natgillin/translations-raw huggingface dataset:
Udslæt (75%) og diarré (54%) var de mest almindelige rapporterede bivirkninger.
Rash (75%) and diarrhoea (54%) were the most commonly reported adverse drug reactions (ADRs).
De fleste var af grad 1/ 2, og intervention var ikke nødvendig.
Most were Grade 1/ 2 in severity and manageable without intervention.
Udslæt og diarré af grad 3/ 4 forekom hos hhv.
Grade 3/ 4 rash and diarrhoea occurred in 9% and 6%, respectively in Tarceva-treated patients and each resulted in study discontinuation in 1% of patients.
9% og 6% af de Tarceva- behandlede patienter, og hver af dem medførte afbrydelse af behandlingen hos 1%
Dose reduction for rash and diarrhoea was needed in 6% and 1% of patients, respectively.
I studie BR. 21 var den mediane tid indtil starten af udslæt 8 dage og den mediane tid indtil starten af diarré 12 dage.
In study BR.21, the median time to onset of rash was 8 days, and the median time to onset of diarrhoea was 12 days.
De bivirkninger, som i det pivotale studie BR. 21 optrådte hyppigere (≥3%) hos Tarceva- behandlede patienter end hos patienter, som fik placebo, og som optrådte hos mindst 10% af patienterne i Tarceva- gruppen, er sammenfattet i henhold til National Cancer Institute- Common Toxicity Criteria (NCI- CTC) Grade i tabel 1.
6 Adverse events occurring more frequently (≥ 3%) in Tarceva-treated patients than in the placebo group in the pivotal study BR.21, and in at least 10% of patients in the Tarceva group, are summarised by National Cancer Institute-Common Toxicity Criteria (NCI-CTC) Grade in Table 1.
Meget almindelige bivirkninger i studie BR. 21
Very common ADRs in study BR.21
Erlotinib N = 485 Alle
Erlotinib N = 485
NCI- CTC grad
NCI-CTC
grader
Grade Grade
3 4 grader 3
3 4 Grade 3
MedDRA termer Totalt antal patienter med uønsket
MedDRA Preferred Term Total patients with any AE Infections and infestations
Infektion * Metabolisme og ernæring
Infection* Metabolism and nutrition disorders
Anoreksi Øjne
Anorexia Eye disorders
Konjunctivitis Keratoconjunctivitis sicca Luftveje, thorax og mediastinum
Conjunctivitis Keratoconjunctivitis sicca Respiratory, thoracic and mediastinal disorders
Dyspnø Hoste Mave- tarmkanalen
Dyspnoea Cough Gastrointestinal disorders
Diarré ** Kvalme Opkastning Stomatitis Mavesmerter Hud og subkutane væv
Diarrhoea** Nausea Vomiting Stomatitis Abdominal pain Skin and subcutaneous tissue disorders
Udslæt *** Kløe Tør hud Almene symptomer og reaktioner på administrationsstedet
Rash*** Pruritus Dry skin General disorders and administration site conditions
Svære infektioner, med eller uden neutropeni, har omfattet pneumoni, sepsis og cellulitis. ** Kan føre til dehydrering, hypokaliæmi og nyreinsufficiens. *** Udslæt herunder dermatitis acneiform.
* Severe infections, with or without neutropenia, have included pneumonia, sepsis, and cellulitis. ** Can lead to dehydration, hypokalemia and renal failure. *** Rash included dermatitis acneiform.
Pancreas- cancer (samtidig administration af Tarceva og gemcitabin i studiet PA. 3):
Pancreatic cancer (Tarceva administered concurrently with gemcitabine in study PA.3):
De mest almindelige bivirkninger hos patienter med pancreas- cancer, som fik Tarceva 100 mg plus gemcitabin i det pivotale studie PA. 3, var træthed, udslæt og diarré.
The most common adverse reactions in pivotal study PA.3 in pancreatic cancer patients receiving Tarceva 100 mg plus gemcitabine were fatigue, rash and diarrhoea.
