natgillin/translations-raw huggingface dataset:
På tidspunktet for den forud specificerede interimanalyse var median-TTP for sunitinib 28,9 uger (95%CI = 21,3 - 34,1) baseret på investigators vurderinger og 27,3 uger (95% CI = 16,0 - 32,1) baseret på Independent Review Board, og den var statistisk signifikant længere end TTP for placebo på 5,1 uger (95% CI = 4,4 - 10,1 uger; p<0,001) baseret på investigators vurderinger og 6,4 uger (95% CI = 4,410,0S) baseret på Independent Review Board.
At the time of the prespecified interim analysis, the median TTP on sunitinib was 28.9 weeks (95% CI: 21.3, 34.1) as assessed by the investigator and 27.3 weeks (95% CI: 16.0, 32.1) as assessed by the independent review and was statistically significantly longer than the TTP on placebo of 5.1 weeks (95% CI: 4.4, 10.1) as assessed by the investigator and 6.4 weeks (95% CI: 4.4, 10.0) as assessed by the independent review.
De hyppigste bivirkninger af alle grader (ses hos patienter i RCC, GIST og pNET registreringsstudier) er appetitløshed, smagsforstyrrelser, hypertension, træthed, gastrointestinale forstyrrelser (dvs. diarré, kvalme, stomatitis, dyspepsi og opkastning), misfarvning af huden og palmoplantar erytrodysæstesi.
The most common adverse reactions of any grade (experienced by patients in RCC, GIST, and pNET registrational trials) included decreased appetite, taste disturbance, hypertension, fatigue, gastrointestinal disorders (i.e. diarrhoea, nausea, stomatitis, dyspepsia, and vomiting), skin discolouration, and palmar-plantar erythrodysaesthesia syndrome.
Fortæl det til lægen, hvis du hurtigt bliver træt, føler dig kuldskær eller hvis din stemme bliver dybere, mens du tager Sutent.
Tell your doctor if you get tired more easily, generally feel colder than other people, or your voice deepens whilst taking Sutent.
26% af de patienter, der fik sunitinib til behandling af cytokin-refraktær mRCC, oplevede blødning.
Of patients receiving sunitinib for cytokine-refractory MRCC, 26% experienced bleeding.
Der er set tilfælde af arterielle tromboemboliske hændelser (ATE), hvoraf nogle var letale, hos patienter behandlet med sunitinib.
Cases of arterial thromboembolic events (ATE), sometimes fatal, have been reported in patients treated with sunitinib.
Endepunkt
Final
Fortæl det til lægen, hvis du føler dig svimmel, eller besvimer eller mærker unormale hjerteslag, mens du tager Sutent.
Tell your doctor if you feel dizzy, faint, or have abnormal heartbeats while taking Sutent.
Gastrointestinal stromal tumor (GIST)
Gastrointestinal stromal tumour (GIST)
Erfaringen med anvendelse af sunitinib hos pædiatriske patienter er begrænset (se pkt.
Experience on the use of sunitinib in paediatric patients is limited (see section 4.2).
Immunsystemet Der er rapporteret tilfælde af overfølsomhedsreaktioner herunder angioødem (se pkt.
Immune system disorders Hypersensitivity reactions, including angioedema, have been reported (see section 4.4).
Hovedparten af disse tilfælde blev set hos patienter med kendte risikofaktorer for osteonekrose af kæben, især behandling med intravenøst bisfosfonat og/eller anamnese med tandproblemer, som krævede invasiv tandbehandling (se også pkt.
Cases of ONJ have been reported in patients treated with Sutent, most of which occurred in patients who had identified risk factors for ONJ, in particular, exposure to intravenous bisphosphonates and/or a history of dental disease requiring invasive dental procedures (see also section 4.4).
Kvinders og mænds prævention
Contraception in males and females
Tilfælde af tumorblødning, til tider forbundet med tumornekrose er rapporteret, nogle af disse blødningstilfælde var letale.
Events of tumour haemorrhage, sometimes associated with tumour necrosis, have been reported; some of these haemorrhagic events were fatal.
Forlængelse af QT-intervallet og Torsades de pointes er set hos patienter, som har fået sunitinib.
Prolongation of QT interval and Torsade de pointes have been observed in sunitinib-exposed patients.
