qanastek/EMEA-V3 huggingface dataset:
In the event of severe or persistent diarrhoea, nausea, anorexia, or vomiting associated with dehydration, Tarceva therapy should be interrupted and appropriate measures should be taken to treat the dehydration (see section 4.8).
F’ każ ta ’ dijarea qawwija jew persistenti, dardir, anoressija, jew remettar assoċjat ma ’ deidrazzjoni, kura b’ Tarceva trid titwaqqaf u miżuri xierqa jittieħdu għall- kura tad - deidrazzjoni (ara sezzjoni 4. 8).
There have been rare reports of hypokalaemia and renal failure (including fatalities).
Kien hemm rapporti rari ta ’ ipokalemja u insuffiċjenza renali (inkluż mwiet).
Some cases were secondary to severe dehydration due to diarrhoea, vomiting and/ or anorexia, while others were confounded by concomitant chemotherapy.
Uħud mill- każijiet kienu sekondarji għall- deidrazzjoni qawwija minħabba dijarea, rimettar u/ jew anoressija, filwaqt li oħrajn irriżultaw wkoll minħabba l- użu fl- istess ħin ta ’ kemjoterapija.
In more severe or persistent cases of diarrhoea, or cases leading to dehydration, particularly in groups of patients with aggravating risk factors (concomitant medications, symptoms or diseases or other predisposing conditions including advanced age), Tarceva therapy should be interrupted and appropriate measures should be taken to intensively rehydrate the patients intravenously.
F’ każijiet ta ’ dijarea aktar serja jew persistenti, jew każijiet li jwasslu għall - deidrazzjoni, speċjalment fi gruppi ta ’ pazjenti li għandhom fatturi ta ’ riskju li jaggravaw (mediċini li jittieħdu fl- istess waqt, sintomi jew mard jew kondizzjonijiet oħra li jippredisponu inkluż età avvanzata), kura b’ Tarceva trid titwaqqaf u miżuri xierqa għandhom jittieħdu sabiex il- pazjenti jiġu reidrati intensivament minn ġol- vini.
In addition, renal function and serum electrolytes including potassium should be monitored in patients at risk of dehydration.
Barra minn hekk, f’ pazjenti b’ riskju ta ’ deidrazzjoni, il- funzjoni renali u l- elettroliti fis- serum, inkluż il- potassju għandhom jiġu osservati wkoll.
Rare cases of hepatic failure (including fatalities) have been reported during use of Tarceva.
Każijiet rari ta ’ insuffiċjenza tal- fwied (inkluż imwiet) kienu rrappurtati waqt l- użu ta ’ Tarceva.
Confounding factors have included pre-existing liver disease or concomitant hepatotoxic medications.
Fatturi li jaggravaw inkludew mard tal- fwied eżistenti minn qabel jew l- użu fl- istess waqt ta ’ medikazzjonijiet epatotossiċi.
Therefore, in such patients, periodic liver function testing should be considered.
Għalhekk, f’ dawn il- pazjenti, għandu jiġi kkunsidrat ittestjar perjodiku tal- funzjoni tal - fwied.
Tarceva dosing should be interrupted if changes in liver function are severe (see section 4.8).
L- iddożar ta ’ Tarceva għandu jitwaqqaf jekk il- bidliet fil- funzjoni tal- fwied huma severi (ara sezzjoni 4. 8).
The tablets contain lactose and should not be administered to patients with rare hereditary problems of galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption.
Il- pilloli fihom lattosju u għalhekk m’ għandhomx jingħataw lill- pazjenti bi problemi ereditarji rari ta ’ intolleranza għall- galattosju, nuqqas ta ’ Lapp lactase jew tnaqqis ta ’ l- assorbiment ta ’ glukosju - gallatosju.
Erlotinib is characterised by a decrease in solubility at pH above 5.
Erlotinib huwa kkaratterizzat b’ nuqqas fis- solubilità f’ pH aktar minn 5.
Drugs that alter the pH of the upper GI tract, like proton pump inhibitors, H2 antagonists and antacids, may alter the solubility of erlotinib and hence its bioavailability.
Mediċini li jbiddlu l- pH tal - parti ta ’ fuq ta ’ l- apparat GI bħal inibituri tal- pompi tal- protoni, antagonisti ta ’ H2 u antaċidi, jistgħu jbiddlu s- solubilità ta ’ erlotinib u għalhekk il- biodisponibiltà tiegħu.
Increasing the dose of Tarceva when coadministered with such agents is not likely to compensate for the loss of exposure.
Żieda fid- doża ta ’ Tarceva meta mogħtija flimkien ma ’ dawn is- sustanzi x’ aktarx li ma tikkumpensax għan- nuqqas ta ’ espożizzjoni.
Combination of erlotinib with proton pump inhibitors should be avoided.
Taħlita ta ’ erlotinib ma ’ inibituri tal- pompi tal- protoni għandha tiġi evitata.
The effects of concomitant administration of erlotinib with H2 antagonists and antacids are unknown; however, reduced bioavailability is likely.
L- effetti ta ’ l- għotja ta ’ erlotinib flimkien ma ’ antagonisti ta ’ H2 u antaċidi mhumiex magħrufa; iżda, biodisponibiltà mnaqqsa hija probabbli.
Therefore, concomitant administration of these combinations should be avoided (see section 4.5).
Għalhekk l- għotja flimkien ta ’ dawn it- taħlitiet għandha tiġi evitata (ara sezzjoni 4. 5).
If the use of antacids is considered necessary during treatment with Tarceva, they should be taken at least 4 hours before or 2 hours after the daily dose of Tarceva.
Waqt kura b’ Tarceva, jekk l- użu ta ’ antaċidi huwa kkunsidrat bħala neċessarju, għandhom jittieħdu mill- anqas 4 sigħat qabel jew sagħtejn wara d- doża ta ’ kuljum ta ’ Tarceva.
Erlotinib is a potent inhibitor of CYP1A1, and a moderate inhibitor of CYP3A4 and CYP2C8, as well as a strong inhibitor of glucuronidation by UGT1A1 in vitro.
Elotinib huwa inibitur qawwi ta ’ CYP1A1, u inibitur moderat ta ’ CYP3A4 u CYP2C8, kif wkoll huwa inibitur b’ saħħtu ta ’ glukuronidazzjoni minn UGT1A1 in vitro.
The physiological relevance of the strong inhibition of CYP1A1 is unknown due to the very limited expression of CYP1A1 in human tissues.
Ir- rilevanza fiżjoloġika ta ’ l- inibizzjoni b’ saħħita ta ’ CYP1A1 mhix magħrufa minħabba d- dehra limitata ħafna ta ’ CYP1A1 fit- tessut uman.
When erlotinib was co-administered with ciprofloxacin, a moderate CYP1A2 inhibitor, the erlotinib exposure [AUC] increased significantly by 39%, while no statistically significant change in Cmax was found.
