qanastek/EMEA-V3 huggingface dataset:
Prior to the first infusion, patients must receive premedication with an antihistamine and a corticosteroid.
Qabel l- ewwel infużjoni, il- pazjenti jridu jirċievu premedikazzjoni b’ antistamina u kortikosterojdi.
This premedication is recommended prior to all subsequent infusions.
Din il- premedikazzjoni hi rrakkomandata qabel l- infużjonijiet kollha li jingħataw wara.
In all indications, Erbitux is administered once a week.
Fl- indikazzjonijiet kollha, Erbitux jingħata darba f’ ġimgħa.
The very first dose is 400 mg cetuximab per m² body surface area.
L- ewwel doża hi ta ’ 400 mg ta ’ cetuximab għal kull m² ta ’ erja tas- superfiċje tal- ġisem.
All subsequent weekly doses are 250 mg/ m² each.
Id- dożi kollha li jingħataw wara ta ’ kull ġimgħa huma ta ’ 250 mg/ m² kull waħda.
2 Colorectal cancer
2 Kanċer tal- kolon u tar- rektum
In patients with metastatic colorectal cancer, cetuximab is used in combination with chemotherapy or as a single agent (see section 5.1).
F’ pazjenti b’ kanċer metastatiku tal- kolon u tar- rektum, cetuximab jintuża flimkien mal- kimoterapija jew bħala mediċina waħidha (ara sezzjoni 5. 1).
It is recommended that the detection of KRAS mutational status be performed by an experienced laboratory using a validated test method.
Hu rrakkomandat li l- għarfien ta ’ l- istat tal- mutazzjoni ġene KRAS jitwettaq f’ laboratorju b’ esperjenza fl- użu ta ’ metodu vverifikat tat- test.
For the dosage or recommended dose modifications of concomitantly used chemotherapeutic agents, refer to the product information for these medicinal products.
Għal tibdil fid- dożaġġ jew fid- doża rakkomandata ta ’ mediċini kemoterapewtiċi li jintużaw fl- istess ħin, irreferi għall- informazzjoni tal- prodott għal dawn il- prodotti mediċinali.
They must not be administered earlier than 1 hour after the end of the cetuximab infusion.
Dawn m’ għandhomx jingħataw qabel siegħa wara t- tmiem ta ’ l- infużjoni b’ cetuximab.
It is recommended that cetuximab treatment be continued until progression of the underlying disease.
Hu rrakkomandat li l- kura b’ cetuximab titkompla sakemm jitrażżan il- progress tal- marda prinċipali.
Squamous cell cancer of the head and neck
Kanċer taċ- ċelluli skwamużi fir- ras u fl- għonq
In patients with locally advanced squamous cell cancer of the head and neck, cetuximab is used concomitantly with radiation therapy.
F’ pazjenti b’ kanċer lokalment avvanzat taċ- ċelluli skwamużi fir- ras u fl- għonq, cetuximab jintuża flimkien mat- terapija bir- raġġi.
It is recommended to start cetuximab therapy one week before radiation therapy and to continue cetuximab therapy until the end of the radiation therapy period.
Hu rrakkomandat li tibda t- terapija b’ cetuximab ġimgħa qabel it- terapija bir- raġġi u li tkompli t- terapija b’ cetuximab sat- tmiem tal- perijodu tat- terapija bir- raġġi.
In patients with recurrent and/ or metastatic squamous cell cancer of the head and neck, cetuximab is used in combination with platinum-based chemotherapy followed by cetuximab as maintenance therapy until disease progression (see section 5.1).
F’ pazjenti b' kanċer taċ- ċelluli skwamużi fir- ras u fl- għonq, rikorrenti u/ jew metastatiku, cetuximab jintuża flimkien ma ’ kimoterapija bbażata fuq il- platinum segwit minn cetuximab bħala kura tal- manteniment sal- progressjoni tal- marda (ara sezzjoni 5. 1).
