qanastek/EMEA-V3 huggingface dataset:
If a suspected reaction is not manageable with dose delays, then temsirolimus may be reduced by 5 mg/ week decrements.
Jekk reazzjoni ssuspettata ma tkunx tista ’ tiġi mmaniġġjata bl- ittardjar tad- doża, allura temsirolimus jista ’ jitnaqqas b’ dekrementi ta ’ 5 mg/ ġimgħa.
Paediatric patients Experience in paediatric patients is limited.
Pazjenti pedjatriċi L- esperjenza f’ pazjenti pedjatriċi hi limitata.
The safety and effectiveness in paediatric patients have not been established.
Is- sigurtà u l- effettività f’ pazjenti pedjatriċi ma kinitx stabbilita.
Therefore, the use of TORISEL in the paediatric population is not recommended until further information on effectiveness and safety is available.
Għalhekk, l- użu ta ’ TORISEL fil- popolazzjoni pedjatrika mhuwiex rakkomandat sakemm informazzjoni addizzjonali dwar l- effettività u s- sigurtà tkun disponibbli.
Elderly patients No specific dose adjustment is necessary.
Pazjenti anzjani L- ebda aġġustament speċifiku fid- doża m’ hu meħtieġ.
Renal impairment No dose adjustment of temsirolimus is recommended in patients with renal impairment.
Indeboliment renali L- ebda aġġustament ta ’ TORISEL m’ hu rakkomandat f’ pazjenti b’ indeboliment renali.
Temsirolimus should be used with caution in patients with severe renal impairment (see section 4.4).
Temsirolimus għandu jintuża b’ attenzjoni f’ pazjenti b’ indeboliment sever renali (ara sezzjoni 4. 4).
Hepatic impairment Temsirolimus should be used with caution in patients with hepatic impairment.
Indeboliment tal- fwied Temsirolimus għandu jintuża b’ attenzjoni f’ pazjenti b’ indeboliment tal- fwied.
Use of temsirolimus in patients with severe hepatic impairment is not recommended (see section 4.4).
L- użu ta ’ temsirolimus f’ pazjenti b’ indeboliment serju tal- fwied m’ huwiex rakkomandat (ara sezzjoni 4. 4).
Hypersensitivity to temsirolimus, its metabolites (including sirolimus), polysorbate 80, or to any of the excipients of TORISEL.
Sensittività eċċessiva għal temsirolimus, il- metaboliti tiegħu (li jinkludu sirolimus), polysorbate 80, jew għal xi sustanzi mhux attivi ta ’ TORISEL.
Paediatrics Temsirolimus is not recommended for use in paediatric patients due to insufficient data on safety.
Pazjenti pedjatriċi Temsirolimus m’ huwiex rakkomandat għall- użu f’ pazjenti pedjatriċi minħabba li m’ hemmx tagħrif biżżejjed dwar is- sigurtà.
Elderly Based on the results of a phase 3 study, elderly patients may be more likely to experience certain adverse reactions, including oedema and pneumonia.
Anzjani Ibbażat fuq ir- riżultati ta ’ studju ta ’ fażi 3, il- pazjenti anzjani jista ’ jkun li jkunu aktar suxxettibbli għal ċerti avvenimenti avversi li jinkludu edema u pnewmonja.
TORISEL has not been studied in patients undergoing haemodialysis.
Indeboliment renali It- tneħħija ta ’ temsirolimus mill- kliewi hi negliġibbli; ma sarux studji f’ pazjenti b’ indeboliment renali li jvarja (ara sezzjoni 4. 2 u 5. 2) TORISEL ma kienx studjat f’ pazjenti li jkunu fuq l- emodijalisi.
3 Hepatic impairment Temsirolimus is cleared predominantly by the liver.
Indeboliment tal- fwied Temsirolimus jitneħħa l- biċċa l- kbira mill- fwied.
No data are currently available regarding the influence of hepatic dysfunction and/ or hepatic metastases on temsirolimus disposition (see section 4.2).
Bħalissa m’ hemm l- ebda informazzjoni disponibbli dwar l- influwenza ta ’ disfunzjoni epatika u/ jew ta ’ metastasi epatika fuq id- dispożizzjoni ta ’ temsirolimus (ara sezzjoni 4. 2).
Intracerebral bleeding Patients with central nervous system (CNS) tumours (primary CNS tumours or metastases) and/ or receiving anticoagulation therapy may be at an increased risk of developing intracerebral bleeding (including fatal outcomes) while receiving therapy with temsirolimus.
Ħruġ ta ’ demm intraċerebrali Pazjenti b’ tumuri tas- sistema nervuża ċentrali (CNS) (tumuri primarji tas- CNS jew metastasi) u/ jew li jkunu qed jirċievu terapija ta ’ kontra l- koagulazzjoni, jistgħu jkunu f’ riskju miżjud li jiżviluppaw ħruġ ta ’ demm intraċerebrali (li jinkludi riżultati fatali) waqt li jkunu qed jirċievu terapija b’ temsirolimus.
Renal failure Renal failure (including fatal outcomes) has been observed in patients receiving TORISEL for advanced renal cell cancer and/ or with pre-existing renal insufficiency (see section 4.8).
3 Insuffiċjenza renali L- insuffiċjenza renali (li tinkludi riżultati fatali) kienet osservata f’ pazjenti li kienu qed jirċievu TORISEL għal kanċer avvanzat taċ- ċelluli renali u/ jew għal insuffiċjenza tal- kliewi li kienet teżisti minn qabel (ara sezzjoni 4. 8).
Cataracts Cataracts have been observed in some patients who received the combination of temsirolimus and interferon-α.
Katarretti Il- katarretti kienu osservati f’ xi pazjenti li rċivew il- kumbinazzjoni ta ’ temsirolimus u interferon- α.
Hypersensitivity/ infusion reactions Hypersensitivity/ infusion reactions (including some life-threatening and rare fatal reactions), including and not limited to flushing, chest pain, dyspnoea, hypotension, apnoea, loss of consciousness, hypersensitivity and anaphylaxis, have been associated with the administration of temsirolimus (see section 4.8).
Sensittività eċċessiva/ infużjoni Reazzjonijiet ta ’ sensittività eċċessiva/ għall- infużjoni (li jinkludu xi reazzjonijiet li huma ta ’ periklu għall- ħajja u reazzjonijiet fatali rari), li jinkludu u li mhumiex limitati għal fwawar, uġigħ fis- sider, qtugħ ta ’ nifs, pressjoni baxxa, apneja, tintilef minn sensik, sensittività eċċessiva u anafilassi, kienu assoċjati mal- għoti ta ’ temsirolimus (ara sezzjoni 4. 8).
These reactions can occur very early in the first infusion, but may also occur with subsequent infusions.
Dawn ir- reazzjonijiet jistgħu jseħħu kmieni ħafna fl- ewwel infużjoni, iżda jistgħu jseħħu wkoll b’ infużjonijiet sussegwenti.
Patients should be monitored early during the infusion and appropriate supportive care should be available.
Il- pazjenti għandhom ikunu mmonitorjati kmieni matul l- infużjoni u kura adattata ta ’ appoġġ għandha tkun disponibbli.
Temsirolimus infusion should be interrupted in all patients with severe infusion reactions and appropriate medical therapy administered.
L - infużjoni b’ temsirolimus għandha titwaqqaf fil- pazjenti kollha li jkollhom reazzjonijiet severi għall - infużjoni u tingħata terapija medika adattata.