Meta erlotinib ingħata flimkien ma ’ ciprofloxacin, inibitur moderat ta ’ CYP1A2, l- espożizzjoni għal erlotinib [AUC] żdiedet b’ mod sinifikattiv b’ 39%, waqt li ma nstabet l- ebda bidla ta ’ sinifikanza
Similarly, the exposure to the active metabolite increased by about 60% and 48% for AUC and Cmax, respectively.
Bl- istess mod, l- espożizzjoni għall- metobolit attiv żdiedet b’ madwar 60% u 48% għall- AUC u Cmax, rispettivament.
The clinical relevance of this increase has not been established.
Ir- relevanza klinika ta ’ din iż- żieda ma ġietx stabbilita.
Caution should be exercised when ciprofloxacin or potent CYP1A2 inhibitors (e. g. fluvoxamine) are combined with erlotinib.
Għandu jkun hemm kawtela meta ciprofloxacin jew inibituri qawwija ta ’ CYP1A2 (e. ż. fluvoxamine) jitħaltu flimkien ma ’ erlotinib.
If adverse events related to erlotinib are observed, the dose of erlotinib may be reduced.
Jekk ikunu osservati avvennimenti avversi relatati ma ’ erlotinib, id- doża ta ’ erlotinib tista ’ titnaqqas.
In another clinical study, erlotinib was shown not to affect pharmacokinetics
Kura minn qabel jew għotja fl- istess ħin ta ’ tarceva ma bidlux it- tneħħija tas- substrati prototipiċi ta ’ CYP3A4, midazolam u erythromycin, iżda dehru li jnaqqsu il- biodisponibiltà orali ta ’ midazolam b’ sa 24%.
4 of the concomitantly administered CYP3A4/ 2C8 substrate paclitaxel.
Fi studju kliniku ieħor, erlotinib intwera li ma affettwax il- farmakokinetika ta ’ paclitaxel, susbtrat ta ’ CYP3A4/ 2C8, mogħti fl- istess ħin.
Significant interactions with the clearance of other CYP3A4 substrates are therefore unlikely.
Għalhekk, interazzjonijiet sinifikanti mat- tneħħija ta ’ substrati oħra ta ’ CYP3A4 huma improbabbli.
The inhibition of glucuronidation may cause interactions with medicinal products which are substrates of UGT1A1 and exclusively cleared by this pathway.
L- inibizzjoni ta ’ glukuronidazzjoni tista ’ tikkawża interazzjonijiet ma ’ prodotti mediċinali oħra li huma substrati ta ’ UGT1A1 u jitneħħew esklusivament permeżż ta ’ dan il- passaġġ.
Gilbert’ s disease) may exhibit increased serum concentrations of bilirubin and must be treated with caution.
Pazjenti b’ ammont żgħir ta ’ UGT1A1 jew mard ġenetiku ta ’ glukuronidazzjoni (e. ż. il- marda ta ’ Gilbert) jistgħu juru żieda tal- konċentrazzjoni fis- serum ta ’ bilirubina u jridu jiġu kkurati b’ attenzjoni.
Erlotinib is metabolised in the liver by the hepatic cytochromes in humans, primarily CYP3A4 and to a lesser extent by CYP1A2.
Erlotinib huwa metabolizzat mill- fwied permezz ta ’ ċitokromi tal- fwied fil- bniedem, prinċipalment minn CYP3A4 u ftit inqas minn CYP1A2.
Extrahepatic metabolism by CYP3A4 in intestine, CYP1A1 in lung, and CYP1B1 in tumour tissue also potentially contribute to the metabolic clearance of erlotinib.
Metaboliżmu mhux fil- fwied, minn CYP3A4 ġol- musrana, CYP1A1 fil- pulmun, u CYP1B1 fit- tessut tat- tumur ukoll jikkontribwixxu potenzjalment għat- tneħħija metabolika ta ’ erlotinib.
Potential interactions may occur with active substances which are metabolised by, or are inhibitors or inducers of, these enzymes.
Interazzjonijiet potenzjali jistgħu jseħħu ma ’ sustanzi attivi li jiġu metabolizzati minn, jew huma inibituri jew indutturi ta ’ dawn l- enżimi.
Potent inhibitors of CYP3A4 activity decrease erlotinib metabolism and increase erlotinib plasma concentrations.
Inibituri qawwija ta ’ l- attività ta ’ CYP3A4 inaqqsu l- metaboliżmu ta ’ erlotinib u jżidu il - konċentrazzjoni ta ’ erlotinib fil- plażma.
In a clinical study, the concomitant use of erlotinib with ketoconazole (200 mg orally twice daily for 5 days), a potent CYP3A4 inhibitor, resulted in an increase of erlotinib exposure (86% of AUC and 69% of Cmax).
Fi studju kliniku, l- użu ta ’ erlotinib flimkien ma ’ ketoconazole (200 mg mill- ħalq darbtejn kuljum għal ħamest ijiem), inibitur qawwi ta ’ CYP3A4, wassal għal żieda fl- espożizzjoni ta ’ erlotinib (86% ta ’ AUC u 69% ta ’ Cmax).
Therefore, caution should be used when erlotinib is combined with a potent CYP3A4 inhibitor, e. g. azole antifungals (i. e. ketoconazole, itraconazole, voriconazole), protease inhibitors, erythromycin or clarithromycin.
Għalhekk, l- użu ta ’ erlotinib flimkien ma ’ inibitur qawwi ta ’ CYP3A4 e. ż. azole antifungals (ketoconazole, itraconazole, voriconazole), inibituri tal- protease, erythromycin jew clarithromycin, trid issir b’ attenzjoni.
If necessary the dose of erlotinib should be reduced, particularly if toxicity is observed.
Jekk hemm bżonn id- doża ta ’ erlotinib trid titnaqqas, speċjalment jekk tiġi osservata tossiċità.
Potent inducers of CYP3A4 activity increase erlotinib metabolism and significantly decrease erlotinib plasma concentrations.
Indutturi potenti ta ’ l- attività ta ’ CYP3A4 iżidu l- metaboliżmu ta ’ erlotinib u sinnifikament inaqqsu l - konċetrazzjoni ta ’ erlotinib fil- plażma.
In a clinical study, the concomitant use of erlotinib and rifampicin (600 mg orally once daily for 7 days), a potent CYP3A4 inducer, resulted in a 69% decrease in the median erlotinib AUC.
Fi studju kliniku, l- użu ta ’ erlotinib flimkien ma ’ rifampicin (600 mg mill- ħalq darba kuljum għal sebat ijiem), induttur qawwi ta ’ CYP3A4, wassal għal tnaqqis ta ’ 69% fl- AUC medjan ta ’ erlotinib.
Co-administration of rifampicin with a single 450 mg dose of Tarceva resulted in a mean erlotinib exposure (AUC) of 57.5% of that after a single 150 mg Tarceva dose in the absence of rifampicin treatment.
