancers.
Mutationer af KRAS- genet ved visse hotspots (primært codon 12 og 13) resulterer i konstitutiv aktivering af KRAS- proteinet uafhængigt af EGFR- signalering.
Mutations of the KRAS gene at certain hot-spots (mainly codons 12 and 13) result in constitutive activation of the KRAS protein independently of EGFR signalling.
I såvel in vitro - som in vivo- analyser hæmmer cetuximab formeringen og fremkalder apoptose hos humane tumorceller med EGFR.
In both in vitro and in vivo assays, cetuximab inhibits the proliferation and induces apoptosis of human tumour cells that express EGFR.
In vivo hæmmer cetuximab tumorcellers angiogene faktorer og fremkalder en reduktion i tumorens neo- vaskularisering og metastasering.
In vivo cetuximab inhibits expression of angiogenic factors by tumour cells and causes a reduction in tumour neo-vascularisation and metastasis.
Udviklingen af humane anti- kimeriske antistoffer (human anti- chimeric antibodies, HACA) er en effekt i klassen af monoklonale, kimeriske antistoffer.
The development of human anti-chimeric antibodies (HACA) is a class effect of monoclonal chimeric antibodies.
Generelt blev der set målbare HACA- titrer hos 3, 4% af de undersøgte patienter med incidenser i intervallet fra 0% til 9, 6% i forsøgene med målindikationer.
Overall, measurable HACA titres were noted in 3.4% of the patients studied, with incidences ranging from 0% to 9.6% in the target indication studies.
Colorectal- cancer
Colorectal cancer
En tumor blev betragtet som EGFR- positiv, hvis der kunne identificeres en enkelt, farvet celle.
A tumour was considered to be EGFR-expressing, if one stained cell could be identified.
Cirka 75% af patienterne med metastatisk colorectal- cancer, som blev screenet til kliniske forsøg, havde en tumor med EGFR og blev derfor betragtet som egnede til behandling med cetuximab.
Approximately 75% of the patients with metastatic colorectal cancer screened for clinical studies had an EGFR-expressing tumour and were therefore considered eligible for cetuximab treatment.
Ved metastatisk colorectal cancer ligger incidensen af KRAS- mutationer i området 30 - 50%.
In metastatic colorectal cancer, the incidence of KRAS mutations is in the range of 30 - 50%.
Nye data viser, at patienter med metatastisk colorectal cancer af KRAS- vildtypen har en signifikant højere chance for at få gavn af behandling med cetuximab eller en kombination af cetuximab og kemoterapi.
Recent data demonstrate that patients with KRAS wild-type metastatic colorectal cancer have a significantly higher chance to benefit from treatment with cetuximab or a combination of cetuximab and chemotherapy.
Cetuximab som enkeltstofbehandling eller i kombination med kemoterapi blev undersøgt i 5 randomiserede, kontrollerede, kliniske forsøg og flere understøttende forsøg.
Cetuximab as a single agent or in combination with chemotherapy was investigated in 5 randomised controlled clinical studies and several supportive studies.
De 5 randomiserede forsøg undersøgte i alt 3. 734 patienter med metastatisk colorectal- cancer, og påvist EGFR med en ECOG- performance status på ≤ 2.
The 5 randomised studies investigated a total of 3734 patients with metastatic colorectal cancer, in whom EGFR expression was detectable and who had an ECOG performance status of ≤ 2.
Størstedelen af de inkluderede patienter havde en ECOG- performance status på ≤ 1.
The majority of patients included had an ECOG performance status of ≤ 1.
Cetuximab blev i alle forsøg administreret som beskrevet i afsnit 4. 2.
In all studies, cetuximab was administered as described in section 4.2.
KRAS- status blev anerkendt som prædiktiv faktor for behandlingen med cetuximab i 4 af de randomiserede, kontrollerede forsøg.
The KRAS status was recognised as predictive factor for the treatment with cetuximab in 4 of the randomised controlled studies.
KRAS- mutationsstatus var tilgængelig for 1. 261 patienter.
KRAS mutational status was available for 1261 patients.
Kun i forsøg EMR 62 202- 007 var det ikke muligt at foretage en analyse.
Only in study EMR 62 202-007, an analysis was not possible.
9 Cetuximab i kombination med kemoterapi
9 Cetuximab in combination with chemotherapy
Dette randomiserede forsøg med patienter med metastatisk colorectal- cancer, som ikke tidligere havde fået behandling for metastatisk sygdom, sammenlignede kombinationen af cetuximab og irinotecan plus 5- fluorouracil/ folinsyre- infusion (5- FU/ FA) (599 patienter) med den samme kemoterapibehandling uden cetuximab (599 patienter).