I gruppen, som fik Tarceva plus gemcitabin, blev der rapporteret om udslæt og diarré af grad 3/ 4 hos 5% af patienterne.
In the Tarceva plus gemcitabine arm, Grade 3/ 4 rash and diarrhoea were each reported in 5% of patients.
Både udslæt og diarré medførte
The median time to onset of rash and diarrhoea was 10 days and 15 days, respectively.
7 dosisreduktion hos 2% af patienterne og afbrydelse af studiet hos op til 1% af patienterne, som fik Tarceva plus gemcitabin.
Rash and diarrhoea each resulted in dose reductions in 2% of patients, and resulted in study discontinuation in up to 1% of patients receiving Tarceva plus gemcitabine.
Bivirkninger, som i det pivotale studie PA. 3 optrådte hyppigere (≥ 3%) hos patienter behandlet med Tarceva 100 mg plus gemcitabin end hos patienter behandlet med placebo plus gemcitabin, og som optrådte hos mindst 10% af patienterne i gruppen, som fik Tarceva 100 mg plus gemcitabin, er sammenfattet i tabel 2 i henhold til National Cancer Institute Common Toxicity Criteria (NCI- CTC).
7 Adverse events occurring more frequently (≥ 3%) in Tarceva 100 mg plus gemcitabine-treated patients than in the placebo plus gemcitabine group in the pivotal study PA.3, and in at least 10% of patients in the Tarceva 100 mg plus gemcitabine group, are summarised by National Cancer Institute-Common Toxicity Criteria (NCI-CTC) Grade in Table 2.
studie PA. 3 (100 mg gruppen)
Very common ADRs in study PA.3 (100 mg cohort)
Erlotinib N=259 Alle
Erlotinib N = 259 Any
NCI- CTC Grad MedDRA termer Totalt antal patienter med bivirkninger Infektioner og parasitære sygdomme
3
grader% 99
Grade Grade
4 grader%% 22 97
% 22
< 1 24
< 1
Vægttab Psykiske forstyrrelser
Weight decreased Psychiatric disorders
0 29
29
Depression Nervesystemet
Depression Nervous system disorders
0 14
14
Hovedpine Neuropati Luftveje, thorax og mediastinum Hoste
Headache Neuropathy Respiratory, thoracic and mediastinal disorders
0 10 < 1 10
< 1 1
Mave- tarmkanalen
Cough Gastrointestinal disorders
0 11
11
Diarré ** Stomatitis Dyspepsi Flatulens Hud og subkutane væv
Diarrhoea** Stomatitis Dyspepsia Flatulence Skin and subcutaneous tissue disorders
< 1 36 0 12 0 13 0 9
36 12 13 9
Udslæt *** Alopeci Almene symptomer og reaktioner på administrationsstedet
Rash*** Alopecia General disorders and administration site conditions
5 0
0 0
0 30 0 11
30 11
Pyreksi Træthed Rigor
Pyrexia Fatigue Rigors
0 30 2 70 0 9
30 70 9
* Svære infektioner, med eller uden neutropeni, har omfattet pneumoni, sepsis og cellulitis. ** Kan føre til dehydrering, hypokaliæmi og nyreinsufficiens. *** Udslæt herunder dermatitis acneiform.
* Severe infections, with or without neutropenia, have included pneumonia, sepsis, and cellulitis. ** Can lead to dehydration, hypokalemia and renal failure. *** Rash included dermatitis acneiform.
248- 101 (ovariecancer),
Safety evaluation of Tarceva is based on the data from 759 patients treated with at least one 150 mg dose of Tarceva monotherapy during Phase III NSCLC study BR.21, Phase II NSCLC study A248-1007, and three Phase II studies in populations other than NSCLC:
8 A248- 1003 (hoved- halskræft) og OSI2288g (metastatisk brystkræft) og fra 285 patienter, som fik Tarceva 100 eller 150 mg plus gemcitabin i fase III pancreas- cancer- studiet PA. 3.