L- għotja flimkien ta ’ rifampicin ma ’ doża waħda ta ’ 450 mg ta ’ Tarceva wassal għal espożizzjoni medja għal erlotinib (AUC) ta ’ 57. 5% ta ’ dik wara doża waħda ta ’ 150 mg ta ’ Tarceva fin- nuqqas ta ’ kura b’ rifampicin.
Co-administration of Tarceva with CYP3A4 inducers should therefore be avoided.
Għalhekk, l- għotja ta ’ Tarceva flimkien ma ’ indutturi ta ’ CYP3A4 għandha tiġi evitata.
For patients who require concomitant treatment with Tarceva and a potent CYP3A4 inducer such as rifampicin an increase in dose to 300 mg should be considered while their safety (including renal and liver functions and serum electrolytes) is closely monitored, and if well tolerated for more than 2 weeks, further increase to 450 mg could be considered with close safety monitoring.
Għall- pazjenti li jinħtieġu kura b’ Tarceva flimkien ma ’ induttur qawwi ta ’ CYP3A4 bħal rifampicin, għandha tiġi kkunsidrata żieda fid- doża għal 300 mg filwaqt li s- sigurtà tagħhom (inkluż il- funzjonijiet renali u tal- fwied u l- elektroliti fis- serum) tiġi sorveljata mill- viċin, u jekk ittollerat tajjeb għal aktar minn ġimagħtejn, aktar żieda sa 450 mg tista ’ tkun ikkunsidrata b’ sorveljanza tas- sigurtà mil- viċin.
Reduced exposure may also occur with other inducers e. g. phenytoin, carbamazepine, barbiturates or St.
Espożizzjoni mnaqqsa tistà tiġri wkoll b’ indutturi oħra e. ż. phenytoin, carbamazepine, barbiturates jew St.
Johns Wort (hypericum perforatum).
Johns Wort (hypericum perforatum).
Caution should be observed when these active substances are combined with erlotinib.
L- użu ta ’ dawn is- sustanzi attivi ma ’ erlotinib trid issir b’ attenzjoni.
Alternate treatments lacking potent CYP3A4 inducing activity should be considered when possible.
Kura alternattiva, mingħajr attività qawwija li tinduċi CYP3A4, trid tiġi kkunsidrata meta possibli.
International Normalized Ratio (INR) elevations, and bleeding events including gastrointestinal bleeding have been reported in clinical studies, some associated with concomitant warfarin administration (see section 4.8) and some with concomitant NSAID administration.
Żieda fl- International Normalized Ratio (INR), u episodji ta ’ fsada inkluż fsada gastro- intestinali ġew irrappurtati fi studji kliniċi, wħud assoċjati ma ’ l- għotja flimkien ta ’ warfarin (ara sezzjoni 4. 8) u wħud ma ’ l- għotja flimkien ta ’ NSAID.
Patients taking warfarin or other coumarin-derivative anticoagulants should be monitored regularly for changes in prothrombin time or INR.
Pazjenti li qed jieħdu warfarin jew anitkowagulaturi oħra ġejjin minn coumarin għandhom jiġu sorveljati regolarment għal tibdil fil- ħin prothrombin jew INR.
Results of a pharmacokinetic interaction study indicated a significant 2.8-, 1.5- and 9-fold reduced AUCinf, Cmax and plasma concentration at 24 hours, respectively, after administration of Tarceva in smokers as compared to non-smokers (see section 5.2).
Ir- riżultati ta ’ studju ta ’ interazzjoni farmakokinetika indikaw tnaqqis sinnifikanti ta ’ 2. 8 -, 1. 5 -, u 9 - drabi AUCinf, Cmax u konċenrazzjoni tal- plażma f’ 24 siegħa, rispettivament, wara l- għotja ta ’ Tarceva f’ pazjenti li jpejpu meta mqabbla ma ’ dawk li ma jpejpux (ara sezzjoni 5. 2).
Therefore, patients who are still smoking should be encouraged to stop smoking as early as possible before initiation of treatment with Tarceva, as plasma erlotinib concentrations are reduced otherwise.
L- effett
The clinical effect of the decreased exposure has not been formally assessed but it is likely to be clinically significant.
5 kliniku ta ’ tnaqqis fl- espożizzjoni għadu ma ġiex assessjat formalment iżda huwa probabbli li huwa klinikament sinnifikanti.
Erlotinib is a substrate for the P-glycoprotein active substance transporter.
Erlotinib huwa substrat tat- trasportatur tas- sustanza attiva ta ’ P- glycoprotein.
Concomitant administration of inhibitors of Pgp, e. g. cyclosporine and verapamil, may lead to altered distribution and/ or altered elimination of erlotinib.
L- ġħotja flimkien ta ’ inibituri ta ’ Pgp, e. ż. cyclosporine u verapamil, tista ’ twassal għal tibdil fid- distribuzzjoni u/ jew tibdil fl- eliminazzjoni ta ’ erlotinib.
CNS toxicity has not been established.
Il- konsegwenza ta ’ din l- interazzjoni e. ż. tossiċità tas- CNS, għadha ma ġietx stabbilita.
Caution should be exercised in such situations.
F’ dawn iċ- ċirkostanżi jrid ikun hemm kawtela.
Erlotinib is characterised by a decrease in solubility at pH above 5.
Erlotinib huwa kkaratterizzat minn tnaqqis fis- solubilità f’ pH ta ’ aktar minn 5.
Co-administration of
Mediċini li jbiddlu l - pH tal- parti ta ’ fuq tas- sistema gastro- intestinali jistgħu jbiddlu s- solubilità ta ’ erlotinib u b’ hekk il - bijodisponibiltà tiegħu.
5 erlotinib with omeprazole, a proton pump inhibitor (PPI), decreased the erlotinib exposure [AUC] and maximum concentration [Cmax] by 46% and 61%, respectively.
L- għotja flimkien ta ’ erlotinib ma ’ omeprazole, inibitur tal- pompi tal- protoni (PPI), naqqsu l- espożizzjoni għal erlotinib [AUC] u l- konċentrazzjoni massima [Cmax] b ’ 46% u 61%, rispettivament.
There was no change to Tmax or half-life.
Ma kien hemm l- ebda tibdil f’ Tmax jew fil- half- life.
Concomitant administration of Tarceva with 300 mg ranitidine, an H2-receptor antagonist, decreased erlotinib exposure [AUC] and maximum concentrations [Cmax] by 33% and 54%, respectively.
L- għoti ta ’ Tarceva flimkien ma ’ 300 mg ranitidine, antagonist tar- riċettur H2, jnaqqas l- espożizzjoni għal erlotinib [AUC] u l - konċentrazzjonijiet massimi [Cmax] bi 33% u 54%, rispettivament.
Increasing the dose of Tarceva when co-administered with such agents is not likely to compensate for this loss of exposure.