A benefit-risk assessment should be done prior to the continuation of temsirolimus therapy in patients with severe or life-threatening reactions.
Għandha ssir evalwazzjoni dwar il- benefiċċju- riskju qabel it- tkomplija tat- terapija b’ temsirolimus f’ pazjenti li jkollhom reazzjonijiet severi jew ta ’ periklu għall- ħajja.
If a patient develops a hypersensitivity reaction during the TORISEL infusion, despite the premedication, the infusion must be stopped and the patient observed for at least 30 to 60 minutes (depending on the severity of the reaction).
Jekk pazjent jiżviluppa reazzjoni ta ’ sensittività eċċessiva matul l- infużjoni ta ’ TORISEL, minkejja l - premedikazzjoni, l- infużjoni għandha titwaqqaf, u l- pazjent għandu jkun osservat għal mill- anqas 30 sa 60 minuta (skond is- severità tar- reazzjoni).
At the discretion of the physician, treatment may be resumed after the administration of an H1-receptor antagonist (diphenhydramine or similar antihistamine) and a H2-receptor antagonist (intravenous famotidine 20 mg or intravenous ranitidine 50 mg) approximately 30 minutes before restarting the TORISEL infusion.
Fid- diskrezzjoni tat- tabib, il- kura tista ’ titkompla wara l- għoti ta ’ antagonist ta ’ riċettur H1 (diphenhydramine jew antistamina simili) u antagonist ta ’ riċettur H2 (20 mg famotidine ġol- vini jew 50 mg ranitidine ġol- vini) madwar 30 minuta qabel ma tibda mill - ġdid l- infużjoni b’ TORISEL.
Administration of corticosteroids may be considered; however, the efficacy of corticosteroid treatment in this setting has not been established.
L- għoti ta ’ kortikosterojdi jista ’ jkun ikkunsidrat; madankollu, l - effikaċja tal- kura bil- kortikosterojdi f’ dan l- ambjent ma kinitx stabbilita.
The infusion may then be resumed at a slower rate (up to 60 minutes) and should be completed within six hours from the time that TORISEL is first added to sodium chloride 9 mg/ ml (0.9%) solution for injection.
L- infużjoni tista ’ mbagħad titkompla b’ rata inqas mgħaġġla (sa 60 minuta) u għandha titlesta fi żmien sitt sigħat mill- ħin li TORISEL ikun żdied għall- ewwel darba ma ’ soluzzjoni ta ’ 9 mg/ ml (0. 9%) sodium chloride għall - injezzjoni.
Because it is recommended that an H1 antihistamine be administered to patients before the start of the intravenous temsirolimus infusion, temsirolimus should be used with caution in patients with known hypersensitivity to the antihistamine or in patients who cannot receive the antihistamine for other medical reasons.
Minħabba li hu rakkomandat li tingħata antistamina H1 lil pazjenti qabel il- bidu tal- infużjoni ta ’ temsirolimus ġol- vini, temsirolimus għandu jintuża bl- attenzjoni f’ pazjenti b’ sensittività eċċessiva magħrufa għall- antistamina, jew f’ pazjenti li ma jistgħux jirċievu l- antistamina għal raġunijiet mediċi oħrajn.
Hypersensitivity reactions, including anaphylactic/ anaphylactoid reactions, angioedema, exfoliative dermatitis and hypersensitivity vasculitis, have been associated with the oral administration of sirolimus.
Reazzjonijiet ta ’ sensittività eċċessiva, li jinkludu reazzjonijiet anafilattiċi/ anafilattojdi, - anġjodema, dermatite bil- qxur u vaskulite minħabba sensittività eċċessiva, kienu assoċjati ma ’ l- għoti orali ta ’ sirolimus.
Hyperglycaemia/ glucose intolerance/ diabetes mellitus Patients should be advised that treatment with TORISEL may be associated with an increase in blood glucose levels in diabetic and non-diabetic patients.
Ipergliċemija/ intolleranza għal glucose/ dijabete mellitus Il- pazjenti għandhom jingħataw parir li l- kura b’ TORISEL tista ’ tkun assoċjata ma ’ żieda fil- livelli tal- glucose fid- demm f’ pazjenti dijabetiċi u mhux dijabetiċi.
In a clinical trial, 26% of patients reported hyperglycaemia as an adverse event.
Fi prova klinika, 26% tal- pazjenti rrappurtaw l- iperġliċemija bħala avveniment avvers.
This may result in the need for an increase in the dose of, or initiation of, insulin and/ or hypoglycaemic agent therapy.
Dan jista ’ jirriżulta fil- ħtieġa ta ’ żieda fid- doża ta ’, jew il- bidu ta ’, insulina u/ jew terapija b’ mediċina ipoglikemika.
Patients should be advised to report excessive thirst or any increase in the volume or frequency of urination.
Il- pazjenti għandhom jingħataw parir biex jirrappurtaw għatx eċċessiv jew żieda fil- volum jew fil- frekwenza meta jagħmlu l- awrina.
4 Infections Patients may be immunosuppressed and should be carefully observed for the occurrence of infections, including opportunistic infections.
Infezzjonijiet Il- pazjenti jistgħu jkunu immunosuppressati u għandhom jkunu osservati bl- attenzjoni għall - okkorrenza ta ’ infezzjonijiet, li jinkludu infezzjonijiet opportunistiċi.
Interstitial lung disease There have been cases of non-specific interstitial pneumonitis, including rare fatal reports, occurring in patients who received weekly intravenous TORISEL.
Xi pazjenti kienu
Some patients were asymptomatic with pneumonitis detected on computed tomography scan or chest radiograph.
4 asintomatiċi, bil- pnewmonite li kienet osservata fuq computed tomography scan jew radjografija tas - sider.
Others presented with symptoms such as dyspnoea, cough, and fever.
Pazjenti oħrajn kellhom sintomi bħal qtugħ ta ’ nifs, sogħla, u deni.
Some patients required discontinuation of TORISEL or treatment with corticosteroids and/ or antibiotics, while some patients continued treatment without additional intervention.
Xi pazjenti kellhom bżonn it - twaqqif ta ’ TORISEL jew tal- kura bil- kortikosterojdi u/ jew antibijotiċi, filwaqt li xi pazjenti komplew il- kura mingħajr interventi addizzjonali.
Patients should be followed for clinical respiratory symptoms.
Il- pazjenti għandhom ikunu segwiti għal sintomi respiratorji kliniċi.
Hyperlipaemia The use of TORISEL in renal cell carcinoma patients was associated with increases in serum triglycerides and cholesterol.
Iperlipemija L- użu ta ’ TORISEL f’ pazjenti b’ karċinoma taċ- ċelluli renali kien assoċjat ma ’ żidiet fit- triglycerides u l- kolesterol fis- serum.
In a clinical trial, hyperlipaemia was reported as an adverse event in 27% of patients.
Fi prova klinika, l- iperlipemija kienet irrappurtata bħala avveniment avvers f’ 27% tal- pazjenti.
This may require initiation, or increase, in the dose of lipid-lowering agents.
Dan jista ’ jkun jeħtieġ il- bidu, jew żieda, fid- doża ta ’ mediċini li jbaxxu l- lipidi.
Serum cholesterol and triglycerides should be tested before and during treatment with TORISEL.
Il - kolesterol fis- serum u t- triglycerides għandhom ikunu ttestjati qabel u matul il- kura b’ TORISEL.