• Tumorlysesyndrom, som er forskellige komplikationer, der kan opstå under behandling af kræft.
• Tumour lysis syndrome (TLS) - TLS consists of a group of metabolic complications that can occur during treatment of cancer.
• Nedsat antal blodplader og røde og hvide blodlegemer.
• Reduction in the number of platelets, red blood cells and/or white blood cells (e.g. neutrophils).
Hos raske forsøgspersoner medførte samtidig administration af en enkeltdosis af sunitinib og den potente CYP3A4-induktor, rifampin, en reduktion i samlet [sunitinib + primær metabolit] Cmax og AUC0- værdi på henholdsvis 23% og 46%.
In healthy volunteers, concomitant administration of a single dose of sunitinib with the CYP3A4 inducer rifampicin resulted in a reduction of the combined [sunitinib + primary metabolite] Cmax and AUC0- values of 23% and 46%, respectively.
Disse skyldes nedbrydning af døende kræftceller og kan omfatte: kvalme, stakåndethed, uregelmæssige hjerteslag (puls), muskelkramper, krampeanfald, grumset urin, træthed kombineret med unormale blodprøveresultater (høje koncentrationer af kalium-, urinsyre- og fosfat i blodet og lav koncentration af kalcium i blodet).
These complications are caused by the break-down products of dying cancer cells and may include the following: nausea, shortness of breath, irregular heartbeat, muscular cramps, seizure, clouding of urine and tiredness associated with abnormal laboratory test results (high potassium, uric acid and phosphorous levels and low calcium levels in the blood) that can lead to changes in kidney function and acute renal failure.
Forkortelser: CI=konfidensinterval; IFN-α=interferon-alfa; ITT=intent-to-treat; N=antal patienter; NA= ikke relevant; OS=samlet overlevelse; PFS= progressions-fri overlevelse.
Abbreviations: CI=confidence interval; INF-α=interferon-alfa; ITT=intent-to-treat; N=number of patients; NA=not applicable; OS=overall survival; PFS=progression-free survival.
• Åndenød.
• Shortness of breath.
63 patienter fik en oral initialdosis på 50 mg sunitinib 1 gang dagligt i 4 på hinanden følgende uger efterfulgt af 2 ugers pause for at fuldføre en fuldstændig cyklus på 6 uger (doseringsskema 4/2).
Sixty-three patients received a starting dose of 50 mg sunitinib orally, once daily for 4 consecutive weeks followed by a 2-week rest period, to comprise a complete cycle of 6 weeks (Schedule 4/2).
Svampeinfektioner Urinvejsinfektioner Hudinfektioner Sepsis f ,*
Urinary tract infection Skin infectionse Sepsisf,*
Øsofagitis Abdominal distension Abdominalt ubehag Rektal blødning Gingival blødning Sår i munden Proktalgi
Abdominal distension Abdominal discomfort Rectal haemorrhage Gingival bleeding Mouth ulceration Proctalgia
Der blev udført et multinationalt, multicenter, enkeltarmet åbent fase 4-studie, som evaluerede virkningen og sikkerheden af sunitinib hos patienter med progressiv, fremskreden/metastatisk, veldifferentieret, inoperabel pNET.
A Phase 4 multinational, multi-centre, single-arm, open-label study evaluating the efficacy and safety of sunitinib was conducted in patients with progressive, advanced/metastatic, well-differentiated, unresectable pNET.
I et 1-måneds oralt gavagestudie (tvangsfodring) til fastlæggelse af dosisinterval (0, 10, 25, 75 og 200 mg/kg/dag), med CDD hos rasH2 transgene mus, blev der set karcinom og Brunnerkirtel hyperplasi i duodenum ved den højeste testdosis (200 mg/kg/dag).
In a 1-month, oral gavage dose-range finding study (0, 10, 25, 75, or 200 mg/kg/day) with continuous daily dosing in rasH2 transgenic mice, carcinoma and hyperplasia of Brunner's glands of the duodenum were observed at the highest dose (200 mg/kg/day) tested.
De hyppigste bivirkninger (≥ 10 %) var nedsat neutrofiltal (6 (20,7 %) patienter) og intrakraniel blødning (3 (10,3 %) patienter).