248-101 (ovarian cancer), A248-1003 (head and neck cancer), and OSI2288g (metastatic breast cancer) and the 285 patients who received Tarceva 100 or 150 mg plus gemcitabine in the phase III pancreatic cancer study PA.3.
Følgende betegnelser anvendes for at graduere bivirkningerne efter hyppighed: 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), herunder enkeltstående indberetninger.
8 The following terms are used to rank the undesirable effects by frequency: very common (> 1/ 10); common (> 1/ 100 ,< 1/10); uncommon (> 1/1 ,000, < 1/100); rare (> 1/10,000, < 1/1000); very rare (< 1/10,000) including isolated reports.
Meget almindeligt forekommende bivirkninger fremgår af tabel 1 og 2, mens bivirkninger med anden hyppighed er sammenfattet herunder:
Very common ADR’ s are presented in Tables 1 and 2, ADR ’ s in other frequency categories are summarized below.
4. 5) og nogle gange med samtidig administration af NSAIDs.
In clinical studies, some cases have been associated with concomitant warfarin administration (see section 4.5) and some with concomitant NSAID administration.
Almindelig (i PA. 3):
Common (in PA.3):
Alopeci.
Alopecia.
Tør hud.
Dry skin.
Panaritium.
Paronychia.
Hirsutisme, øjenvippe - / øjenbrynforandringer og skrøbelige og løse negle.
Hirsutism, eyelash/ eyebrow changes and brittle and loose nails.
Meget almindelig (i PA. 3) Almindelig (i BR. 21):
Very common (in PA.3) Common (in BR.21):
Abnorme leverfunktionstests (inklusive øget alaninaminotransferase [ALAT], aspartataminotransferase [ASAT] og bilirubin).
Liver function test abnormalities (including increased alanine aminotransferase [ALT], aspartate aminotransferase [AST], bilirubin).
Stigningerne var normalt af let eller moderat sværhedsgrad, forbigående eller forbundet med levermetastaser.
These were mainly mild or moderate in severity, transient in nature or associated with liver metastases.
Der er rapporteret om sjældne tilfælde af leverinsifficiens (herunder fatale) under anvendelsen af Tarceva.
Rare cases of hepatic failure (including fatalities) have been reported during use of Tarceva.
4. 4).
Confounding factors have included pre-existing liver disease or concomitant hepatotoxic medications (see section 4.4).
Keratitis.
Keratitis.
Conjunctivitis i studie PA. 3.
Conjunctivitis in study PA.3.
Ulceration af cornea, som en komplikation til mucokutan inflammation, er rapporteret meget sjældent hos patienter, der får Tarceva.
Corneal ulcerations have been reported very rarely in patients receiving Tarceva as a complication of mucocutaneous inflammation.
Epistaxis.
Epistaxis.
4. 4).
Serious interstitial lung disease (ILD), including fatalities, in patients receiving Tarceva for treatment of NSCLC or other advanced solid tumours (see section 4.4).
På basis af data fra disse studier kan der forekomme svære, uønskede hændelser som f. eks. diarré, udslæt og muligvis øget aktivitet af leveraminotransferaser i doser over den anbefalede dosis.
Based on the data from these studies, severe adverse events such as diarrhoea, rash and possibly increased activity of liver aminotransferases may occur above the recommended dose.
Farmakoterapeutisk klassifikation: antineoplastisk stof, ATC- kode:
Pharmacotherapeutic group: antineoplastic agent, ATC code:
Erlotinib er en epidermal vækstfaktorreceptor/ human epidermal vækstfaktorreceptor type 1 (EGFR også kendt som HER1) tyrosinkinase- hæmmer.
9 Erlotinib is an epidermal growth factor receptor/ human epidermal growth factor receptor type 1 (EGFR also known as HER1) tyrosine kinase inhibitor.
I ikke- kliniske modeller medfører hæmning af EGFR phosphortyrosin cellestase og/ eller celledød.
In non-clinical models, inhibition of EGFR phosphotyrosine results in cell stasis and/ or death.