Wound healing complications The use of TORISEL has been associated with abnormal wound healing; therefore, caution should be exercised with the use of TORISEL in the peri-surgical period.
Kumplikazzjonijiet fil- fejqan tal- feriti L- użu ta ’ TORISEL kien assoċjat ma ’ fejqan anormali tal- feriti; għalhekk, għandha tingħata attenzjoni bl- użu ta ’ TORISEL fil- perijodu ta ’ qabel l- operazzjoni.
Concomitant use of angiotensin-converting enzyme (ACE) inhibitors Angioneurotic oedema-type reactions (including delayed reactions occurring two months following initiation of therapy) have been observed in some patients who received temsirolimus and ACE inhibitors concomitantly (see section 4.5).
L- użu fl- istess ħin ta ’ inibituri ta ’ enzima li tibdel angiotensin (angiotensin- converting enzyme - ACE) Reazzjonijiet anġjonewrotiċi bħal dawk ta ’ l- edema (li jinkludu reazzjonijiet li jseħħu wara ċertu żmien u li f’ dan il- każ jseħħu wara xahrejn wara l- bidu tat- terapija) kienu osservati f’ xi pazjenti li rċivew temsirolimus u inibituri ta ’ ACE fl- istess ħin (ara sezzjoni 4. 5).
Agents inducing CYP3A metabolism Agents such as carbemazepine, phenobarbital, phenytoin, rifampicin, rifabutin, rifapentine, and St.
Sustanzi li jikkaġunaw il- metaboliżmu CYP3A Mediċini bħal carbemazepine, phenobarbital, phenytoin, rifampicin, rifabutin, rifapentine u St.
John’ s Wort are strong inducers of CYP3A4/ 5 and may decrease composite exposure of the active moieties, temsirolimus and its metabolite, sirolimus.
John’ s Wort huma inducers qawwija ta ’ CYP3A4/ 5 u jistgħu jnaqqsu espożizzjoni tal- kompost tal- moieties attivi, ta ’ temsirolimus u tal- metabolit tiegħu, sirolimus.
Therefore, continuous administration beyond 5-7 days with agents that have CYP3A4/ 5 induction potential should be avoided.
Għalhekk, l- għoti kontinwa lilhemm minn 5- 7 ijiem b’ mediċini li għandhom potenzjal li jinduċu CYP3A4/ 5, għandu jkun evitat.
Agents inhibiting CYP3A metabolism Agents such as protease inhibitors (indinavir, nelfinavir, ritonavir), antifungals (e. g., itraconazole, ketoconazole, voriconazole), calcium channel blockers (e. g., diltiazem, verapamil), macrolide antibiotics (e. g., clarithromycin, erythromycin), and cimetidine, grapefruit juice, aprepitant, fluvoxamine and nefazodone are strong CYP3A4 inhibitors and may increase blood concentrations of the active moieties, temsirolimus and its metabolite, sirolimus.
Mediċini li jinibixxu l- metaboliżmu ta ’ CYP3A Mediċini bħal inibituri tal- protease (indinavir, nelfinavir, ritonavir), antifungali (eż., itraconazole, ketoconazole, voriconazole), calcium channel blockers (eż. diltiazem, verapamil), antibijotiċi macrolide (eż. clarithromycin, erythromycin), u cimetidine, meraq tal- grejpfrut, aprepitant, fluvoxamine u nefazodone huma inibituri qawwija ta ’ CYP3A4 u jistgħu jżidu l- konċentrazzjonijiet fid- demm tal- moieties attivi, temsirolimus u l- metabolit tiegħu, sirolimus.
Therefore, concomitant treatment with agents that have strong CYP3A4 inhibition potential should be avoided.
Għalhekk, il- kura fl- istess ħin b’ mediċini li għandhom potenzjal qawwi li jinibixxu CYP3A4, għandha tkun evitata.
Concomitant treatment with agents that have moderate CYP3A4 inhibition potential should be carried out with caution (see section 4.5).
Il- kura fl - istess ħin b’ mediċini li għandhom inibizzjoni moderata ta ’ CYP3A4 għandha ssir bl- attenzjoni (ara sezzjoni 4. 5).
Alternative treatments with agents that do not have CYP3A4 inhibition potential should be considered.
Kuri alternattivi b’ mediċini li ma jkollhomx potenzjal ta ’ inibizzjoni ta ’ CYP3A4 għandhom ikunu kkunsidrati.
Vaccinations Immunosuppressants may affect responses to vaccination.
Tilqim L- immunosuppressanti jistgħu jaffettwaw ir- risponsi għat- tilqima.
During treatment with TORISEL, vaccination may be less effective.
Matul il- kura b’ TORISEL, it - tilqima tista ’ tkun inqas effettiva.
The use of live vaccines should be avoided during treatment with TORISEL.
L- użu ta ’ tilqim ħaj għandu jkun evitat matul il- kura b’ TORISEL.
Examples of live vaccines are: measles, mumps, rubella, oral polio, BCG, yellow fever, varicella, and TY21a typhoid vaccines.
Eżempji ta ’ tilqim ħaj huma: ħosba, gattone, ħosba Ġermaniża, polio orali, BCG, yellow fever, ġidri r - riħ, u tilqim tat- tifojde TY21a.
Excipients This medicinal product (concentrate-diluent mixture) contains 35% volume ethanol (alcohol); i. e., up to 693.5 mg per dose, equivalent to 17.6 ml beer, 7.3 ml wine per dose.
Sustanzi mhux attivi Dan il- prodott mediċinali (taħlita ta ’ konċentrat- dilwent) fih 35% ta ’ ethanol (alkoħol) skond il- volum; i. e., sa 693. 5 mg f’ kull doża, ekwivalenti għal 17. 6 ml ta ’ birra, 7. 3 ml ta ’ nbid f’ kull doża.
5 Harmful for those suffering from alcoholism.
Dan hu ta ’ ħsara għal dawk li jbatu mill- alkoħoliżmu.
To be taken into account in pregnant or breast-feeding women, children and high-risk groups, such as patients with liver disease or epilepsy.
Dan għandu jkun ikkunsidrat f’ nisa tqal jew f’ dawk li qed ireddgħu, fi tfal u gruppi li qegħdin f’ riskju għoli, bħal pazjenti b’ mard tal- fwied jew li għandhom epilessija.
Concomitant use of angiotensin-converting enzyme (ACE) inhibitors Angioneurotic oedema-type reactions (including delayed reactions occurring two months following initiation of therapy) have been observed in some patients who received temsirolimus and ACE inhibitors concomitantly (see section 4.4).
L- użu fl- istess ħin ta ’ inibituri ta ’ enzima li tibdel angiotensin (angiotensin- converting enzyme - ACE) Reazzjonijiet anġjonewrotiċi tat- tip tal- edema (li jinkludu reazzjonijiet li jseħħu wara ċertu żmien li jseħħu wara xahrejn wara l- bidu tat- terapija) kienu osservati f’ xi pazjenti li rċivew temsirolimus u inibituri ACE fl- istess ħin (ara sezzjoni 4. 4).
Agents inducing CYP3A metabolism Co-administration of TORISEL with rifampicin, a potent CYP3A4/ 5 inducer, had no significant effect on temsirolimus Cmax (maximum concentration) and AUC (area under the concentration vs. time curve) after intravenous administration, but decreased sirolimus Cmax by 65% and AUC by 56%, compared to TORISEL treatment alone.