The most common (≥10%) treatment-related adverse events were neutrophil count decreased (6 [20.7%] patients) and haemorrhage intracranial (3[10.3%] patients).
Progressionsfri overlevelse [median, måneder (95% CI)] ved blindet, uafhængig, central gennemgang af tumor-vurdering
Progression-free survival [median, months (95% CI)] by blinded independent central review of tumour assessments a
Sunitinib skal bruges med forsigtighed hos patienter med risiko for disse hændelser, eller med disse hændelser i anamnesen (se pkt.
Use sunitinib with caution in patients who are at risk for, or who have a history of, these events (see section 4.8).
Et bekræftende åben, enkelt-arm, mulitcenterunderstudie, der evaluerede effekt og sikkerhed af sunitinib, blev udført hos patienter med mRCC, som var rekfraktære til tidligere cytokinbehandling.
A confirmatory, open-label, single-arm, multi-centre study evaluating the efficacy and safety of sunitinib was conducted in patients with MRCC who were refractory to prior cytokine therapy.
Perifer neuropati Paræstesi Hypæstesi Hyperæstesi
Neuropathy peripheral Paraesthesia Hypoaesthesia Hyperaesthesia
I det ene studie sås hypotyreose hos 15 (13,6%) af patienterne i behandling med sunitinib og hos 3 (2,9%) af patienterne i standardbehandling.
In 1 study, hypothyroidism was reported in 15 (13.6%) patients on sunitinib and 3 (2.9%) patients on standard of care.
Sjældne letale tilfælde er rapporteret i overvågning efter markedsføring.
Rare cases with fatal outcome have been observed in the postmarketing surveillance.
Skema 1 - Bivirkninger rapporteret i kliniske studier
Adverse reactions reported in clinical trials
Alvorlig hypertension blev rapporteret hos 10% af de pNETpatienter, der fik sunitinib, og hos 3% af de patienter, der fik placebo.
Severe hypertension was reported in 10% of pNET patients on sunitinib and 3% of patients on placebo.
Et fase 1/2-enkeltarmsstudie blev udført hos 6 pædiatriske patienter (i alderen 13-16 år) med fremskreden inoperabel GIST.
A Phase 1/2 single-arm, study was conducted in 6 paediatric patients (aged 13 years to 16 years) with advanced unresectable GIST.
Sjældne bivirkninger: forekommer hos op til 1 ud af 1.000 personer
Rare: may affect up to 1 in 1,000 people
Sutent 12,5 mg hårde kapsler Sutent 25 mg hårde kapsler Sutent 37,5 mg hårde kapsler Sutent 50 mg hårde kapsler
Sutent 12.5 mg hard capsules Sutent 25 mg hard capsules Sutent 37.5 mg hard capsules Sutent 50 mg hard capsules
Gulfarvet hud, misfarvet hud og unormal pigmentering u
Yellow skin, skin discolouration, and pigmentation disorder.
Farmakokinetikken var ens hos alle undersøgte populationer med solide tumorer og hos raske forsøgspersoner.
The PK were similar in all solid tumours populations tested and in healthy volunteers.
Hypertension sås hos ca. 33,9% af de behandlingsnaive mRCCpatienter, der fik sunitinib sammenlignet med 3,6% af patienterne, der fik IFN-α.
Hypertension was reported in approximately 33.9% of patients receiving sunitinib for treatment-naïve MRCC compared to 3.6% of patients receiving IFN-.
Dyspnø Epistaxis Hoste
Dyspnoea Epistaxis Cough
Gastrointestinale stromale tumorer
Gastrointestinal stromal tumours
Progressionsfri overlevelse [median, måneder (95% CI)] ved responsvurdering baseret på RECIST sammenholdt med investigatortumor-måling
Progression-free survival [median, months (95% CI)] by derived tumour response assessment based upon application of RECIST to investigator tumour assessments
Behandlingsrelaterede alvorlige bivirkninger blev set hos 23,7% af de patienter, som fik sunitinib, og hos 6,9% af de patienter, som fik IFN-αbehandling.
Treatment-related serious adverse events (TRSAEs) were reported in 23.7% of patients receiving sunitinib and in 6.9% of patients receiving IFN-α.