Chemotherapy must not be administered earlier than 1 hour after the end of the cetuximab infusion.
Il- kimoterapija m’ għandhiex tingħata qabel siegħa wara t- tmiem ta ’ l- infużjoni b’ cetuximab.
Erbitux 2 mg/ ml is administered intravenously via in-line filtration with an infusion pump, gravity drip or a syringe pump (for handling instructions, see section 6.6).
Erbitux 2 mg/ ml jingħata minn ġol- vina permezz ta ’ filtrazzjoni in- line b’ pompa ta ’ l- infużjoni, gravity drip jew pompa tas- siringa (għal struzzjonijiet dwar l- immaniġġjar ara sezzjoni 6. 6).
For the initial dose, the recommended infusion period is 120 minutes.
Għall- ewwel doża, il- perijodu rrakkomandat ta ’ l- infużjoni hu ta ’ 120 minuta.
For the subsequent weekly doses, the recommended infusion period is 60 minutes.
Għad- dożi l- oħra ta ’ kull ġimgħa, il- perijodu rrakkomandat ta ’ l- infużjoni hu ta ’ 60 minuta.
The maximum infusion rate must not exceed 10 mg/ min, equivalent to 5 ml/ min of Erbitux 2 mg/ ml.
Ir- rata massima ta ’ l- infużjoni ma tridx taqbeż 10 mg/ min, ekwivalenti għal 5 ml/ min ta ’ Erbitux 2 mg/ ml.
Special populations
Gruppi speċjali
Only patients with adequate renal and hepatic function have been investigated to date (see section 4.4).
Pazjenti li kellhom funzjoni adegwata tal- kliewi u tal- fwied biss kienu investigati s’ issa (ara sezzjoni 4. 4).
Cetuximab has not been studied in patients with pre-existing haematological disorders (see section 4.4).
Cetuximab ma kienx studjat f’ pazjenti li kellhom disturbi ematoloġiċi li kienu jeżistu minn qabel (ara sezzjoni 4. 4).
No dose adjustment is required in the elderly, but the experience is limited in patients 75 years of age and above.
L- ebda aġġustament fid- doża mhu meħtieġ f’ persuni anzjani, iżda l- esperjenza hi limitata f’ pazjenti ta ’ iktar minn 75 sena.
There is no experience in children (see section 4.4).
M’ hemmx esperjenza dwar l- użu fit- tfal (ara sezzjoni 4. 4).
Erbitux is contraindicated in patients with known severe (grade 3 or 4) hypersensitivity reactions to cetuximab.
Erbitux hu kontra- indikat f’ pazjenti li għandhom reazzjonijiet severi ta ’ sensittività eċċessiva (grad 3 jew 4) għal cetuximab li jafu bihom.
Before initiation of combination treatment, contraindications for concomitantly used chemotherapeutic agents or radiation therapy must be considered.
Qabel il- bidu tal- kura kkombinata, wieħed għandu jagħti kas tal- kontra- indikazzjonijiet għal mediċini kemoterapewtiċi li jintużaw fl- istess ħin jew għat- terapija bir- raġġi.
Infusion-related reactions
Reazzjonijiet marbuta ma ’ l- infużjoni
If the patient experiences a mild or moderate infusion-related reaction, the infusion rate may be decreased.
Jekk il- pazjent ikollu reazzjoni ħafifa jew moderata marbuta ma’ l- infużjoni, ir- rata ta ’ l- infużjoni tista ’ titnaqqas.
It is recommended to maintain this lower infusion rate in all subsequent infusions.
Hu rrakkomandat li żżomm din ir- rata tal- infużjoni aktar baxxa fl- infużjonijiet sussegwenti kollha.
Severe infusion-related reactions have been reported in patients treated with cetuximab (see section 4.8).
Reazzjonijiet severi marbuta ma ’ l- infużjoni kienu rrappurtati f’ pazjenti kkurati b’ cetuximab (ara sezzjoni 4. 8).