Sustanzi li jikkaġunaw il- metaboliżmu CYP3A L- għoti flimkien ta ’ TORISEL ma ’ rifampicin, inducer qawwi ta ’ CYP3A4/ 5, ma kellu l- ebda effett sinifikanti fuq is- Cmax ta ’ temsirolimus (konċentrazzjoni massima) u l- AUC (iż- żona taħt il - konċentrazzjoni vs. kurva tal- ħin) wara l- għoti ġol- vini, iżda naqqas is- Cmax ta ’ sirolimus b’ 65% u l - AUC b’ 56%, meta mqabbel mal- kura ta ’ TORISEL waħidha.
Therefore, concomitant treatment with agents that have CYP3A4/ 5 induction potential should be avoided (see section 4.4).
Għalhekk, il- kura fl- istess ħin b’ mediċini li għandhom potenzjal li jinduċu CYP3A4/ 5, għandha tkun evitata (ara sezzjoni 4. 4).
Agents inhibiting CYP3A metabolism Co-administration of TORISEL 5 mg with ketoconazole, a potent CYP3A4 inhibitor, had no significant effect on temsirolimus Cmax or AUC; however, sirolimus AUC increased 3.1-fold, and AUCsum (temsirolimus + sirolimus) increased 2.3-fold compared to TORISEL alone.
Mediċini li jinibixxu l- metaboliżmu ta ’ CYP3A L- għoti flimkien ta ’ TORISEL 5 mg ma ’ ketoconazole, inibitur qawwi ta ’ CYP3A4, ma kellu l- ebda effett sinifikanti fuq is- Cmax jew l- AUC ta ’ temsirolimus; madankollu, l- AUC ta ’ sirolimus żdied bi 3. 1 darbiet, u l- AUCsum (temsirolimus + sirolimus) żdied bi 2. 3 darbiet meta mqabbel ma ’ TORISEL waħdu.
The effect on the unbound concentrations of sirolimus has not been determined, but is expected to be larger than the effect on whole- blood concentrations due to the saturable binding to red blood cells.
L- effett fuq il- konċentrazzjonijiet mhux imwaħħla ta ’ sirolimus ma kienx stabbilit, iżda hu mistenni li jkun akbar mill- effett fuq il- konċentrazzjonijiet tad- demm sħiħ (whole- blood) minħabba t - twaħħil saturabbli maċ- ċelluli ħomor tad- demm.
The effect may also be more pronounced at a 25 mg dose.
L- effett jista ’ jkun ukoll aktar prominenti f’ doża ta ’ 25 mg.
Substances that are potent inhibitors of CYP3A4 activity (e. g., protease inhibitors, anti-fungals, macrolide antibiotics, nefazodone, selective serotonin re-uptake inhibitors) increase sirolimus blood concentrations.
Sustanzi li huma inibituri qawwija ta ’ l- attività ta ’ CYP3A4 (eż., inibituri tal- protease, anti - fungali, antibijotiċi macrolide, nefazodone, inibituri selettivi re- uptake ta ’ serotonin) iżidu l - konċentrazzjonijiet ta ’ sirolimus fid- demm.
Concomitant treatment of TORISEL with agents that have strong CYP3A4 inhibition potential should be avoided (see section 4.4).
Il- kura fl- istess ħin ta ’ TORISEL ma ’ mediċini li jkollhom potenzjal ta ’ inibizzjoni qawwija għal CYP3A4, għandha tkun evitata (ara sezzjoni 4. 4).
Concomitant treatment with moderate CYP3A4 inhibitors should only be made with caution.
Il- kura fl - istess ħin b’ inibituri moderati ta ’ CYP3A4 għandha ssir biss b’ attenzjoni.
Interaction with medicinal products metabolized by CYP2D6 In 23 healthy subjects, the concentration of desipramine, a CYP2D6 substrate, was unaffected when 25 mg of temsirolimus was co-administered.
Interazzjoni ma ’ prodotti mediċinali metabolati minn CYP2D6 Fi 23 pazjent b’ saħħtu, il- konċentrazzjoni ta ’ desipramine, sottostrat ta ’ CYP2D6, ma kinitx affettwata meta 25 mg ta ’ temsirolimus ingħata miegħu.
No clinically significant effect is anticipated when TORISEL is co-administered with agents that are metabolised by CYP2D6.
L- ebda effett klinikament sinifikanti m’ hu antiċipat meta TORISEL jingħata flimkien ma ’ mediċini li jkunu metabolati minn CYP2D6.
Interactions with drugs that are P-glycoprotein substrates In an in vitro study, temsirolimus inhibited the transport of P-glycoprotein substrates with an IC50 value of 2 µM.
Interazzjonijiet ma ’ mediċini li jkunu substrati ta ’ glikoproteina P Fi studju in vitro temsirolimus inibixxa t- trasport tas- substrati ta ’ glikoproteina P b’ valur IC50 ta ’ 2 µM.
The clinical relevance of this finding is not known.
Ir- rilevanza klinika ta ’ din is- sejba mhijiex magħrufa.
Amphiphilic agents Temsirolimus has been associated with phospholipidosis in rats.
Sustanzi amfifiliċi Temsirolimus kien assoċjat ma ’ fosfolipidosi fil- firien.
Phospholipidosis has not been observed in mice or monkeys treated with temsirolimus, nor has it been documented in patients treated with temsirolimus.
Il- fosfolipidosi ma kinitx osservata fil- ġrieden jew fix- xadini li kienu kkurati b’ temsirolimus, u lanqas ma kienet dokumentata f’ pazjenti kkurati b’ temsirolimus.
Although phospholipidosis has not been shown to be a risk for patients administered temsirolimus, it is possible that combined administration of temsirolimus with other amphiphilic agents such as amiodarone or statins could result in an increased risk of amphiphilic pulmonary toxicity.
Għalkemm ma ntweriex li l- fosfolipidosi hi ta ’ riskju għal pazjenti li jingħataw temsirolimus, hu possibbli li l- għoti flimkien ta ’ temsirolimus ma ’ sustanzi amfifiliċi oħrajn bħal amiodarone jew statins, jista ’ jirriżulta f’ żieda fir- riskju ta ’ tossiċità pulmonari amfifilika.
There are no adequate data from the use of temsirolimus in pregnant women.
M’ hemmx tagħrif biżżejjed dwar l- użu ta ’ temsirolimus f’ nisa tqal.
Studies in animals have shown reproductive toxicity.
Studji fuq l- annimali wrew tossiċità riproduttiva.
In reproduction studies in animals, temsirolimus caused embryo/ foetotoxicity
Fi studji dwar ir- riproduzzjoni fl- annimali, temsirolimus ikkawża embriju/ fetotossiċità li ntweriet bħala mortalità u tnaqqis fil- piżijiet tal- fetu (assoċjata ma ’ dewmien fl - ossifikazzjoni skeletrika) fil- firien u fil- fniek.
6 that was manifested as mortality and reduced foetal weights (with associated delays in skeletal ossification) in rats and rabbits.
irġiel, it- tnaqqis fil- fertilità u tnaqqis parzjalment riversibbli fl- għadd ta ’ l- isperma,
Teratogenic effects (omphalocele) were seen in rabbits.
kienu rrappurtati (ara sezzjoni 5. 3).
The potential risk for humans is unknown.