Forhøjet blodkreatinkinase Forhøjet thyroideastimulerend e hormon (TSH)
Blood creatine phosphokinase increased Blood thyroid stimulating hormone increased
Svær hypertension forekom hos 12% af de behandlingsnaive patienter på sunitinib og ≤1% af patienterne på IFN-α.
Severe hypertension was reported in 12% of treatment-naïve patients on sunitinib and < 1% of patients on IFN-.
Der er set levertoksicitet hos patienter behandlet med sunitinib.
Hepatotoxicity has been observed in patients treated with sunitinib.
30 mg/m2 dagligt og publicerede, tilgængelige data (20 pædiatriske eller unge voksne patienter med GIST) indikerede, at sunitinib medførte stabilisering af sygdommen hos 18 ud af 26 (69,2 %) af patienterne, enten efter behandlingssvigt med eller intolerance over for imatinib (16 ud af 21 patienter med stabil sygdom) eller de novo/efter operation (2 ud af 5 patienter med stabil sygdom).
Evidence from a Phase 1/2 study of oral sunitinib conducted in 6 paediatric patients with GIST aged 13 years to 16 years who received sunitinib on Schedule 4/2, at doses ranging between 15 mg/m daily and 30 mg/m daily, and available published data (20 paediatric or young adult patients with GIST) indicated that sunitinib treatment resulted in disease stabilization in 18 of 26 (69.2%) patients, either after imatinib failure or intolerance (16 patients with stable disease out of 21), or de novo/after surgery (2 patients with stable disease out of 5).
Progressionsfri overlevelse [median, måneder (95% CI)] ved investigatorvurdering
Progression-free survival [median, months (95% CI)] by Investigator Assessment a
Der forekom lungehændelser hos ca. 22,2% af patienterne med solide tumorer, herunder GIST og mRCC, som blev behandlet med sunitinib i kliniske studier.
Approximately 22.2% of patients with solid tumours, including GIST and MRCC, who received sunitinib in clinical trials experienced pulmonary events.
Sunitinib har vist forlængelse af QTcF-interval (Fridericias korrektion) ved ca. dobbelt terapeutisk koncentration.
At approximately twice therapeutic concentrations, sunitinib has been shown to prolong the QTcF interval (Fridericia corrected QT interval).
Neuroendokrine tumorer i pancreas
Pancreatic neuroendocrine tumours
Sunitinib er ikke klastogent i knoglemarv hos rotter in vivo.
Sunitinib was not clastogenic in rat bone marrow in vivo.
Til GIST og mRCC er den anbefalede dosis af Sutent 50 mg 1 gang dagligt indtaget oralt i 4 på hinanden følgende uger og derefter 2 ugers pause (doseringsskema 4/2).
For GIST and MRCC, the recommended dose of Sutent is 50 mg taken orally once daily, for 4 consecutive weeks, followed by a 2-week rest period (Schedule 4/2) to comprise a complete cycle of 6 weeks.
Fortæl det til lægen, hvis du får nogle af de følgende symptomer: smerter i den øverste del af maven, kvalme, opkastning og feber.
Tell your doctor if you develop any of the following signs and symptoms: pain in the area of the stomach (upper abdomen), nausea, vomiting, and fever.
Det vil sige, de patienter, som var resistente over for imatinib, (dvs. dem som udviklede sygdomsprogression under eller efter behandling med imatinib) eller som udviste intolerans over for imatinib (dvs. dem, som udviklede signifikant toksicitet under behandling med imatinib, og hvor yderligere behandling var udelukket).
The clinical safety and efficacy of sunitinib has been studied in the treatment of patients with GIST who were resistant to imatinib (i.e., those who experienced disease progression during or following treatment with imatinib) or intolerant to imatinib (i.e., those who experienced significant toxicity during treatment with imatinib that precluded further treatment), the treatment of patients with MRCC, and the treatment of patients with unresectable pNET.
Renal elimination af uomdannet aktivt stof og metabolitter sker med 16% af den indgivne dosis.
Excretion is primarily via faeces (61%), with renal elimination of unchanged active substance and metabolites accounting for 16% of the administered dose.
- Svulster i nyrecellerne, hvor kræften har spredt sig til andre dele af kroppen (mRCC).
- Metastatic renal cell carcinoma (MRCC), a type of kidney cancer that has spread to other parts of the body.