Symptoms usually occurred during the first infusion and up to 1 hour after the end of infusion, but may occur after several hours or with subsequent infusions.
Is- sintomi normalment seħħew matul l- ewwel infużjoni u sa siegħa wara t- tmiem ta ’ l- infużjoni, iżda jistgħu iseħħu wara diversi sigħat jew ma ’ l- infużjonijiet sussegwenti.
It is recommended to warn patients of the possibility of such a late onset and instruct them to contact their physician if symptoms of an infusion-related reaction occur.
Hu rrakkomandat li l- pazjenti jiġu mwissija dwar il- possibbiltà ta ’ reazzjonijiet bħal dawn li jseħħu wara ċertu żmien, u jingħataw parir biex jikkuntattjaw lit- tabib tagħhom jekk iseħħu sintomi marbuta ma ’ l- infużjoni.
Occurrence of a severe infusion-related reaction requires immediate and permanent discontinuation of cetuximab therapy and may necessitate emergency treatment.
Fil- kas ta ’ reazzjoni severa marbuta ma ’ l- infużjoni hemm bżonn li din titwaqqaf immedjatament u ma tingħata qatt iżjed terapija b’ cetuximab u l- pazjent jista ’ jkollu bżonn ta ’ kura urġenti.
Special attention is recommended for patients with reduced performance status and pre-existing cardio-pulmonary disease.
Attenzjoni speċjali hi rrakkomandata għal pazjenti li ma jkunux jifilħu biżżejjed jew b’ mard kardjo- pulmonari li kien jeżisti minn qabel.
Respiratory disorders
Disturbi tan- nifs
Individual cases of interstitial lung disorders of unknown causal relationship to cetuximab have been reported.
Kienu rrapurtati każi waħdiet ta ’ disturbi interstizjali tal- pulmun, li mhux magħrufa jekk għandhomx x’ jaqsmu ma ’ l- għoti ta ’ cetuximab.
If interstitial lung disease is diagnosed, cetuximab must be discontinued and the patient be treated appropriately.
Jekk jinstab mard interstizjali tal- pulmun, cetuximab għandu jitwaqqaf u l- pazjent jiġi kkurat kif ikun xieraq.
If a patient experiences a severe skin reaction (≥ grade 3; US National Cancer Institute - Common Toxicity Criteria, NCI-CTC), cetuximab therapy must be interrupted.
Jekk pazjent ikollu reazzjoni severa tal- ġilda (≥ grad 3; US National Cancer Institute - Common Toxicity Criteria, NCI- CTC), it- terapija b’ cetuximab għandha tieqaf.
Treatment may only be resumed, if the reaction has resolved to grade 2 (see section 4.8).
Il- kura tista ’ titkompla biss jekk ir- reazzjoni tkun tjiebet għal grad 2 (ara sezzjoni 4. 8).
If the severe skin reaction occurred for the first time, treatment may be resumed without any change in dose level.
Jekk ir- reazzjoni severa tal- ġilda tkun seħħet għall- ewwel darba, il- kura tista ’ titkompla mingħajr l- ebda tibdil fil- livell tad- doża.
With the second and third occurrences of severe skin reactions, cetuximab therapy must again be interrupted.
Mat- tieni u t- tielet reazzjonijiet severi tal- ġilda, it- terapija b’ cetuximab għandha terġa ’ tieqaf mill- ġdid.
Treatment may only be resumed at a lower dose level (200 mg/ m² body surface area after the second occurrence and 150 mg/ m² after the third occurrence), if the reaction has resolved to grade 2.
Il- kura tkun tista ’ titkompla biss b’ doża iktar baxxa (200 mg/ m² ta ’ l- erja tas- superfiċje tal- ġisem wara t- tieni okkorrenza, u b’ 150 mg/ m² wara t- tielet okkorrenza), jekk ir- reazzjoni tkun tjiebet għal grad 2.
If severe skin reactions occur a fourth time or do not resolve to grade 2 during interruption of treatment, permanent discontinuation of cetuximab treatment is required.