6 Mhux magħruf ir- riskju potenzjali fuq in- nies.
TORISEL must not be used during pregnancy, unless the risk for the embryo is justified by the expected benefit for the mother.
TORISEL ma jridx jintuża waqt it- tqala, ħlief jekk ir - riskju għall- embriju jkun ġustifikat mill- benefiċċju mistenni għall- omm.
Due to the unknown risk related to potential exposure during early pregnancy, women of childbearing potential must be advised not to become pregnant while using TORISEL.
Minħabba r- riskju mhux magħruf relatat ma ’ espożizzjoni potenzjali matul l- ewwel żmien tat- tqala, nisa li jista ’ jkollhom it- tfal iridu jingħataw parir biex ma joħorġux tqal meta jkunu qed jużaw TORISEL.
Men with partners of childbearing potential should use medically acceptable contraception while receiving TORISEL (see section 5.3).
Irġiel li għandhom is- sieħba tagħhom li jista ’ jkollha t- tfal, għandhom jużaw kontraċezzjoni li hi medikament aċċettabbli waqt li jkunu qed jirċievu TORISEL (are sezzjoni 5. 3).
It is unknown whether temsirolimus is excreted in human breast milk.
Mhux magħruf jekk temsirolimus jitneħħiex fil- ħalib tas- sider uman.
The excretion of temsirolimus in milk has not been studied in animals.
It- tneħħija ta ’ temsirolimus fil - ħalib ma ġietx studjata fl- annimali.
However, sirolimus, the main metabolite of temsirolimus, is excreted in milk of lactating rats.
Madankollu, sirolimus, il- metabolit ewlieni ta ’ temsirolimus, jitneħħa fil- ħalib ta ’ firien li jkunu jreddgħu.
Because of the potential for adverse reactions in breast-fed infants from temsirolimus, breast-feeding should be discontinued during therapy.
Minħabba l- potenzjal għal reazzjonijiet avversi minn temsirolimus fi trabi li jkunu qed jerdgħu, it- treddigħ għandu jitwaqqaf matul il- kura.
A total of 626 patients were randomly assigned in a phase 3, three-arm, randomised, open-label study of Interferon alfa (IFN-α) alone, TORISEL alone, and TORISEL and IFN-α.
Total ta ’ 626 pazjent kienu assenjati b’ mod każwali fi studju ta ’ Fażi 3, li kien three- arm, randomised u open- label ta ’ Interferon alfa (IFN- α) waħdu, TORISEL waħdu, u TORISEL u IFN- α.
A total of 616 patients received treatment:
Total ta ’ 616 pazjent irċivew il- kura:
200 patients received IFN-α weekly; 208 received TORISEL 25 mg weekly and 208 patients received a combination of IFN-α and TORISEL weekly.
200 pazjent irċivew IFN- α kull ġimgħa; 208 rċivew TORISEL 25 mg kull ġimgħa u 208 pazjent irċivew kumbinazzjoni ta ’ IFN- α u TORISEL kull ġimgħa.
Based on the results of the phase 3 study, elderly patients may be more likely to experience certain adverse reactions, including face oedema and pneumonia.
Fuq bażi tar- riżultati ta ’ l- istudju ta ’ fażi 3, il- pazjenti anzjani jista ’ jkun li jkunu aktar suxxettibbli għal ċerti reazzjonijiet li jinkludu edema tal- wiċċ u pnewmonja.
The most serious reactions observed with TORISEL are hypersensitivity/ infusion reactions (including some life-threatening and rare fatal reactions), hyperglycaemia/ glucose intolerance, infections, interstitial lung disease, hyperlipaemia, intracerebral bleeding, renal failure, bowel perforation, and wound healing complication.
L- aktar reazzjonijiet serji osservati b’ TORISEL huma reazzjonijiet ta ’ sensittività eċċessiva/ għall - infużjoni (li jinkludu xi reazzjonijiet li huma ta ’ periklu għall- ħajja u reazzjonijiet fatali rari), ipergliċemija/ intolleranza għal glucose, infezzjonijiet, mard interstizjali tal- pulmuni, iperlipemija, ħruġ ta ’ demm intraċerebrali, insuffiċjenza renali, perforazzjoni fl- imsaren, u kumplikazzjoniet fil- fejqan tal- feriti.
The most common (≥ 30%) adverse reactions (all grades) observed with TORISEL include anaemia, nausea, rash (including rash, pruritic rash, maculopapular rash, pustular rash), anorexia, oedema (including facial oedema and peripheral oedema), and asthenia.
L- aktar reazzjonijiet avversi komuni (≥30%) (il- gradi kollha) osservati b’ TORISEL jinkludu anemija, nawseja, raxx (li jinkludi raxx, raxx pruritiku, raxx makulopapulari bl- infafet, raxx bil- ponot), anoreksja, edema (li tinkludi edema tal- wiċċ u edema periferali), u astenja.
Cataracts have been observed in some patients who received the combination of temsirolimus and interferon-α.
Il- katarretti kienu osservati f' xi pazjent li rċivew il- kumbinazzjoni ta 'temsirolimus u interferon- α.
See section 4.4 for additional information concerning serious adverse reactions, including appropriate actions to be taken if specific reactions occur.
Ara sezzjoni 4. 4 għal informazzjoni addizzjonali dwar reazzjonijiet avversi serji, li tinkludi azzjonijiet xierqa li jridu jittieħdu jekk iseħħu reazzjonijiet speċifiċi.
The following list contains adverse reactions seen in clinical trial (Study 1).
Il- lista li ġejja fiha r- reazzjonijiet avversi li kienu osservati fil- prova klinika (Studju 1).
Only events for which there is at least reasonable suspicion of a causal relationship to intravenous treatment with TORISEL are listed.
Huma msemmijin biss dawk l- avvenimenti li għalihom hemm mill- inqas suspett raġonevoli ta ’ relazzjoni kawżali għall- kura ġol- vini b’ TORISEL.
Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.
F’ kull sezzjoni ta ’ frekwenza, l- effetti mhux mixtieqa huma mniżżla skond is- serjetà ta ’ tagħhom bl - aktar serji jitniżżlu l- ewwel.