Effekt og sikkerhed af Tarceva blev dokumenteret i et randomiseret, dobbeltblindet, placebokontrolleret studie (BR. 21) hos 731 patienter med lokalt fremskreden eller metastatisk NSCLC efter behandlingssvigt af mindst et kemoterapiregime.
The efficacy and safety of Tarceva was demonstrated in a randomised, double-blind, placebo-controlled trial (BR.21), in 731 patients with locally advanced or metastatic NSCLC after failure of at least one chemotherapy regimen.
Patienterne blev randomiserede i forholdet 2: 1 til behandling med Tarceva 150 mg eller placebo oralt én gang daglig.
Patients were randomised 2:1 to receive Tarceva 150 mg or placebo orally once daily.
Ca. to tredjedele af patienterne var mænd og ca. en tredjedel havde en baseline ECOG performance status (PS) på 2 og 9% havde en baseline ECOG PS på 3.
About two-thirds of the patients were male and approximately one-third had a baseline ECOG performance status (PS) of 2, and 9% had a baseline ECOG PS of 3.
36% og 37% af alle patienter havde tidligere fået taxan- terapi.
Ninety-three percent and 92% of all patients in the Tarceva and placebo groups, respectively, had received a prior platinum-containing regimen and 36% and 37% of all patients, respectively, had received a prior taxane therapy.
Den justerede hazard ratio (HR) for død i Tarceva- gruppen i forhold til placebogruppen var 0, 73 (95% konfidensinterval; 0, 60 til 0, 87) (p = 0, 001).
The adjusted hazard ratio (HR) for death in the Tarceva group relative to the placebo group was 0.73 (95% CI, 0.60 to 0.87) (p = 0.001).
31, 2% og 21, 5% i live i Tarceva - og placebogruppen.
The percent of patients alive at 12 months was 31.2% and 21.5%, for the Tarceva and placebo groups, respectively.
4, 1 til 6, 3 måneder).
The median overall survival was 6.7 months in the Tarceva group (95% CI, 5.5 to 7.8 months) compared with 4.7 months in the placebo group (95% CI, 4.1 to 6.3 months).
Virkningen af Tarceva på samlet overlevelse var sammenlignelig hos patienter med baseline performance status (ECOG) på 2- 3 (HR = 0, 77; konfidensinterval 0, 6- 1, 0) eller 0- 1 (HR = 0, 73; konfidensinterval 0, 6 - 0, 9), mandlige patienter (HR = 0, 76; konfidensinterval 0, 6- 0, 9) eller kvindelige patienter (HR = 0, 80, konfidensinterval 0, 6- 1, 1), patienter < 65 år (HR = 0, 75; konfidensinterval 0, 6- 0, 9) eller ældre patienter (HR = 0, 79; konfidensinterval 0, 6- 1, 0), patienter med ét tidligere regime (HR = 0, 76; konfidensinterval 0, 6- 1, 0) eller mere end ét tidligere regime (HR = 0, 75; konfidensinterval 0, 6- 1, 0), kaukasiere (HR = 0, 79; konfidensinterval 0, 6- 1, 0) eller asiatiske patienter (HR = 0, 61; konfidensinterval 0, 4- 1, 0), patienter med adenokarcinom (HR = 0, 71; konfidensinterval 0, 6- 0, 9) eller planocellulært karcinom (HR = 0, 67; konfidensinterval 0, 5- 0, 9), men ikke hos patienter med anden histologi (HR 1, 04; konfidensinterval 0, 7- 1, 5), patienter med stadie IV sygdom ved diagnosetidspunktet (HR = 0, 92; konfidensinterval 0, 7- 1, 2) eller < stadie IV sygdom ved diagnosetidspunktet (HR = 0, 65; konfidensinterval 0, 5- 0, 8).