Jekk reazzjonijiet severi tal- ġilda jseħħu għar- raba ’ darba jew ma jfiequx għal grad 2 matul l- interruzzjoni tal- kura, allura hemm bżonn li l- kura b’ cetuximab tieqaf għal kollox.
Electrolyte disturbances
Disturbi fl- elektroliti
Progressively decreasing serum magnesium levels occur frequently and may lead to severe hypomagnesaemia.
Livelli ta ’ magnesium li jonqsu b’ mod progressiv jistgħu jseħħu b’ mod frekwenti u jistgħu jwasslu għal ipomanjesemija severa.
Hypomagnesaemia is reversible following discontinuation of cetuximab.
L- ipomanjesemija hi riversibbli wara t- twaqqif ta ’ cetuximab.
In addition, hypokalaemia may develop as a consequence of diarrhoea.
Flimkien ma ’ dan, l- ipokalemija tista ’ tiżviluppa bħala konsegwenza tad- dijarea.
Hypocalcaemia may also occur; in particular in combination with platinum-based chemotherapy the frequency of severe hypocalcaemia may be increased.
L- ipokalċimja tista ’ sseħħ ukoll; b’ mod partikulari flimkien ma ’ kimoterapija bbażata fuq il- platinum il- frekwenza ta ’ ipokalċimja severa tista ’ tiżdied.
Determination of serum electrolyte levels is recommended prior to and periodically during cetuximab treatment.
Id- determinazzjoni tal- livelli ta ’ l- elektroliti fis- serum hi rrakkomandata qabel, u perjodikament, matul il- kura b’ cetuximab.
Electrolyte repletion is recommended, as appropriate.
Hu rrakkomandat li jingħataw elektroliti, skond kif ikun meħtieġ.
4 Neutropenia and related infectious complications
4 In- newtropenja u kumplikazzjonijiet infettivi marbuta magħha.
Patients who receive cetuximab in combination with platinum-based chemotherapy are at an increased risk for the occurrence of severe neutropenia, which may lead to subsequent infectious complications such as febrile neutropenia, pneumonia or sepsis.
Pazjenti li jirċievu cetuximab flimkien ma ’ kimoterapija bbażata fuq il- platinum huma f’ riskju miżjud għall- okkorrenza ta ’ newtropenja severa, li tista ’ twassal għal kumplikazzjonijiet infettivi sussegwenti bħal newtropenja bid- deni, pnewmonja jew b’ xi mikrobu ieħor.
Careful monitoring is recommended in such patients, in particular in those who experience skin lesions, mucositis or diarrhoea that may facilitate the occurrence of infections (see section 4.8).
Monitoraġġ bl- attenzjoni hu rakkomandat f’ dawn il- pazjenti, b’ mod partikulari f’ dawk li jkollhom leżjonijiet fil- ġilda, mukożite jew dijarea li jistgħu jiffaċilitaw l- okkorrenza ta ’ infezzjonijiet (ara sezzjoni 4. 8).
Only patients with adequate renal and hepatic function have been investigated to date (serum creatinine ≤ 1.5fold, transaminases ≤ 5fold and bilirubin ≤ 1.5fold the upper limit of normal).
Pazjenti li kellhom funzjoni adegwata tal- kliewi u tal- fwied biss kienu investigati s’ issa (krejatinina tas- serum ≤ 1. 5 darba iktar, transaminases ≤ 5 darbiet iktar u bilirubina ≤ 1. 5 darba iktar mil- Limitu ta ’ Fuq tan- Normal (Upper Limit of Normal - ULN)).