Very common: ≥ 1/ 10
Ir- reazzjonijiet avversi huma elenkati skond il- kategoriji li ġejjin:
7 Common: ≥ 1/ 100 to < 1/ 10 Uncommon: ≥ 1/ 1,000 to < 1/ 100
Komuni ħafna: ≥1/ 10 Komuni: ≥1/ 100 sa < 1/ 10 Mhux Komuni: ≥1/ 1000 sa < 1/ 100
Adverse reactions in clinical trial 1
7 Reazzjonijiet avversi fi prova klinika 1
All
Il- Gradi
Grades n (%)
Kollha n (%)
3 & 4 n (%)
3u4 n (%)
Very common Common Common
Komuni ħafna Komuni Komuni
Blood creatinine increased Increased aspartate aminotransferase Increased alanine aminotransferase
Żieda fil- krejatinina tad- demm Żieda f' aspartate aminotransferase Żieda f' alanine aminotransferase
Blood and lymphatic system disorders
Disturbi tad- demm u
Thrombocytopaenia
Trombocitopenja
Anaemia Neutropaenia Leucopoenia Lymphopaenia
Anemija Newtropenja Lewkopenja Limfopenija
Very common
Komuni ħafna Komuni Mhux Komuni
Ageusia Intracerebral bleeding
Indeboliment fis- sens tat- togħma Telf tas- sens tat- togħma, Ħruġ ta 'demm intraċerebrali
Conjunctivitis (including lacrimation disorders)
Konġuntivite (li tinkludi disturbi tal - lakrimazzjoni)
Pericardial effusion (including haemodynamically significant pericardial effusions requiring intervention)
Ħruġ ta ’ likwidu mill- perikardju (li jinkludi ħruġ emodinamikament sinifikanti ta ’ likwidu mill- perikardju li jkun jeħtieġ intervent)
8 Adverse reactions in clinical trial 1
Disturbi respiratorji, toraċiċi u medjastinali
Very common
Komuni ħafna Komuni ħafna Komuni ħafna Komuni
Dyspnoea
Dispnea Tinfaraġ Sogħla Pnewmonite (li tinkludi pnewmonite fatali)
mediastinal disorders
(ara sezzjoni 4. 4)
Pleural effusion
Ħruġ ta ’ likwidu mill- plewra
Very common Very common Very common Very common Common Common Common Common Uncommon
Komuni ħafna Komuni ħafna Komuni ħafna Komuni ħafna Komuni ħafna Komuni Komuni Komuni Komuni Mhux Komuni
Vomiting Stomatitis Diarrhoea Nausea Abdominal distension Oral pain Gingivitis Aphthous stomatitis Bowel perforation
Uġigħ ta ’ żaqq Rimettar Stomatite Dijarea Nawseja Nefħa taż- żaqq Uġigħ fil- ħalq Ġinġivite Stomatite aphthous Perforazzjoni fl- imsaren
Renal and urinary disorders
Disturbi fil- kliewi u fis- sistema urinarja Disturbi fil- ġilda u fit -
Renal failure [including fatal outcomes] (see section 4.4)
Insuffiċjenza renali (li tinkludi riżultati fatali) (ara sezzjoni 4. 4)
Skin and subcutaneous tissue disorders
tessuti ta 'taħt il- ġilda
Rash (including rash, pruritic rash, maculopapular rash, pustular rash)
Raxx (li jinkludi raxx, raxx pruritiku, raxx makulopapulari, raxx bil- ponot)
Very common Very common Very common Very common Common
Komuni ħafna Komuni ħafna Komuni ħafna Komuni ħafna Komuni
Pruritus Acne Nail disorder Dry skin Exfoliative Dermatitis
Ħakk tal- ġilda Akne Mard tad- dwiefer Ġilda xotta Dermatite bil- Qxur
Musculoskeletal, and connective tissue disorders
connective tissue
Metabolism and nutrition disorders
Disturbi fil - metaboliżmu u n - nutrizzjoni:
Very common
Komuni ħafna Komuni ħafna Komuni ħafna Komuni ħafna
Hypokalaemia
Ipokalemija Ipergliċemija/ dijabete mellitus * Iperkolesterolemija Iperlipemija
20 (10)
20 (10) 53 (26) 51 (24) 57 (27)
7 (3)
7 (3) 22 (11) 1 (1) 8 (4)
Very common
Il- Gradi
Hyperglycaemia/ diabetes mellitus*
Sistema tal- Klassi ta ’ l- Organi
53 (26)
Frekwenza
22 (11)
3u4 n (%)
Very common Very common Very common
Komuni ħafna
Hypercholesterolaemia Hyperlipaemia Anorexia
Anoreksja
Hypophosphataemia
Ipofosfatemija
9 Adverse reactions in clinical trial 1
Infezzjonijiet u Impestazzjonijiet
Bacterial and viral infections (including infection, cellulitis, herpes zoster, herpes simplex, bronchitis, abscess)
Infezzjonijiet batterjali u virali (li jinkludu infezzjoni, ċellulite, herpes zoster, herpes simplex, bronkite, axxess)
Urinary tract infection (including dysuria, haematuria, cystitis, urinary frequency, urinary tract infection)
Infezzjoni fl- apparat urinarju (li tinkludi wġigħ u diffikultà biex tagħmel l- awrina, ematurja, ċistite, frekwenza urinarja, infezzjoni fl- apparat urinarju)
Very common Very common Common Common Common
Komuni ħafna Komuni ħafna Komuni Komuni Komuni
Pharyngitis Rhinitis Pneumonia Upper respiratory tract infection Folliculitis
Farinġite Rinite Pnewmonja Infezzjoni ta 'l- apparat respiratorju ta ’ fuq Follikulite
Venous thromboembolism (including deep vein thrombosis, pulmonary embolus)
Tromboemboliżmu venuż (li jinkludi trombożi profonda tal- vini u emboliżmu pulmonari)
Hypertension Thrombophlebitis
Pressjoni għolja Tromboflebite
Very common Very common Very common
Komuni ħafna Komuni ħafna Komuni ħafna Komuni ħafna
Pain Chest pain Oedema (including oedema, facial oedema, peripheral oedema)
Mukożite Uġigħ Uġigħ fis- sider Edema (li tinkludi edema, edema tal- wiċċ, edema periferali)
Very common Common
Komuni ħafna Komuni ħafna Komuni
Asthenia Impaired wound healing
Deni Astenja Indeboliment fil- fejqan tal- ferita
Allergic/ hypersensitivity reactions
Reazzjonijiet/ allerġiċi/ minħabba sensittività eċċessiva
*Patients should be advised that treatment with TORISEL may be associated with an increase in blood glucose levels in diabetic and non-diabetic patients.
* Il- pazjenti għandhom jingħataw parir li l- kura b’ TORISEL tista ’ tkun assoċjata ma ’ żieda fil- livelli tal- glucose fid- demm f’ pazjenti dijabetiċi u mhux dijabetiċi.
There is no specific treatment for TORISEL intravenous overdose.
M’ hemm l- ebda kura speċifika għal doża eċċessiva ta ’ TORISEL ġol- vini.
TORISEL has been safely administered to patients with renal cancer with repeated intravenous doses of temsirolimus as high as 220 mg/ m2.
TORISEL kien mogħti b’ mod sikur lil pazjenti b’ kanċer renali b’ dożi ripetuti ġol- vini ta ’ temsirolimus li kienu għoljin sa 220 mg/ m2.
L01X E09 10 Temsirolimus is a selective inhibitor of mTOR (mammalian target of rapamycin).
Temsirolimus hu inibitur selettiv ta ’ mTOR (mira mammifera ta ’ rapamycin).
Temsirolimus binds to an intracellular protein (FKBP-12), and the protein-temsirolimus complex binds and inhibits the activity of mTOR that controls cell division.
Temsirolimus jeħel ma ’ proteina intraċellulari (FKBP- 12), u l- kumpless proteina- temsirolimus jeħel u jinibixxi l- attività ta ’ mTOR li tikkontrolla d- diviżjoni taċ- ċelluli.
Inhibition of mTOR activity results in a G1 growth arrest in treated tumour cells resulting from selective disruption of translation of cell cycle regulatory proteins, such as D-type cyclins, c-myc, and ornithine decarboxylase.
L- inibizzjoni ta ’ l- attività mTOR tirriżulta fi twaqqif tat - tkabbir G1 fiċ- ċelluli tat- tumur li jkunu kkurati, li jirriżulta mill- interruzzjoni selettiva tal- bdil tal - proteini regulatorji taċ- ċiklu taċ- ċelluli, bħal cyclins ta ’ tip D, c- myc, u ornithine decarboxylase.
Temsirolimus exerts its effect by binding in a complex with FKBP-12 and mTOR.