The effect of Tarceva on overall survival was similar in patients with a baseline performance status (ECOG) of 2-3 (HR = 0.77, CI 0.6-1.0) or 0-1 (HR = 0.73, 0.6-0.9), male (HR = 0.76, CI 0.6-0.9) or female patients (HR = 0.80, CI 0.6-1.1), patients < 65 years of age (HR = 0.75, CI 0.6-0.9) or older patients (HR = 0.79, CI 0.6-1.0), patients with one prior regimen (HR = 0.76, CI 0.6-1.0) or more than one prior regimen (HR = 0.75, CI 0.6-1.0), Caucasian (HR = 0.79, CI 0.6-1.0) or Asian patients (HR = 0.61, 0.4-1.0), patients with adenocarcinoma (HR = 0.71, CI 0.6-0.9) or squamous cell carcinoma (HR = 0.67, CI 0.5-0.9), but not in patients with other histologies (HR 1.04, CI 0.7-1.5), patients with stage IV disease at diagnosis (HR = 0.92, CI 0.7-1.2) or < stage IV disease at diagnosis (HR = 0.65, 0.5-0.8).
Patienter, der aldrig har røget havde en større effekt af erlotinib (overlevelse HR = 0, 42; konfidensinterval 0, 28- 0, 64) sammenlignet med rygere eller ex- rygere (HR = 0, 87; konfidensinterval 0, 71- 1, 05).
Patients who never smoked had a much greater benefit from erlotinib (survival HR = 0.42, CI 0.28-0.64) compared with current or ex-smokers (HR = 0.87, CI 0.71-1.05).
Hazard ratio for patienter med EGFR- positive tumorer var 0, 68 (konfidensinterval 0, 49- 0, 94) og 0, 93 (konfidensinterval (0, 63- 1, 36) for patienter med EGFR- negative tumorer (defineret ved IHC under anvendelse af EGFR pharmDx kit og definerende EGFR- negativ som farvning af mindre end 10% af tumorcellerne).
In the 45% of patients with known EGFR-expression status, the hazard ratio was 0.68 (CI 0.49-0.94) for patients with EGFR-positive tumours and 0.93 (CI 0.63-1.36) for patients with EGFR-negative tumours (defined by IHC using EGFR pharmDx kit and defining EGFR-negative as less than 10% tumour cells staining).
Hos de resterende 55% af patienterne med ukendt EGFR- ekspressionsstatus var hazard ratio 0, 77 (konfidensinterval 0, 61- 0, 98).
In the remaining 55% of patients with unknown EGFR-expression status, the hazard ratio was 0.77 (CI 0.61-0.98).
10 Den mediane PFS var 9, 7 uger i Tarceva- gruppen (95% konfidensinterval; 8, 4 til 12, 4 uger) sammenlignet med 8, 0 uger i placebo- gruppen (95% konfidensinterval; 7, 9 til 8, 1 uger).
The median PFS was 9.7 weeks in the Tarceva group (95% CI, 8.4 to 12.4 weeks) compared with 8.0 weeks in the placebo group (95% CI, 7.9 to 8.1 weeks).
RECIST var 8, 9% i Tarceva- gruppen (95% konfidensinterval; 6, 4 til 12, 0%).
The objective response rate by RECIST in the Tarceva group was 8.9% (95% CI, 6.4 to 12.0).
De første 330 patienter blev vurderet centralt (responsrate 6, 2%); 401 patienter blev vurderet af investigator (responsrate 11, 2%).
The first 330 patients were centrally assessed (response rate 6.2%); 401 patients were investigator- assessed (response rate 11.2%).
9, 7 til 57, 6+ uger.
The median duration of response was 34.3 weeks, ranging from 9.7 to 57.6+ weeks.
44, 0% og 27, 5% i Tarceva - og placebo- gruppen (p = 0, 004).
The proportion of patients who experienced complete response, partial response or stable disease was 44.0% and 27.5%, respectively, for the Tarceva and placebo groups (p = 0.004).
RECIST).
10 A survival benefit of Tarceva was also observed in patients who did not achieve an objective tumour response (by RECIST).
Evidensen herfor var en hazard ratio for død på 0, 82 (95% konfidensinterval; 0, 68 til 0, 99) hos patienter, hvis bedste respons var stabil eller progredierende sygdom.