Cetuximab has not been studied in patients presenting with one or more of the following laboratory parameters: • haemoglobin < 9 g/ dl • leukocyte count < 3000/ mm³ • absolute neutrophil count < 1500/ mm³ • platelet count < 100000/ mm³
Cetuximab ma kienx studjat f’ pazjenti li kellhom wieħed jew iktar mill- parametri tal- laboratorju li ġejjin: • emoglobina < 9 g/ dl • għadd tal- lewkoċiti < 3000/ mm³ • għadd assolut tan- newtrofili < 1500/ mm³ • għadd tal- plejtlits < 100000/ mm³
The safety and effectiveness of cetuximab in paediatric patients have not been established.
Is- sigurtà u l- effikaċja ta ’ cetuximab f’ pazjenti pedjatriċi ma ġewx stabbiliti.
There is limited experience in the use of cetuximab in combination with radiation therapy in colorectal cancer.
Hemm esperjenza limitata dwar l- użu ta ’ cetuximab flimkien ma ’ terapija bir- raġġi fil- każ ta ’ kanċer tal- kolon u tar- rektum.
In combination with platinum-based chemotherapy, the frequency of severe leukopenia or severe neutropenia may be increased, and thus may lead to a higher rate of infectious complications such as febrile neutropenia, pneumonia and sepsis compared to platinum-based chemotherapy alone (see section 4.4).
Flimkien ma ’ kimoterapija bbażata fuq il- platinum, il- frekwenza ta ’ lewkopenja severa jew ta ’ newtropenja severa tista ’ tiżdied, u għaldaqstant tista ’ twassal għal rata ogħla ta ’ kumplikazzjonijiet infettivi sussegwenti bħal newtropenja bid- deni, pnewmonja jew b’ xi mikrobu ieħor meta mqabbel ma ’ kimoterapija bbażata fuq il- platinum waħidha (ara sezzjoni 4. 4).
In combination with infusional 5-fluorouracil, the frequency of cardiac ischaemia including myocardial infarction and congestive heart failure as well as the frequency of hand-foot syndrome (palmar-plantar erythrodysaesthesia) were increased compared to that with infusional 5-fluorouracil.
Flimkien ma ’ 5- fluorouracil infużjonali, il- frekwenza ta ’ iskemija kardijaka li tinkludi infart mijokardijaku u kollass konġestiv kardijaku, kif ukoll il- frekwenza tas- sindrome ta ’ l- idejn u r- riġlejn (palmar- plantar erythrodysaesthesia) żdiedet meta mqabbla ma ’ dik b’ 5- fluorouracil infużjonali.
A formal interaction study showed that the pharmacokinetic characteristics of cetuximab remain unaltered after co-administration of a single dose of irinotecan (350 mg/ m² body surface area).
Studju formali dwar l- interazzjoni wera li l- karatteristiċi farmakokinetiċi ta ’ cetuximab jibqgħu l- istess wara l- għoti flimkien ta ’ doża waħda ta ’ irinotecan (350 mg/ m² ta ’ erja tas- superfiċje tal- ġisem).
Similarly, the pharmacokinetics of irinotecan were unchanged when cetuximab was co-administered.
Bl- istess mod, il- farmakokinetika ta ’ irinotecan ma nbidletx meta cetuximab jingħata fl- istess ħin.
No other formal interaction studies with cetuximab have been performed in humans.
Ma saru l- ebda studji formali oħrajn dwar l- interazzjoni fuq il- bnedmin.
The epidermal growth factor receptor (EGFR) is involved in foetal development.
Ir- riċettur tal- fattur tat- tkabbir epidermali (epidermal growth factor receptor - EGFR) hu involut fl- iżvilupp tal- fetu.
Limited observations in animals are indicative of a placental transfer of cetuximab, and other IgG1 antibodies have been found to cross the placental barrier.
Osservazzjonijiet limitati fl- annimali jindikaw trasferiment mill- plaċenta ta ’ cetuximab, u antikorpi IgG1 oħrajn instabu li jgħaddu għall- plaċenta.
Animal data revealed no evidence of teratogenicity.
Informazzjoni dwar l- annimali ma żvelat l- ebda evidenza ta ’ teratoġeniċità.
However, dependent on the dose, an increased incidence of abortion was observed (see section 5.3).