Meta mTOR jeħel
When mTOR is bound in this complex, its ability to phosphorylate, and thereby control the activity of protein translation factors (4E-BP1 and S6K, both downstream of mTOR in the P13 kinase/ AKT pathway) that control cell division, is blocked.
9 f’ dan il- kumpless, il- ħila tiegħu li jagħmel phosphorylate, u b’ hekk jikkontrolla l- attività tal- fatturi tal - bdil tal- proteina (4E- BP1 u S6K, it- tnejn li huma downstream ta ’ mTOR fil- passaġġ P13 kinase/ AKT) li jikkontrollaw id- diviżjoni taċ- ċelluli, tkun imblukkata.
In addition to regulating cell cycle proteins, mTOR can regulate translation of the hypoxia-inducible factors, HIF-1 and HIF-2 alpha.
Minbarra li jirregola l- proteini taċ- ċiklu taċ- ċelluli, mTOR jista ’ jirregola l- bidla tal- fatturi hypoxia - inducible, HIF- 1 u HIF- 2 alpha.
These transcription factors regulate the ability of tumours to adapt to hypoxic microenvironments and to produce the angiogenic factor vascular endothelial growth factor (VEGF).
Dawn il- fatturi tat- traskrizzjoni jirregolaw il- ħila tat- tumuri biex jadattaw għal mikro- ambjenti ipossiċi u biex jipproduċu l- fattur anġjoġeniku, il- fattur tat- tkabbir endoteljali vaskulari (vascular endothelial growth factor - VEGF).
The anti-tumour effect of temsirolimus, therefore, may also in part stem from its ability to depress levels of HIF and VEGF in the tumour or tumour microenvironment, thereby impairing vessel development.
L- effett ta ’ kontra t- tumur ta ’ temsirolimus, għalhekk, jista ’ wkoll jirriżulta parzjalment mill- ħila tiegħu li jnaqqas il- livelli ta ’ HIF u VEGF fit- tumur jew fil- mikro- ambjent tat- tumur, u b’ hekk itellef l- iżvilupp tal- vini.
Clinical Efficacy The safety and efficacy of TORISEL in the treatment of advanced renal cell carcinoma (RCC) were studied in the following two randomised clinical trials:
Effikaċja Klinika Is- sigurtà u l- effikaċja ta ’ TORISEL fil- kura ta ’ karċinoma avvanzata taċ- ċelluli renali (RCC), kienu studjati fiż- żewġ provi kliniċi randomised li ġejjin:
Study 1 Study 1 was a phase 3, multi-centre, three-arm, randomised, open-label study in previously untreated patients with advanced renal cell carcinoma and with 3 or more of 6 pre-selected prognostic risk factors (less than one year from time of initial RCC diagnosis to randomisation, Karnofsky performance status of 60 or 70, haemoglobin less than the lower limit of normal, corrected calcium of greater than 10 mg/ dl, lactate dehydrogenase > 1.5 times the upper limit of normal, more than one metastatic organ site).
Studju 1 Studju 1 kien studju multiċentriku ta 'fażi 3, li kien fih tliet partijiet, randomised, open- label li sar fuq pazjenti li ma kinux ikkurati fil- passat u li kellhom karċinoma avvanzata taċ- ċelluli renali (RCC), u bi 3 jew iktar minn 6 fatturi ta ’ riskju pronjostiku magħżula minn qabel (inqas minn sena miż- żmien tad - dijanjosi inizjali ta ’ RCC sar- randomisation, stat tal- prestazzjoni ta ’ Karnofsky ta ’ 60 jew 70, emoglobina inqas minn mil- limitu t’ isfel tan- normal, livell ta ’ kalċju kkoreġut ta ’ aktar minn 10 mg/ dl, lactate dehydrogenase > 1. 5 darbiet tal- limitu ta ’ fuq tan- normal, aktar minn sit wieħed ta ’ organu metastatiku).
Secondary endpoints included progression-free survival (PFS), objective response rate (ORR), clinical benefit rate, time to treatment failure (TTF), and quality adjusted survival measurement.
Ir- riżultat aħħari primarju kienet is- sopravivenza totali (overall survival - OS) Ir- riżultati aħħarin sekondarji kienu jinkludu sopravivenza mingħajr progressjoni (progression- free survival - PFS), ir- rata ta ’ rispons oġġettiv (objective response rate - ORR), ir- rata tal- benefiċċju kliniku, iż - żmien għall- falliment tal- kura (time to treatment failure - TTF), u l- kejl tas- sopravivenza aġġustat skond il- kwalità.
Patients were stratified for prior nephrectomy status within three geographic regions and were randomly assigned (1:1:1) to receive IFN-α alone (n = 207), TORISEL alone (25 mg weekly; n = 209), or the combination of IFN-α and TORISEL (n = 210).
Il- pazjenti kienu stratifikati għall- istat tan- nefrektomija fil- passat fi tliet żoni ġeografiċi u kienu assenjati b’ mod random (1: 1: 1) biex jirċievu (IFN- α) waħdu (n = 207), TORISEL waħdu (25 mg darba f’ ġimgħa; n = 209), jew il- kumbinazzjoni IFN- α u TORISEL (n = 210).
In Study 1, TORISEL 25 mg was associated with a statistically significant advantage over IFN-α in the primary endpoint of OS at the 2nd pre-specified interim analysis (n = 446 events, p = 0.0078).
Fi Studju 1, TORISEL 25 mg kien assoċjat ma ’ vantaġġ statistikament sinifikanti fuq IFN- α fir- riżultat aħħari primarju ta ’ OS fit- 2ni analiżi interim pre- speċifika (n = 446 avvenimenti, p = 0. 0078).
The TORISEL arm showed a 49% increase in median OS compared with the IFN-α arm.
Il- parti ta ’ l- istudju ta ’ TORISEL uriet żieda ta ’ 49% fil- medjan ta ’ OS meta mqabbel mal- parti ta ’ l- istudju ta ’ IFN- α.
TORISEL also was associated with statistically significant advantages over IFN-α in the secondary endpoints of PFS, TTF, and clinical benefit rate.
TORISEL kien assoċjat ukoll ma ’ vantaġġi statistikament sinifikanti fuq IFN- α fir- riżultati aħħarin sekondarji ta ’ PFS, TTF, u r- rata tal- benefiċċju kliniku.
7.3 months, hazard ratio = 0.93, p = 0.4902).
Il- kumbinazzjoni TORISEL 15 mg u IFN- α ma rriżultatx f' żieda sinifikanti fis- sopravivenza totali meta mqabbla ma 'IFN- α waħdu jew fl- analiżi interim (medjan ta' 8. 4 kontra 7. 3 xhur, proporzjon tal - periklu = 0. 96, p = 0. 6965), jew l- analiżi finali (medjan ta '8. 4 kontra 7. 3 xhur, proporzjon tal- periklu = 0. 93 p = 0. 4902).
Treatment with the combination of TORISEL and IFN-α resulted in a statistically significant increase in the incidence of certain grade 3-4 adverse events (weight loss, anaemia, neutropaenia, thrombocytopaenia and mucosal inflammation) when compared with the adverse events observed in the IFN-α or TORISEL-alone arms.