This was evidenced by a hazard ratio for death of 0.82 (95% CI, 0.68 to 0.99) among patients whose best response was stable disease or progressive disease.
Pancreas- cancer (samtidig administration af Tarceva og gemcitabin i studie PA. 3):
Pancreatic cancer (Tarceva administered concurrently with gemcitabine in study PA.3):
Effekt og sikkerhed af Tarceva i kombination med gemcitabin som 1. linie behandling blev vurderet i et randomiseret, dobbeltblindt, placebokontrolleret studie hos patienter med lokalt fremskreden inoperabel eller metastaserende pancreas- cancer.
The efficacy and safety of Tarceva in combination with gemcitabine as a first-line treatment was assessed in a randomised, double-blind, placebo-controlled trial in patients with locally advanced, unresectable or metastatic pancreatic cancer.
(1000 mg/ m2, serie 1 på dag 1, 8, 15, 22, 29, 36 og 43 i en 8 ugers serie; serie 2 og efterfølgende serier på dag 1, 8 og 15 i en 4 ugers serie [vedr. godkendt dosis og doseringsskema for pancreas cancer se produktresuméet for gemcitabin]).
Patients were randomised to receive Tarceva or placebo once daily on a continuous schedule plus gemcitabine IV (1000 mg/ m2, Cycle 1 - Days 1, 8, 15, 22, 29, 36 and 43 of an 8 week cycle; Cycle 2 and subsequent cycles - Days 1, 8 and 15 of a 4 week cycle [approved dose and schedule for pancreatic cancer, see the gemcitabine SPC]).
Bortset fra at der var lidt flere kvinder i erlotinib/ gemcitabin- armen end i placebo/ gemcitabin- armen var demografi og sygdomskarakteristika ved baseline ens for de to behandlingsgrupper, 100 mg Tarceva plus gemcitabin og placebo plus gemcitabin:
Baseline demographic and disease characteristics of the patients were similar between the 2 treatment groups, 100 mg Tarceva plus gemcitabine or placebo plus gemcitabine, except for a slightly larger proportion of females in the erlotinib/ gemcitabine arm compared with the placebo/ gemcitabine arm:
Baseline Kvinder ECOG performance status (PS) = 0 ved baseline ECOG performance status (PS) = 1 ved baseline ECOG performance status (PS) = 2 ved baseline Metastserende sygdom ved baseline
Baseline Females Baseline ECOG performance status (PS) = 0 Baseline ECOG performance status (PS) = 1 Baseline ECOG performance status (PS) = 2 Metastatic disease at baseline
Overlevelsen blev evalueret hos intent- to- treat- populationen på grundlag af follow- up - overlevelsesdata.
Survival was evaluated in the intent-to-treat population based on follow-up survival data.
Konfidens -
CI of
interval of
P-
P -
Outcome
Resultat
(months)
(måneder) (måneder)
(months) (months) Overall Population
(måneder) interval af Δ
CI of Δ
HR HR
HR HR
Samlet population Median samlet overlevelse
Median overall survival
- 0, 54- 1, 64
-0.54-1.64
overlevelse
Mean overall survival
Metastatisk population Median samlet overlevelse
Metastatic Population Median overall survival
Lokalt fremskreden population Median samlet overlevelse
Locally Advanced Population Median overall survival
Samlet overlevelse – alle patienter 1, 0
11 Overall Survival – All Patients 1.0
0, 9 Sandsynlighed for overlevelse
0.9
HR = 0, 82 (95% konfidensinterval:
HR = 0.82 (95% CI:
0, 69; 0, 98), p = 0, 028
0.6 9, 0.98), p = 0.028
Tarceva + gemcitabine (n = 261)
Tarceva + gemcitabine (n = 261)
0, 3 0, 2
0.3 0.2 0.1 0.0
Placebo +
Placebo + gemcitabine (n = 260) Median OS = 6.0 months
0, 1 gemcitabine (n = 260) Median samlet overlevelse = 6, 0 0, 0
Median OS = 6.4 months
12 Samlet overlevelse – patienter med fjernmetastaser 1, 0
Overall Survival – Patients with Distant Metastases 1.0
HR = 0, 80 (95% konfidensinterval:
HR = 0.80 (95% CI:
0, 66; 0, 98), p = 0, 029
0.6 6, 0.98), p = 0.029
Tarceva + gemcitabine (n = 200)
Tarceva + gemcitabine (n = 200)
Placebo +
Placebo +
Median samlet overlevelse = 5, 93 måneder
Median OS = 5.93 months
0, 1 gemcitabine (n = 197) Median samlet overlevelse = 5, 06 måneder 0, 0
0.1 gemcitabine (n = 197) Median OS = 5.0 6 months 0.0
En post- hoc analyse viste, at patienter med god klinisk status ved baseline (lav smerte intensitet, god QoL og god PS) kunne opnå mest gavn af behandling med Tarceva.