Hos kaninfostre ses udviklingsforstyrrelser i form af hareskår ved plasmakoncentrationer på omtrent samme niveau som i klinikken og i form af hareskår og ganespalte ved plasmakoncentrationer, der er 2,7 gange højere end human eksponering.
In rabbits, developmental effects consisted of increased incidence of cleft lip at plasma exposure levels approximately equal to that observed in clinic, and cleft lip and cleft palate at plasma exposure levels 2.7 times the systemic exposure in humans.
I det andet studie sås hypotyreose hos i alt 31 (13%) af patienterne på sunitinib og hos 2 (0,8%) af patienterne på capecitabin.
In the other study hypothyroidism was reported in a total of 31 (13%) patients on sunitinib and 2 (0.8%) patients on capecitabine.
Sunitinib bør seponeres hos patienter, der udvikler TMA, og øjeblikkelig behandling er påkrævet.
Sunitinib therapy should be discontinued in patients who develop TMA and prompt treatment is required.
Overproduktion af skjoldbruskkirtlens hormoner, hvilket medfører øget stofskifte i hvile.
• Overproduction of thyroid hormones which increases the amount of energy the body uses at rest.
Hovedparten af disse tilfælde blev set hos patienter, som havde fået behandling med bisfosfonater intravenøst før eller samtidig med Sutent-behandlingen.
The majority of cases were reported in patients who had received prior or concomitant treatment with intravenous bisphosphonates, for which ONJ is an identified risk.
Posteriort reversibelt encefalopatisyndrom
Posterior reversible encephalopathy syndrome*
Et underbyggende, åbent, fase 2, multicenterstudie undersøgte effekt og sikkerhed af monoterapi med sunitinib 50 mg dagligt i skema 4/2 hos patienter med inoperabel pNET.
A supportive Phase 2, open-label, multi-centre study evaluated the efficacy and safety of single-agent sunitinib 50 mg daily on Schedule 4/2 in patients with unresectable pNET.
Hos kaniner er der konstateret nedsat vægt af den drægtige livmoder, et nedsat antal levende fostre som følge af forøget antal resorptioner, forøget postimplantationstab og tab af hele kuldet hos 4/6 drægtige hunner ved plasmakoncentrationer, der er 3 gange højere end human eksponering.
reductions in gravid uterine weights and number of live foetuses were due to increases in the number of resorptions, increases in postimplantation loss and complete litter loss in 4 of 6 pregnant females at plasma exposure levels 3 times the systemic exposure in humans.
Kombinationen med CYP3A4-induktorer bør derfor undgås, eller det bør overvejes at vælge et andet lægemiddel til samtidig til samtidig behandling med ingen eller minimalt potentiale til at inducere CYP3A4.
Combination with CYP3A4 inducers should therefore be avoided, or selection of an alternate concomitant medicinal product, with no or minimal potential to induce CYP3A4 should be considered.
Der blev ikke rapporteret om alvorlige eller grad 5 bivirkninger i studiet.
There were no serious adverse events (SAEs) or Grade 5 adverse drug reactions reported in this study.
Der er rapporteret om tilfælde af osteonekrose af kæben hos patienter, der er blevet behandlet med Sutent.
Cases of ONJ have been reported in patients treated with Sutent.
Kontakt din læge omgående, hvis du oplever symptomer på lavt blodsukker (træthed, hjertebanken, øget svedafsondring, øget appetit og tab af bevidsthed).
Notify your doctor as soon as possible if you experience any signs and symptoms of low blood sugar (fatigue, palpitations, sweating, hunger and loss of consciousness).
Fortæl det altid til lægen eller sundhedspersonalet, hvis du bruger anden medicin, har brugt det for nylig eller skal til at bruge det.
Tell your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines, including medicines obtained without a prescription and even those not prescribed.
I kliniske studier er der set sjældne tilfælde af TLS, nogle var letale, og hos patienter efter markedsføring, der er blevet behandlet med sunitinib.
Cases of TLS, some fatal, have been rarely observed in clinical trials and have been reported in postmarketing surveillance in patients treated with sunitinib.
Hos 17 patienter (4,5%), der fik sunitinib, forekom blødning i grad 3 eller højere sammenlignet med 5 (1,7%) patienter, der fik IFN-α.