This randomised study in patients with metastatic colorectal cancer who had not received prior treatment for metastatic disease compared the combination of cetuximab and irinotecan plus infusional 5-fluorouracil/ folinic acid (5-FU/ FA) (599 patients) to the same chemotherapy alone (599 patients).
KRAS- status, var 64%.
The proportion of patients with KRAS wild-type tumours from the patient population evaluable for KRAS status comprised 64%.
Forsøgets effektdata er resumeret i nedenstående tabel:
The efficacy data generated in this study are summarised in the table below:
Population med KRAS- vildtypen
KRAS wild-type population
Variabel/ statistisk
Variable/ statistic
FOLFIRI Cetux
FOLFIRI Cetuxi
Cetuximab FOLFIRI Cetuximab
Cetuximab FOLFIRI Cetuximab
plus FOLFIRI
plus FOLFIRI
ORR
ORR
(N=599) (N=599)
(N=599) (N=599)
% (95% CI) p- værdi PFS
% (95% CI) p-value PFS
Risikorate (95% CI) p- værdi
Hazard Ratio (95% CI) p-value
CI = confidence interval, konfidensinterval, FOLFIRI irinotecan plus 5- FU/ FA- infusion, ORR = objective response rate (patienter med komplet respons eller delvis respons), PFS = progression- free survival time
CI = confidence interval, FOLFIRI = irinotecan plus infusional 5-FU/ FA, ORR = objective response rate (patients with complete response or partial response), PFS = progression-free survival time
Dette randomiserede forsøg med patienter med metastatisk colorectal cancer, som ikke tidligere havde fået behandling for metastatisk sygdom, sammenlignede kombinationen af cetuximab og oxaliplatin plus 5- fluorouracil / folinsyre- infusion (5- FU/ FA) (169 patienter) med den samme kemoterapibehandling uden cetuximab (168 patienter).
This randomised study in patients with metastatic colorectal cancer who had not received prior treatment for metastatic disease compared the combination of cetuximab and oxaliplatin plus infusional 5-fluorouracil/ folinic acid (5-FU/ FA) (169 patients) to the same chemotherapy alone (168 patients).
KRAS- status, var 58%.
The proportion of patients with KRAS wild-type tumours from the patient population evaluable for KRAS status comprised 58%.
FOLFOX Cetu
FOLFOX Cetux
Cetuximab FOLFOX Cetuximab
Cetuximab FOLFOX Cetuximab
plus FOLFOX
plus FOLFOX
CI = confidence interval, konfidensinterval, FOLFOX = oxaliplatin plus 5- FU/ FA- infusion, ORR = objective response rate (patienter med komplet respons eller delvis respons), PFS = progression- free survival time
CI = confidence interval, FOLFOX = oxaliplatin plus infusional 5-FU/ FA, ORR = objective response rate (patients with complete response or partial response), PFS = progression-free survival time
Dette randomiserede forsøg med patienter med metastatisk colorectal- cancer, som tidligere havde fået behandling med oxaliplatin plus fluoropyrimidin for metastatisk sygdom, sammenlignede kombinationen af cetuximab og irinotecan (648 patienter) med irinotecan alene (650 patienter).
This randomised study in patients with metastatic colorectal cancer who had received initial combination treatment with oxaliplatin plus fluoropyrimidine for metastatic disease compared the combination of cetuximab and irinotecan (648 patients) with irinotecan alone (650 patients).
10 Der fremkom ikke nogen signifikant forskel med hensyn til den samlede overlevelsestid i dette forsøg.
10 A significant difference in overall survival time could not be shown in this study.
Efter sygdomsprogression, blev der hos 50% af patienterne i den behandlingsarm, der kun fik irinotecan, indledt en behandling med midler rettet imod EGFR, hvilket sandsynligvis havde betydning for overlevelsesresultaterne.
Following disease progression, treatment with EGFR-targeting agents was initiated in 50% of patients in the irinotecan-alone arm, which most likely impacted survival results.
Den objektive responsrate og progressionsfri overlevelsestid blev signifikant forbedret med cetuximab.
Objective response rate and progression free survival time were significantly improved with cetuximab.
Disse resultater skal imidlertid fortolkes med forsigtighed, da der ikke er blevet foretaget en uafhængig kontrol af billeddata.
However, as no independent review of imaging data was conducted, these results have to be interpreted with caution.