Żjieda fid- doża ta ’ Tarceva meta mogħti flimkien ma ’ sustanzi bħal dawn x’ aktarx li ma tikkompensax għal dan it- telf fl- espożizzjoni.
However, when Tarceva was dosed in a staggered manner 2 hours before or 10 hours after ranitidine 150 mg b. i. d., erlotinib exposure [AUC] and maximum concentrations [Cmax] decreased only by 15% and 17%, respectively.
Madankollu, meta Tarceva kien iddożat waħdu, sagħtejn qabel jew 10 sigħat wara ranitidine 150 mg b. i. d., l- espożizzjoni għal erlotinib [AUC] u l- konċentrazzjonijiet massimi [Cmax] naqsu biss bi 15% u 17%, rispettivament.
The effect of antacids on the absorption of erlotinib have not been investigated but absorption may be impaired, leading to lower plasma levels.
L- effett ta ’ antaċidi fuq l- assorbiment ta ’ erlotinib ma ġewx investiġati iżda l - assorbiment jista ’ jiġi mnaqqas, u b’ hekk iwassal għall- livelli aktar baxxi fil- plażma.
In summary, the combination of erlotinib with proton pump inhibitors should be avoided.
Bħala sommarju, it- taħlita ta ’ erlotinib ma ’ inbituri tal- pompi tal- protoni għandha tiġi evitata.
If the use of ranitidine is considered, it should be used in a staggered manner; i. e.
Jekk jiġi kkunsidrat l- użu ta ’ ranitidine, dan għandu jintuża waħdu; i. e.
Tarceva must be taken at least 2 hours before or 10 hours after ranitidine dosing.
Tarceva għandu jittieħed ta ’ l- inqas sagħtejn qabel jew 10 sigħat wara d- dożaġġ ta ’ ranitidine.
In a Phase Ib study, there were no significant effects of gemcitabine on the pharmacokinetics of erlotinib nor were there significant effects of erlotinib on the pharmacokinetics of gemcitabine.
Fi studju ta ’ fażi Ib, la kien hemm effetti sinifikanti ta ’ gemcitabine fuq il- farmakokinetika ta ’ erlotinib, u lanqas effetti sinifikanti ta ’ erlotinib fuq il- farmakokinetika ta ’ gemcitabine.
Erlotinib increases platinum concentrations.
Erlotinib iżid il- konċentrazzjonijiet ta ’ platinum.
In a clinical study, the concomitant use of erlotinib with carboplatin and paclitaxel led to an increase of total platinum AUC0-48 of 10.6%.
Fi studju kliniku, l- użu ta ’ erlotinib flimkien ma ’ carboplatin u paclitaxel wassal għal żieda ta ’ 10. 6% fl- AUC0- 48 totali ta ’ platinum.
Although statistically significant, the magnitude of this difference is not considered to be clinically relevant.
Għalkemm statistikament sinifikanti, il- kobor ta ’ din id- differenza mhux ikkunsidrat li huwa klinikament rilevanti.
In clinical practice, there may be other co-factors leading to an increased exposure to carboplatin like renal impairment.
Fil- prattika klinika, jista ’ jkun hemm ukoll fatturi oħra li jwasslu għal żieda fl- espożizzjoni għal carboplatin, bħal indeboliment renali.
There were no significant effects of carboplatin or paclitaxel on the pharmacokinetics of erlotinib.
Ma kien hemm l- ebda effetti sinifikanti ta ’ carboplatin jew paclitaxel fuq il- famakokinetika ta ’ erlotinib.
Capecitabine may increase erlotinib concentrations.
Capecitabine jista ’ jżid il- konċentrazzjonijiet ta ’ erlotinib.
When erlotinib was given in combination with capecitabine, there was a statistically significant increase in erlotinib AUC and a borderline increase in Cmax when compared with values observed in another study in which erlotinib was given as single agent.
Meta erlotinib ingħata flimkien ma ’ capecitabine, kien hemm żieda statistikament sinifikanti fl- AUC ta ’ erlotinib u żieda żgħira f’ Cmax meta mqabbel mal- valuri osservati fi studju ieħor fejn erlotinib ingħata bħala aġent waħdu.
There were no significant effects of erlotinib on the pharmacokinetics of capecitabine.
Ma kien hemm l- ebda effetti sinifikanti ta ’ erlotinib fuq il- farmakokinetika ta ’ capecitabine.
There are no studies in pregnant women using erlotinib.
Ma sarux studji b’ erlotinib f’ nisa tqal.
Studies in animals have shown some reproductive toxicity (see section 5.3).
Studji fuq l- animali urew xi tossiċitá fuq is- sistema riproduttiva (ara sezzjoni 5. 3).
The potential risk for humans is unknown.
Ir- riskju li jista ’ jkun hemm fuq in- nies mhux magħruf.
Women of childbearing potential must be advised to avoid pregnancy while on Tarceva.
Nisa li jistgħu joħorġu tqal għandhom jiġu avżati sabiex jevitaw tqala waqt kura b’ Tarceva.
Adequate contraceptive methods should be used during therapy, and for at least 2 weeks after completing therapy.
Għandhom jintużaw mezzi ta ’ kontraċezzjoni effettivi waqt il- kura, u għal ta ’ l- inqas ġimagħtejn wara li tintemm il- kura.
Treatment should only be continued in pregnant women if the potential benefit to the mother outweighs the risk to the foetus.
Il- kura f’ nisa tqal għandha titkompla biss jekk il- benefiċċju potenzjali għall- omm huwa akbar mir- riskji għall - fetu.
It is not known whether erlotinib is excreted in human milk.
Mhux magħruf jekk erlotinib jintremiex fil- ħalib uman.
Because of the potential harm to the infant, mothers should be advised against breastfeeding while receiving Tarceva.
Minħabba il- ħsara potenzjali lit- tarbija, l - ommijiet għandhom jiġu avżati biex ma jreddgħux waqt li qed jieħdu Tarceva.
No studies on the effects on the ability to drive and use machines have been performed; however erlotinib is not associated with impairment of mental ability.
Ma sarux studji dwar l- effetti fuq il- ħila biex issuq jew tħaddem magni; iżda erlotinib mhux assoċjat ma ’ tnaqqis fl- abilità mentali.
Non-small cell lung cancer (Tarceva administered as single agent in study BR.21):
Kanċer tal- pulmun mhux taċ- ċellola żgħira (Tarceva mgħoti waħdu fl- istudji BR. 21):
Rash (75%) and diarrhoea (54%) were the most commonly reported adverse drug reactions (ADRs).
Raxx (75%) u dijarea (54%) kienu l- aktar reazzjonijiet avversi tal- mediċina (ADRs) komuni li ġew irrapportati.
Most were Grade 1/ 2 in severity and manageable without intervention.
Ħafna kienu Grad 1/ 2 fis- severità u kienu kkontrollati mingħajr l- ebda intervent.
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.