Seventeen (4.5%) patients on sunitinib versus 5 (1.7%) patients on IFN-α experienced Grade 3 or greater bleeding events.
De hyppigste bivirkninger (≥ 10 %) hos patienterne i begge grupper tilsammen var nedsat neutrofiltal (6 patienter (20,7 %); og intrakranial blødning (3 patienter (10,3 %)) (se pkt.
The most common (≥10%) reported treatment-related adverse events in patients in both groups combined were neutrophil count decreased (6 patients [20.7%]) and haemorrhage intracranial (3 patients [10.3%]) (see section 4.8).
- Hvis du har eller har haft trombotisk mikroangiopati (TMA), en sygdom hvor der er beskadigelse på de mindste blodkar.
- If you have or have had damage to the smallest blood vessels known as thrombotic microangiopathy (TMA).
Der sås forhøjet T4 hos 2 (0,8%) patienter på sunitinib og hos 1 (0,4%) patient på i behandling med capecitabin.
T4 increase was reported in 2 (0.8%) patients on sunitinib and 1 (0.4%) patient on capecitabine.
I kliniske studier og efter markedsføring er der set tilfælde af pulmonalblødninger, som i nogle tilfælde var letale, hos patienter, der er blevet behandlet med sunitinib mod mRCC, GIST og lungecancer.
Cases of pulmonary haemorrhage, some with a fatal outcome, have been observed in clinical trials and have been reported in postmarketing experience in patients treated with sunitinib for MRCC, GIST, and lung cancer.
Kombinationen med CYP3A4-hæmmerne bør derfor undgås, eller det bør overvejes at vælge et andet lægemiddel til samtidig behandling med ingen eller minimal potentiale til at hæmme CYP3A4.
Combination with CYP3A4 inhibitors should therefore be avoided, or the selection of an alternate concomitant medicinal product with no or minimal potential to inhibit CYP3A4 should be considered.
- Lægen har ordineret Sutent til dig personligt.
- This medicine has been prescribed for you only.
- Hvis du har eller har haft problemer med leveren.
- If you have or have had liver problems.
Nekrotiserende fasciitis
Necrotising fasciitis*
Ingen af disse patienter fik seponeret behandlingen med sunitinib permanent.
Sunitinib was not permanently discontinued in any of these patients.
Et ublindet fase 2-studie blev udført hos 29 patienter, herunder 27 pædiatriske patienter (i alderen 316 år) og 2 unge voksne patienter (i alderen 18-19 år) med recidiverende/progressiv/refraktær højgrads gliom eller ependymom.
A phase 2 open-label study was conducted in 29 patients comprised of 27 paediatric patients (aged 3 years to 16 years) and 2 young adult patients (aged 18 years to 19 years) with recurrent/progressive/refractory high grade glioma (HGG) or ependymoma.
Et fase 1-dosiseskaleringsstudie med oral sunitinib blev udført hos 35 patienter, herunder 30 pædiatriske patienter (i alderen 3-17 år) og 5 unge voksne patienter (i alderen 18-21 år) med refraktære, solide tumorer, hvoraf de fleste havde en hjernetumor som primær diagnose.
A Phase 1 dose-escalation study of oral sunitinib was conducted in 35 patients comprised of 30 paediatric patients (aged 3 years to 17 years) and 5 young adult patients (aged 18 to 21 years), with refractory solid tumours, the majority of whom had a primary diagnosis of brain tumour.
Blødning (eksklusive epistaxis) sås hos 21,7% af de patienter, som fik sunitinib i fase 3 pNET-studiet, sammenlignet med 9,85% af de patienter, som fik placebo.
Bleeding events, excluding epistaxis, were reported in 21.7% of patients receiving sunitinib in the Phase 3 pNET study compared to 9.85% of patients receiving placebo (see section 4.4)
Desuden var det beregnede startdosisinterval ifølge publicerede data 16,6 mg/m 2 til 36 mg/m 2 og steg til doser helt op til 40,4 mg/m 2 (måtte ikke overstige en totaldosis på 50
Furthermore, according to the published literatures in paediatric patients with GIST, the calculated starting dose ranged from 16.6 mg/m to 36 mg/m increased to doses as high as 40.4 mg/m