Il- kura bil- kumbinazzjoni ta ’ TORISEL u IFN- α irriżultat f’ żieda statistikament sinifikanti fl- inċidenza ta ’ ċerti avvenimenti avversi ta ’ grad 3- 4 (telf ta ’ piż, anemija, newtropenja, tromboċitopenja u infjammazzjoni mukuża) meta mqabbla ma ’ l- avvenimenti avversi osservati fil - partijiet ta ’ l- istudju ta ’ IFN- α jew ta ’ TORISEL waħidhom.
Summary of efficacy results in TORISEL Study 1 a
10 Sommarju tar- Riżultati ta 'l- Effikaċja fi Studju 1 ta' TORISEL
n = 207
IFN- α n = 207
(95% CI)
Proporzjon tal - periklu (95% CI) b
Pre-specified interim analysis Median overall survival, Months
Analiżi interim pre- speċifika
7.3 (6.1,
totali
(95% CI) Final analysis
Xhur (95% CI)
12.7)
0. 0078
0.0078
0. 73 (0. 58, 0. 92)
0.73 (0.58, 0.92)
Analiżi finali
Median overall survival, Months
Medjan tas - sopravivenza
(95% CI) Median Progression- Free
totali Xhur (95% CI) Medjan tal - Progressjoni - Sopravivenza
10.9 (8.6, 12.7)
10. 9 (8. 6, 12. 7)
8.8)
7. 3 (6. 1, 8. 8)
0.0252
0. 0252
0.78 (0.63, 0.97)
0. 78 (0. 63, 0. 97)
assessment Months (95% CI) Median Progression- Free
Ħielsa minn evalwazzjoni indipendenti Xhur (95% CI) Medjan tal - Progressjoni - Sopravivenza Ħielsa minn
5.6 (3.9, 7.2)
5. 6 (3. 9, 7. 2)
4.0)
3. 2 (2. 2, 4. 0)
0.0042
0. 0042
0.74 (0.60, 0.91)
0. 74 (0. 60, 0. 91)
assessment Months (95% CI) Overall response rate by
evalwazzjoni mill - investigatur Xhur (95% CI) Rata tar- rispons globali minn
3.8 (3.6, 5.2)
3. 8 (3. 6, 5. 2)
2.2)
1. 9 (1. 9, 2. 2)
0.0028
0. 0028
0.74 (0.60, 0.90)
0. 74 (0. 60, 0. 90)
5.3 (2.3,
0. 1361c
independent assessment% (95% CI)
evalwazzjoni indipendenti% (95% CI)
9.1 (5.2, 13.0)
9. 1 (5. 2, 13. 0)
0.1361
5. 3 (2. 3 8. 4)
CI = confidence interval; NA = not applicable. a.
CI = intervall tal- kunfidenza; NA = mhux applikabbli. a.
Based on log-rank test stratified by prior nephrectomy and region. b.
Ibbażata fuq it- test log- rank, stratifikat skond in- nefrektomija fil- passat u skond ir- reġjun. b.
Based on Cox proportional hazard model stratified by prior nephrectomy and region (95% CI are descriptive, only). c.
Ibbażat fuq il- mudell tal- periklu proporzjonali ta 'Cox, stratifikat skond in- nefrektomija fil- passat u skond ir- reġjun. ċ.
Based on Cochran-Mantel-Hansel test stratified by prior nephrectomy and region.
Ibbażat fuq it- test Cochran- Mantel- Haenszel, stratifikat skond in- nefrektomija fil- passat u skond ir - reġjun.
In Study 1, 31% of patients treated with TORISEL were 65 or older.
Fi Studju 1, 31% tal- pazjenti kkurati b’ TORISEL kellhom 65 sena jew aktar.
In patients younger than 65, median overall survival was 12 months (95% CI 9.9, 14.2) with a hazard ratio of 0.67 (95% CI 0.52, 0.87) compared with those treated with IFN-α.
F’ pazjenti li għandhom inqas minn 65 sena, il- medjan tas- sopravivenza totali kien ta ’ 12- il xahar (95% CI 9. 9, 14. 2) bi proporzjon tal- periklu ta ’ 0. 67 (95% CI 0. 52, 0. 87) meta mqabbel ma ’ dawk il- pazjenti kkurati b’ IFN - α.
In patients 65 or older, median overall survival was 8.6 months (95% CI 6.4, 11.5) with a hazard ratio of 1.15 (95% CI 0.78, 1.68) compared with those treated with IFN-α.
F’ pazjenti li għandhom iktar minn 65 sena, il- medjan tas- sopravivenza totali kien ta ’ 8. 6 xhur (95% CI 6. 4, 11. 5) bi proporzjon tal- periklu ta ’ 1. 15 (95% CI 0. 78, 1. 68) meta mqabbel ma ’ dawk il- pazjenti kkurati b’ IFN- a.
Study 2 Study 2 was a randomised, double-blind, multi-centre, outpatient trial to evaluate the efficacy, safety, and pharmacokinetics of three dose levels of TORISEL when administered to previously treated patients with advanced RCC.
11 Studju 2 Studju 2 kien prova randomised, double- blind, multiċentriku, u outpatient biex jevalwa l- effikaċja, is - sigurtà, u l- farmakokinetiċi ta ’ tliet livelli ta ’ doża ta ’ TORISEL meta jingħata lil pazjenti li kienu kkurati qabel, li kellhom RCC avvanzata.
The primary efficacy endpoint was ORR, and OS was also evaluated.
Ir- riżultat aħħar ta ’ l- effikaċja primarja kien l- ORR, u l- OS kien ukoll evalwat.
One hundred eleven (111) patients were randomly assigned in a 1:1:1 ratio to receive 25 mg, 75 mg, or 250 mg temsirolimus intravenous weekly.
Mija u ħdax- il (111) pazjent kienu assenjati b’ mod random fi proporzjon ta ’ 1: 1: 1 biex jirċievu 25 mg, 75 mg, jew 250 mg ta ’ temsirolimus ġol- vini darba f’ ġimgħa.
In the 25 mg arm (n = 36), all patients had metastatic disease; 4 (11%) had no prior chemo- or immunotherapy; 17 (47%) had one prior treatment, and 15 (42%) had 2 or more prior treatments for RCC.
Fil- parti ta ’ l - istudju fejn il- pazjenti kienu qed jingħataw 25 mg (n = 36), il- pazjenti kollha kellhom mard metastatiku; 4 (11%) qatt ma kienu ħadu kimoterapija jew immunoterapija qabel; 17 (47%) kellhom kura waħda fil- passat, u 15 (42%) kellhom 2 jew aktar kuri għal RCC.
Twenty-seven (27, 75%) had undergone a nephrectomy.
Sebgħa u għoxrin (27, 75%) kellhom nefrektomija fil- passat.
Twenty-four (24, 67%) were Eastern Cooperative Oncology Group (ECOG) performance status (PS) = 1, and 12 (33%) were ECOG PS = 0.
Erbgħa u għoxrin (24, 67%) kienu Eastern Cooperative Oncology Group (ECOG) performance status (PS) = 1, u 12 (33%) kienu ECOG PS = 0.
For patients treated weekly with 25 mg temsirolimus OS was 13.8 months (95% CI:
Għal pazjenti kkurati kull ġimgħa b’ 25 mg ta ’ temsirolimus, l- OS kien ta ’ 13. 8 xhur (95% CI:
9.0, 18.7 months); ORR was 5.6% (95% CI:
9. 0, 18. 7 xhur); l- ORR kienet 5. 6% (95% CI:
0.7, 18.7%).
0. 7, 18. 7%).