Raxx u dijarea ta ’ Grad 3/ 4 seħħew f’ 9% u 6%, rispettivament tal- pazjenti kkurati b’ Tarceva u f’ kull każ kien hemm 1% tal- pazjenti li waqqfu l- istudju minħabba f’ dan.
Dose reduction for rash and diarrhoea was needed in 6% and 1% of patients, respectively.
Tnaqqis fid- doża minħabba raxx u dijarea kienet meħtieġa għal 6% u 1% tal- pazjenti, rispettivament.
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.
Fi studju BR. 21, il- ħin medjan sakemm deher ir- raxx kien ta ’ tmint ijiem, u il- ħin medjan sakemm deheret id- dijarrea kien ta ’ 12- il ġurnata.
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.
Effetti avversi li seħħew aktar ta ’ spiss (≥3%) f’ pazjenti kkurati b’ Tarceva milli dawk fil- grupp plaċebo fl- istudju pivotal BR. 21, u f’ minn ta ’ l- inqas 10% tal- pazjenti fil- grupp b’ Tarceva, huma miġbura skond il- Grad National Cancer Institute- Common Toxicity Criteria (NCI- CTC) f ’ Tabella 1.
Very common ADRs in study BR.21
ADRs komuni ħafna fl- istudju BR. 21
Placebo N = 242
Plaċebo N = 242
Grade Grade
Grad NCI- CTC
3
Kull Grad 3
Grade Grade
4 Kull Grad
MedDRA Preferred Term Total patients with any AE Infections and infestations
Terminu Ippreferut MedDRA Total ta ’ pazjenti b’ kull AE Infezzjonijiet u infestazzjonijiet
Infection* Metabolism and nutrition disorders
Infezzjoni * Disturbi fil- metaboliżmu u n - nutrizzjoni
Anorexia Eye disorders
Anoreksja Disturbi fl- għajnejn
Conjunctivitis Keratoconjunctivitis sicca Respiratory, thoracic and mediastinal disorders
Konġuntivite Keratokonġuntivite sikka Disturbi respiratorji, toraċiċi u medjastinali
Dyspnoea Cough Gastrointestinal disorders
Qtugħ ta ’ nifs
Rash*** Pruritus Dry skin General disorders and administration site conditions
Raxx *** Ħakk Ġilda xotta Disturbi ġenerali u kondizzjonijiet ta ’ mnejn jingħata
* Severe infections, with or without neutropenia, have included pneumonia, sepsis, and cellulitis. ** Can lead to dehydration, hypokalemia and renal failure. *** Rash included dermatitis acneiform.
7 * Infezzjonijiet severi, bi jew bla newtropenja, inkludew pnewmonja, sepsi u ċellulite. ** Tista ’ twassal għal deidrazzjoni, ipokalimja u insuffiċjenza renali. *** Raxx inkluda dermatite acneiform.
Pancreatic cancer (Tarceva administered concurrently with gemcitabine in study PA.3):
Kanċer tal- frixa (Tarceva mgħoti flimkien ma ’ gemcitabine fl- istudji PA. 3):
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.
Fl- istudju pivitali PA. 3, f’ pazjenti b’ kanċer tal- frixa li kienu qed jirċievu Tarceva 100 mg flimkien ma ’ gemcitabine, l- aktar reazzjonijiet avversi komuni kienu għeja, raxx u dijarea.
In the Tarceva plus gemcitabine arm, Grade 3/ 4 rash and diarrhoea were each reported in 5% of patients.
Fil- grupp ta ’ Tarceva flimkien ma ’ gemcitabine, raxx ta ’ Grad 3/ 4, u dijarea, kienu rrappurtati f’ 5% tal- pazjenti.
The median time to onset of rash and diarrhoea was 10 days and 15 days, respectively.
Il - ħin medjan sakemm deheru raxx u dijarrea kien ta ’ għaxart ijiem u ħmistax- il ġurnata rispettivament.
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.
Fi 2% tal- pazjenti, raxx u dijarrea t- tnejn irriżultaw fi tnaqqis fid- doża, u irriżultaw f’ waqfien ta ’ l - istudju f’ 1% tal- pazjenti li kienu qed jirċievu Tarceva flimkien ma ’ gemcitabine.
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.
Fl- istudju pivitali PA. 3, effetti avversi li seħħew aktar ta ’ spiss (≥3%) f’ pazjenti kkurati b’ Tarceva 100 mg flimkien ma ’ gemcitabine milli fil- grupp ikkurati bi plaċebo flimkien ma ’ gemcitabine, u li seħħew f’ minn ta ’ l- anqas 10% tal- pazjenti fil- grupp b’ Tarceva 100 mg flimkien ma ’ gemcitabine, huma miġbura skond il- Grad National Cancer Institute- Common Toxicity Criteria (NCI- CTC) f ’ Tabella 2.
Very common ADRs in study PA.3 (100 mg cohort)
ADRs komuni ħafna fl- istudju PA. 3 (100
Any
Kull
Placebo N = 256
Plaċebo N = 256
NCI-CTC
Grad NCI- CTC
MedDRA Preferred Term Total patients with any AE Infections and infestations
Terminu ppreferut MedDRA Total ta ’ pazjenti b’ kull AE Infezzjonijiet u infestazzjonijiet
Weight decreased Psychiatric disorders
Tnaqqis fil- piż Disturbi psikjatriċi
Depression Nervous system disorders
Depressjoni Disturbi fis- sistema nervusa
Headache Neuropathy Respiratory, thoracic and mediastinal disorders
Uġigħ ta ’ ras Newropatija Disturbi respiratoriu, toraċiċi u medjastinali
Cough Gastrointestinal disorders
Sogħla Disturbi gastro- intestinali
Diarrhoea** Stomatitis Dyspepsia Flatulence Skin and subcutaneous tissue disorders
Dijarea ** Stomatite Dispepsja Gass fl- istonku Disturbi fil- ġilda u fit- tessut ta ’ taħt il - ġilda
Rash*** Alopecia General disorders and administration site conditions
Raxx *** Alopeċja
Pyrexia Fatigue Rigors
Deni Għeja Tertir
* Severe infections, with or without neutropenia, have included pneumonia, sepsis, and cellulitis. ** Can lead to dehydration, hypokalemia and renal failure. *** Rash included dermatitis acneiform.
* Infezzjonijiet severi, bi jew bla newtropenja, inkludew pulmonite, sepsi, u ċellulite. ** Tista ’ twassal għal deidrazzjoni, ipokalimja u insuffiċjenza renali. *** Raxx inkluda dermatite acneiform.
Other Observations:
Osservazzjonijiet Oħra:
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:
Evalwazzjoni ta ’ sigurtà ta ’ Tarceva hija bbażàta fuq riżultati minn 759 pazjent ikkurat b’ ta ’ l- inqas doża waħda ta ’ 150 mg ta ’ Tarceva matul l- istudju NSCLC BR. 21 ta ’ Fażi III, studju NSCLC A248 - 1007 ta ’ Fażi II, u tliet studji ta ’ Fażi II f’ popolazzjonijiet oħra minbarra NSCLC:
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.