Dette randomiserede forsøg med patienter med metastatisk colorectal- cancer, som havde fået virkningsløs, irinotecan- baseret behandling for metastatisk sygdom som sidste behandling inden tilmelding til forsøget, sammenlignede kombinationen af cetuximab og irinotecan (218 patienter) med cetuximab- monoterapi (111 patienter).
This randomised study in patients with metastatic colorectal cancer after failure of irinotecan-based treatment for metastatic disease as the last treatment before study entry compared the combination of cetuximab and irinotecan (218 patients) with cetuximab monotherapy (111 patients).
Kombinationen af cetuximab med irinotecan sammenlignet med cetuximab- monoterapi reducerede den samlede risiko for sygdomsudvikling med 46% og øgede den objektive responsrate væsentligt.
The combination of cetuximab with irinotecan compared to cetuximab alone reduced the overall risk of disease progression by 46% and significantly increased objective response rate.
I opfølgningsbehandlingen fik dog næsten 50% af patienterne fra armen med cetuximab- monoterapi en kombination af cetuximab og irinotecan efter progression af sygdommen, hvilket kan have påvirket den samlede overlevelsestid.
In the randomised trial, the improvement in overall survival time did not reach statistical significance; however, in the follow-up treatment, nearly 50% of the patients of the cetuximab alone arm received a combination of cetuximab and irinotecan after progression of disease, which may have influenced overall survival time.
Dette randomiserede forsøg med patienter med metastatisk colorectal- cancer, som tidligere havde fået behandling med oxaliplatin, irinotecan plus fluoropyrimidin for metastatisk sygdom, sammenlignede kombinationen af cetuximab som enkeltstof sammen med "bedste understøttende pleje" ("best supportive care", BSC) (287 patienter) med "bedste understøttende pleje" alene (285 patienter).
This randomised study in patients with metastatic colorectal cancer who had received prior oxaliplatin-, irinotecan- and fluoropyrimidine-based treatment for metastatic disease compared the addition of cetuximab as a single agent to best supportive care (BSC) (287 patients) with best supportive care (285 patients).
Andelen af patienter i patientpopulationen med tumorer af KRAS- vildtypen, som kunne vurderes med hensyn til KRAS- status, var 59%.
The proportion of patients with KRAS wild-type tumours from the patient population evaluable for KRAS status comprised 59%.
Tilføjelse af cetuximab til "bedste understøttende pleje" reducerede den samlede risiko for dødsfald i den samlede forsøgspopulation med 23% og den samlede risiko for sygdomsudvikling med 32%.
Addition of cetuximab to best supportive care reduced the overall risk of death in the overall study population by 23% and the overall risk of disease progression by 32%.
Foreløbige data fra patienter med tumorer af KRAS- vildtypen viste en mere udtalt, fordelagtig virkning af cetuximab både på den samlede og den progressionsfrie overlevelsestid.
Preliminary data from patients with KRAS wild-type tumours showed a more pronounced beneficial effect of cetuximab on overall survival time and progression free survival time.
Der blev ikke foretaget immunohistokemisk påvisning af EGFR, da mere end 90% af patienterne med planocellulært carcinom i hoved og hals havde tumorer, som var EGFR- positive.
Immunohistochemical detection of EGFR expression was not performed since more than 90% of patients with squamous cell cancer of the head and neck have tumours that express EGFR.
Dette randomiserede forsøg sammenlignede kombinationen af cetuximab og strålebehandling (211 patienter) med strålebehandling alene (213 patienter) hos patienter med lokalt fremskreden planocellulært carcinom i hoved og hals.
This randomised study compared the combination of cetuximab and radiation therapy (211 patients) with radiation therapy alone (213 patients) in patients with locally advanced squamous cell cancer of the head and neck.
4. 2, indtil strålebehandlingsperioden blev afsluttet.
Cetuximab was started one week before radiation therapy and administered at the doses described in section 4.2 until the end of the radiation therapy period.
11 Forsøgets effektdata er resumeret i nedenstående tabel:
11 The efficacy data generated in this study are summarised in the table below:
Variabel/ statistik
Variable/ statistic
Strålebehandling plus cetuximab (N=211)
Radiation therapy + cetuximab (N=211)
Strålebehandling alene (N=213)
Radiation therapy alone (N=213)
Locoregional kontrol
Locoregional control
måneder, median (95% CI)
months, median (95% CI)
Risikorate (95% CI) p- værdi OS
Hazard Ratio (95% CI) p-value OS
CI = confidence interval, konfidensinterval, OS = overall survival time, et "+" betyder, at den øvre grænse ikke var nået ved "cut- off"
CI = confidence interval, OS = overall survival time, a '+ 'denotes that the upper bound limit had not been reached at cut-off