In a post-hoc analysis, patients with favourable clinical status at baseline (low pain intensity, good QoL and good PS) may derive more benefit from Tarceva.
Den gavnlige effekt ses ved tilstedeværelsen af en lav smerte- intensitetsscore.
The benefit is mostly driven by the presence of a low pain intensity score.
En post- hoc analyse viste, at patienter, der blev behandlet med Tarceva og fik udslæt, havde en længere samlet overlevelse sammenlignet med patienter, som ikke fik udslæt (median samlet overlevelse 7, 2 måneder versus 5 måneder, HR: 0, 61).
In a post-hoc analysis, patients on Tarceva who developed a rash had a longer overall survival compared to patients who did not develop rash (median OS 7.2 months vs 5 months, HR:0.61).
90% af patienterne, der blev behandlet med Tarceva, fik udslæt inden for de første 44 dage.
90% of patients on Tarceva developed rash within the first 44 days.
4 timer.
A fter oral administration, erlotinib peak plasma levels are obtained in approximately 4 hours after oral dosing.
Et studie hos raske frivillige estimerede den absolutte biotilgængelighed til 59%.
A study in normal healthy volunteers provided an estimate of the absolute bioavailability of 59%.
I et studie hos 4 patienter (3 med ikke- småcellet lungecancer [NSCLC] og 1 med larynxcancer), som fik 150 mg Tarceva dagligt oralt, viste tumorprøver fra kirurgiske ekscisioner på behandlingsdag 9 en samlet gennemsnitlig koncentration af erlotinib i tumorvæv på 1, 185 ng/ g væv.
In a study of 4 patients (3 with non-small cell lung cancer [NSCLC], and 1 with laryngeal cancer) receiving 150 mg daily oral doses of Tarceva, tumour samples from surgical excisions on Day 9 of treatment revealed tumour concentrations of erlotinib that averaged 1,185 ng/g of tissue.
5- 161%) af peak- plasmakoncentrationerne i steady- state.
This corresponded to an overall average of 63% (range 5-161%) of the steady state observed peak plasma concentrations.
88- 130%) af peak- plasmakoncentrationerne i steady- state.
The primary active metabolites were present in tumour at concentrations averaging 160 ng/g tissue, which corresponded to an overall average of 113% (range 88-130%) of the observed steady state peak plasma concentrations.
95%.
Plasma protein binding is approximately 95%.
Erlotinib bindes til serumalbumin og alfa- 1 glykoproteinsyre (AAG).
Erlotinib binds to serum albumin and alpha-1 acid glycoprotein (AAG).
Der er identificeret tre hovedmetaboliske udskillelsesveje:
There are three main metabolic pathways identified:
1) O- demetylering af en eller begge sidekæder, efterfulgt af oxidering til carboxylsyre; 2) oxidering af acetylengruppen efterfulgt af hydrolyse til arylcarboxylsyre; og 3) aromatisk hydroxylering af phenyl- acetylengruppen.
1) O-demethylation of either side chain or both, followed by oxidation to the carboxylic acids; 2) oxidation of the acetylene moiety followed by hydrolysis to the aryl carboxylic acid; and 3) aromatic hydroxylation of the phenyl-acetylene moiety.