248- 101 (kanċer ta ’ l- ovarji), A248- 1003 (kanċer fir- ras jew l- għonq), u OSI2288g (kanċer metastatiku tas- sider) u l- 285 pazjent li ngħataw Tarceva 100 jew 150 mg flimkien ma ’ gemcitabine fl- istudju PA. 3 ta ’ fażi III b’ kanċer tal- frixa.
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.
Dawn it- termini li ġejjin qed jintużaw sabiex l- effetti mhux mixtieqa jitniżżlu skond il- frekwenza: komuni ħafna (> 1/ 10); komuni (> 1/ 100, < 1/ 10); mhux komuni (> 1/ 1000, < 1/ 100); Rari (> 1/ 10000, < 1/ 1000); rari ħafna (< 1/ 10, 000) inkluż rapporti iżolati.
The following adverse reactions have been observed in patients who received Tarceva administered as single agent and patients who received Tarceva concurrently with chemotherapy.
Ir- reazzjonijiet avversi li ġejjin kienu osservati f’ pazjenti li ngħataw Tarceva waħdu u f’ pazjenti li ngħataw Tarceva flimkien ma ’ kemjoterapija.
Very common ADR’ s are presented in Tables 1 and 2, ADR ’ s in other frequency categories are summarized below.
ADRs komuni ħafna huma ppreżentati f’ Tabelli 1 u 2, ADRs f’ kategoriji ta ’ frekwenzi oħra huma miġbura taħt.
Gastrointestinal disorders:
Disturbi Gastro- intestinali:
Gastrointestinal bleeding.
Fsada gastro- intestinali.
In clinical studies, some cases have been associated with concomitant warfarin administration (see section 4.5) and some with concomitant NSAID administration.
Fi studji kliniċi, uħud mill- każijiet ġew assoċjati ma ’ l- għotja fl- istess ħin ta ’ warfarin (ara sezzjoni 4. 5) u xi wħud ma ’ l - għotja fl- istess ħin ta ’ NSAID.
Common (in PA.3):
Komuni (f’ PA. 3):
Uncommon
Mhux komuni:
Alopecia.
Alopeċja.
Dry skin.
Ġilda xotta.
Paronychia.
Paronikja.
Hirsutism, eyelash/ eyebrow changes and brittle and loose nails.
Xagħar eċċessiv, tibdil fix- xagħar ta ’ l- għajnejn/ ħuġbejn u dwiefer fraġili u laxki.
Very common (in PA.3) Common (in BR.21):
Komuni ħafna (f’ PA. 3) Komuni (f’ BR. 21):
Liver function test abnormalities (including increased alanine aminotransferase [ALT], aspartate aminotransferase [AST], bilirubin).
Anormalità fit- test tal- funzjoni tal- fwied (inkluż żieda f’ alanine aminotransferase [ALT], aspartate aminotransferase [AST], bilirubina).
These were mainly mild or moderate in severity, transient in nature or associated with liver metastases.
Dawn kienu ħafna drabi ħfief jew modetati fis- severità, temporanji jew assoċjati ma ’ metastasi fil- fwied.
Rare cases of hepatic failure (including fatalities) have been reported during use of Tarceva.
Każijiet rari ta ’ insuffiċjenza renali (inkluż imwiet) ġew irrappurtati waqt l- użu ta ’ Tarceva.
Confounding factors have included pre-existing liver disease or concomitant hepatotoxic medications (see section 4.4).
Fatturi li aggravaw inkludew mard tal- fwied eżistenti minn qabel jew medikazzjonijiet epatotossiċi fl- istess ħin (ara sezzjoni 4. 4).
Eye disorders:
9 Disturbi fl- għajnejn:
Common:
Keratite.
Conjunctivitis in study PA.3.
Konġuntivite fi studju PA. 3.
Corneal ulcerations have been reported very rarely in patients receiving Tarceva as a complication of mucocutaneous inflammation.
Ulċeri tal- korneja kienu rrappurtati b’ mod rari ħafna bħala kumplikazzjoni ta ’ infjammazzjoni mukokutanja f’ pazjenti li qed jirċievu Tarceva.
Respiratory, thoracic and mediastinal disorders:
Disturbi respiratorji, toraċiċi u medjastinjali:
Serious interstitial lung disease (ILD), including fatalities, in patients receiving Tarceva for treatment of NSCLC or other advanced solid tumours (see section 4.4).
Epistassi Marda ta ’ l- interstizju tal- pulmun (ILD) serja, inkluż mwiet, f’ pazjenti li rċevew Tarceva bħala kura għal NSCLC jew tumuri solidi avvanzati oħra (ara sezzjoni 4. 4).
Single oral doses of Tarceva up to 1000 mg erlotinib in healthy subjects, and up to 1600 mg in cancer patients have been tolerated.
Dożi singoli mill- ħalq ta ’ Tarceva sa ’ 1000 mg ta ’ erlotinib f’ soġġetti f’ saħħithom, u sa ’ 1600 mg f’ pazjenti bil- kanċer kienu ttollerati.
Repeated twice daily doses of 200 mg in healthy subjects were poorly tolerated after only a few days of dosing.
Dożi ripetuti darbtejn kuljum ta ’ 200 mg f’ soġġetti f’ saħħithom kienu ttollerati ftit li xejn wara biss ftit ġranet ta ’ dożaġġ.
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.
Ibbażat fuq tgħarif minn dawn l- istudji, effetti avversi serji bħal dijarea, raxx u possibilment żieda fl- attività ta ’ aminotransferases tal- fwied jistgħu jseħħu b’ dożi aktar mid- doża rakkomandata.
In case of suspected overdose, Tarceva should be withheld and symptomatic treatment initiated.
F’ każ ta ’ suspett ta ’ doża eċċessiva, Tarceva għandu jitwaqqaf u tinbeda kura sintomatika.
Pharmacotherapeutic group: antineoplastic agent, ATC code:
Kategorija farmakoterapewtika: agent antinejoplastiku, Kodiċi ATC:
9 Erlotinib is an epidermal growth factor receptor/ human epidermal growth factor receptor type 1 (EGFR also known as HER1) tyrosine kinase inhibitor.
Erlotinib huwa riċettur tal- fattur ta ’ żvilupp epidermiku / inibitur tyrosine kinase tal- fattur ta ’ żvilupp epidermiku ta ’ tip 1 uman (EGFR magħruf ukoll bħala HER1).
Erlotinib potently inhibits the intracellular phosphorylation of EGFR.
Erlotinib jinibixxi b’ mod qawwi l - phosphorylation intraċellolari ta ’ EGFR.
EGFR is expressed on the cell surface of normal cells and cancer cells.
EGFR jidħer fil- wiċċ taċ- ċellola f’ ċelloli normali u ċelloli tal- kanċer.
In non-clinical models, inhibition of EGFR phosphotyrosine results in cell stasis and/ or death.
F’ mudelli mhux kliniċi, inibizzjoni ta ’ EGFR phosphotyrosine jirriżulta fi stasi ċellolari u/ jew mewt.
Non-small cell lung cancer (Tarceva administered as single agent in study BR.21):
Kanċer tal- pulmun mhux taċ- ċellola żgħira (Tarceva mogħti waħdu fi studju BR. 21):
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.
L- effikaċja u s- sigurtà ta ’ Tarceva intweriet fi prova randomised, double- blind u kkontrollata bil - plaċebo (BR. 21), f’ 731 pazjent b’ NSCLC lokalment avvanzat jew li mmetastatizza wara falliment ta ’ minn ta ’ l- inqas kors wieħed ta ’ kemjoterapija.
Patients were randomised 2:1 to receive Tarceva 150 mg or placebo orally once daily.
L- pazjenti kienu magħżula bl- addoċċ 2: 1 biex jingħataw Tarceva 150 mg jew plaċebo mill- ħalq darba kuljum.
Study endpoints included overall survival, progression-free survival (PFS), response rate, duration of response, time to deterioration of lung cancer-related symptoms (cough, dyspnoea and pain), and safety.
L- miri ta ’ l- istudju inkludew sopravivenza totali, sopravivenza mingħajr żvilupp (PFS), rata ta ’ rispons, tul tar- rispons, żmien sakemm is- sintomi relatati mal- kanċer tal- pulmun (sogħla, qtugħ ta ’ nifs u uġigħ) jiddeterjoraw, u sikurtà.
The primary endpoint was survival.
L- mira Primarja kienet sopravivenza.
Demographic characteristics were well balanced between the two treatment groups.
Karatteristiċi demografiċi kienu bbilanċjati tajjeb bejn iż- żewġ gruppi ta ’ kura.
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.
Madwar tnejn minn kull tliet pazjenti kienu rġiel u madwar terz kellhom linja bażi ta ’ ECOG performance status (PS) ta ’ 2, u 9% kellhom linja bażi ECOG PS ta ’ 3.
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.
Tlieta u disgħin fil- mija u 92% tal- pazjenti kollha fil- gruppi b’ Tarceva u plaċebo, rispettivament, kienu rċevew minn qabel kors li kien fih platinum u 36% u 37% tal- pazjenti kollha, rispettivament, ingħataw kura minn qabel b’ taxane.
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).
Il- hazard ratio (HR) aġġustat għall- imwiet fil- grupp b ’ Tarceva relattiv għall- grupp plaċebo kien ta ’ 0. 73 (95% CI, 0. 60 sa 0. 87) (p = 0. 001).
The percent of patients alive at 12 months was 31.2% and 21.5%, for the Tarceva and placebo groups, respectively.
Il- persentaġġ ta ’ pazjenti ħajjin wara 12- il xhar kien ta ’ 31. 2% u 21. 5%, fil- gruppi ta ’ Tarceva u tal- plaċebo, rispettivament.
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).
Is- sopravivenza totali medjana kienet ta ’ 6. 7 xhur fil- grupp b’ Tarceva (95% CI, 5. 5 sa ’ 7. 8 xhur) meta mqabbel ma ’ 4. 7 xhur fil- grupp bil - plaċebo (95% CI, 4. 1 sa ’ 6. 3 xhur).
The effect on overall survival was explored across different patient subsets.
10 L- effett fuq is- sopravivenza totali ġie studjat f’ subsets differenti ta ’ pazjenti.
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).
L- effett ta ’ Tarceva fuq is- sopravivenza totali kienet simili f’ pazjenti b’ linja bażi tal- performance status (ECOG) ta ’ 2- 3 (HR = 0. 77, CI 0. 6- 1. 0) jew 0- 1 (HR = 0. 73, 0. 6- 0. 9), rġiel (HR = 0. 76, CI 0. 6- 0. 9) jew pazjenti nisa (HR = 0. 80, CI 0. 6- 1. 1), pazjenti b’ eta ’ < 65 sena (HR = 0. 75, CI 0. 6- 0. 9) jew pazjenti ixjaħ (HR = 0. 79, CI 0. 6- 1. 0), pazjenti li ħadu kors minn qabel (HR = 0. 76, CI 0. 6- 1. 0) jew ħadu aktar minn kors wieħed minn qabel (HR = 0. 75, CI 0. 6- 1. 0), Kawkasu (HR = 0. 79, CI 0. 6- 1. 0) jew pazjenti Asjatiċi (HR = 0. 61, 0. 4- 1. 0), pazjenti b’ adenokarċinoma (HR = 0. 71, CI 0. 6- 0. 9) jew karċinoma squamous cell (HR = 0. 67, CI 0. 5- 0. 9), iżda mhux f’ pazjenti b’ istoloġijiet oħra (HR 1. 04, CI 0. 7- 1. 5), pazjenti b’ marda f’ stadju IV fil- ħin tad- dijanjosi (HR = 0. 92, CI 0. 7- 1. 2) jew b ’ marda < stadju IV fil - ħin tad- dijanjosi (HR = 0. 65, 0. 5- 0. 8).
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).
Pazjenti li qatt ma pejpu ħadu ħafna aktar benefiċċju minn erlotinib (sopravivenza HR = 0. 42, CI 0. 28- 0. 64) meta mqabbla ma ’ pazjenti li qed ipejpu jew kienu jpejpu (HR = 0. 87, CI 0. 71- 1. 05).
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).
F’ 45% tal- pazjenti li kien mgħaruf l- istat ta ’ espressjoni ta ’ EGFR, il- hazard ratio kien ta ’ 0. 68 (CI 0. 49- 0. 94) għall- pazjenti li kellhom tumuri posittivi għal EGFR u 0. 93 (CI 0. 63- 1. 36) għall- pazjenti b ’ tumuri negattivi għal EGFR (iddefiniti minn IHC bl- użu ta ’ kitt EGFR pharmDx u b’ EGFR- negattiv iddefinit bħala anqas minn 10% taċ- ċelloli tat- tumur jieħdu l- kulur).
In the remaining 55% of patients with unknown EGFR-expression status, the hazard ratio was 0.77 (CI 0.61-0.98).
Fil- 55% tal- pazjenti li fadal, bi stat mhux mgħaruf ta ’ espressjoni ta ’ EGFR, il- hazard ratio kien ta ’ 0. 77 (CI 0. 61- 0. 98).
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).
Il- PFS medjan kien ta ’ 9. 7 ġimgħat fil- grupp ta ’ Tarceva (95% CI, 8. 4 sa ’ 12. 4 ġimgħat) meta mqabbel ma ’ 8. 0 ġimgħat fil- grupp plaċebo (95% CI, 7. 9 sa ’ 8. 1 ġimgħat).
The objective response rate by RECIST in the Tarceva group was 8.9% (95% CI, 6.4 to 12.0).
Ir- rata ta ’ rispons oġġettiv minn RECIST fil- grupp ta ’ Tarceva kien ta ’ 8. 9% (95% CI, 6. 4 to 12. 0).
The first 330 patients were centrally assessed (response rate 6.2%); 401 patients were investigator- assessed (response rate 11.2%).
L- ewwel 330 pazjent kienu evalwati ċentralment (rata ta ’ rispons 6. 2%); 401 pazjent kienu evalwati minn investigatur (rata ta ’ rispons 11. 2%).
The median duration of response was 34.3 weeks, ranging from 9.7 to 57.6+ weeks.
It- tul medjan ta ’ rispons kienet ta ’ 34. 3 ġimgħat, u jvarja minn 9. 7 sa ’ 57. 6+ ġimgħat.
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).
Il- proporzjon ta ’ pazjenti li kellhom rispons komplut, rispons parzjali jew marda stabbli kien ta ’ 44. 0% u 27. 5%, rispettivament, għall- gruppi ta ’ Tarceva u plaċebo (p=0. 004).
10 A survival benefit of Tarceva was also observed in patients who did not achieve an objective tumour response (by RECIST).
Benefiċċju ta ’ sopravivenza ta ’ Tarceva ġie osservat ukoll f’ pazjenti li ma laħqux l- iskop ta ’ rispons mit- tumur (minn RECIST).
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.
Dan kien evidenza minn hazard ratio għall- mewt ta ’ 0. 82 (95% CI, 0. 68 sa 0. 99) fost pazjenti li kellhom bħala l- aħjar rispons marda stabbli jew marda progressiva.
Tarceva resulted in symptom benefits by significantly prolonging time to deterioration in cough, dyspnoea and pain, versus placebo.
Tarceva wassal għall- benefiċċji fis- sintomi billi jtawwall sinnifikament it- tul sakemm is- sogħla, qtugħ ta ’ nifs u uġigħ jiddeterjoraw, kontra l- plaċebo.
Pancreatic cancer (Tarceva administered concurrently with gemcitabine in study PA.3):
Kanċer tal- frixa (Tarceva mogħti flimkien ma ’ gemcitabine fi studju PA. 3):
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.
L- effikaċja u s- sigurtà ta ’ Tarceva flimkien ma ’ gemcitabine bħala l- kura preferita kienu studjati fi prova randomised, double- blind u kkontrollata bil- plaċebo f’ pazjenti b’ kanċer tal- frixa lokalment avvanzat, li ma jistgħax jitneħħa kirurġikament, jew li mmetastatizza.
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]).
L- pazjenti kienu magħżula bl - addoċċ biex jingħataw Tarceva jew plaċebo darba kuljum fuq skeda kontinwa flimkien ma ’ gemcitabine IV (1000 mg/ m2, Ċiklu 1 - Ġranet 1, 8, 15, 22, 29, 36 u 43 ta ’ ċiklu ta ’ 8 ġimgħat; Ċiklu 2 u ċikli ta ’ wara - Ġranet 1, 8 u 15 ta ’ ċiklu ta ’ 4 ġimgħat [doża u skeda approvata għall- kanċer tal - frixa, ara l- SPC ta ’ gemcitabine]).
Tarceva or placebo was taken orally once daily until disease progression or unacceptable toxicity.
Tarceva jew plaċebo kien meħud mill- ħalq darba kuljum sal - proggressjoni tal- marda jew sakemm it- tossiċità ma kienetx aċċettabli aktar.
The primary endpoint was overall survival.
Il- mira primarja kienet sopravivenza totali.
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:
Il- linja bażi tal- karatteristiċi demografiċi u tal- marda tal- pazjenti kienu simili bejn iż- żewġ gruppi ta ’ kura, ta ’ Tarceva flimkien ma ’ gemcitabine jew plaċebo flimkien ma ’ gemcitabine, għajr għal proporzjon kemmxejn akbar ta ’ nisa fil- grupp ta ’ erlotinib/ gemcitabine meta mqabbel mal- grupp plaċebo/ gemcitabine:
Baseline Females Baseline ECOG performance status (PS) = 0 Baseline ECOG performance status (PS) = 1 Baseline ECOG performance status (PS) = 2 Metastatic disease at baseline
11 Linja bażi Nisa Linja bażi ta ’ ECOG performance status (PS) = 0 Linja bażi ta ’ ECOG performance status (PS) = 1 Linja bażi ta ’ ECOG performance status (PS) = 2 Marda metastatika f’ linja bażi
Placebo
Plaċebo 44% 32% 51% 17% 76%
CI of
CI ta ’ Δ
(months)
Tarceva Plaċebo
(months) (months) Overall Population
HR
CI of Δ
CI ta ’
HR HR
Valur- P
value
(xhur)
Median overall survival
(xhur) (xhur) Popolazzjoni Totali
6.4
HR
6.0
6. 4 8. 8
0.41
6. 0 7. 6
-0.54-1.64
0. 41 1. 16
Mean overall survival
0. 69- 0. 98
1.16
0. 028
Metastatic Population Median overall survival
Popolazzjoni b’ marda Metastatika Sopravivenza totali medjana
-0.26-1.56
- 0. 26- 1. 56
0.66-0.98
0. 66- 0. 98
0.029
0. 17- 2. 66
Locally Advanced Population Median overall survival
Popolazzjoni b’ marda Avvanzata Lokalment Sopravivenza totali medjana
0.93
0. 36
0.65-1.35
- 2. 43- 2. 96
0.713
0. 93
Mean overall survival
0. 65- 1. 35
10.7
0. 713
10.5
Sopravivenza totali medja
0.19
10. 7
-2.43-2.69
10. 5
0.9
0. 19
0.8
- 2. 43- 2. 69
Survival Probability
Sopravivenza Totali – Pazjenti Kollha 10 0. 9 Probabbiltà ta ’ Sopravivenza
HR = 0.82 (95% CI:
0. 8 HR = 0. 82 0. 7 (95% CI:
Placebo + gemcitabine (n = 260) Median OS = 6.0 months
Placebo + gemcitabine (n = 260) OS medjan = 6. 4 xhur
Median OS = 6.4 months
OS medjan = 6. 4 xhur
Overall Survival – Patients with Distant Metastases 1.0
12 Sopravivenza Totali – Pazjenti b’ Metastasi Distanti 1. 0
Survival Probability
0. 9 Probabbiltà ta ’ Sopravivenza
HR = 0.80 (95% CI:
0. 8 HR = 0. 80 0. 7 (95% CI:
Median OS = 5.93 months
OS medjan = 5. 93 xhur
0.1 gemcitabine (n = 197) Median OS = 5.0 6 months 0.0
gemcitabine OS medjan =
6
6 12