Madankollu, skond id- doża, kienet osservata żieda fl- inċidenza ta ’ abort (ara sezzjoni 5. 3).
Sufficient data from pregnant or lactating women are not available.
M’ hemm l- ebda informazzjoni fuq nisa tqal jew li qed ireddgħu.
It is strongly recommended that Erbitux be given during pregnancy or to any woman not employing adequate contraception only if the potential benefit justifies a potential risk to the foetus.
5 Hu rrakkomandat bil- qawwa li Erbitux jingħata biss matul it- tqala jew lil kwalunkwe mara li ma tkunx qed tuża kontraċezzjoni adegwata jekk il- benefiċċju potenzjali jiġġustifika r- riskju potenzjali lill- fetu.
5 It is recommended that women do not breast-feed during treatment with Erbitux and for 2 months after the last dose, because it is not known whether cetuximab is excreted in breast milk.
Hu rrakkomandat li n- nisa ma jreddgħux matul il- kura b’ Erbitux u għal xahrejn wara l- aħħar doża, għax mhux magħruf jekk cetuximab jgħaddix fil- ħalib tas- sider.
If patients experience treatment-related symptoms affecting their ability to concentrate and react, it is recommended that they do not drive or use machines until the effect subsides.
Jekk il- pazjenti jkollhom sintomi marbuta mal- kura li jaffettwaw il- ħila tagħhom li jikkonċentraw u jirreaġixxu, hu rrakkomandat li ma jsuqux jew jużaw il- magni sakemm l- effett ibatti.
The primary undesirable effects of cetuximab are skin reactions, which occur in more than 80% of patients, hypomagnesaemia which occurs in more than 10% of patients and infusion-related reactions, which occur with mild to moderate symptoms in more than 10% of patients and with severe symptoms in more than 1% of patients.
L- effetti primarji mhux mixtieqa ta ’ cetuximab huma reazzjonijiet tal- ġilda, li jseħħu f’ iktar minn 80% tal- pazjenti, ipomanjesemija li sseħħ f’ iktar minn 10% tal- pazjenti u reazzjonijiet marbuta ma ’ l- infużjoni, li jseħħu b’ sintomi minn ħfief sa moderati f’ iktar minn 10% tal- pazjenti u b’ sintomi severi f’ iktar minn 1% tal- pazjenti.
The following definitions apply to the frequency terminology used hereafter:
Id- definizzjonijiet li ġejjin japplikaw għat- terminoloġija tal- frekwenza li tintuża minn hawn ‘ il quddiem:
Very common (≥ 1/ 10) Common (≥ 1/ 100 to < 1/ 10) Uncommon (≥ 1/ 1,000 to < 1/ 100) Rare (≥ 1/ 10,000 to < 1/ 1,000) Very rare (< 1/ 10,000) Frequency not known (cannot be estimated from the available data)
Komuni ħafna (≥ 1/ 10) Komuni (≥ 1/ 100, < 1/ 10) Mhux komuni (≥ 1/ 1, 000, < 1/ 100) Rari (≥ 1/ 10, 000, < 1/ 1, 000) Rari ħafna (< 1/ 10, 000) Frekwenza mhux magħrufa (ma tistax tittieħed stima mid- data disponibbli)
An asterisk (*) indicates that additional information on the respective undesirable effect is provided below the table.
Asterisk (*) tindika li informazzjoni addizzjonali dwar l- effett mhux mixtieq rispettiv hi pprovduta fit- tabella t’ hawn taħt.
Headache.
Uġigħ ta ’ ras.
Conjunctivitis.
Konġuntivite.
Blepharitis, keratitis.
Blefarite, keratite.
Pulmonary embolism.
Emboliżmu pulmonari.
Diarrhoea, nausea, vomiting.
Dijarea, nawseja, rimettar.
Skin and subcutaneous tissue disorders
6 Disturbi fil- ġilda u fit- tessuti ta ’ taħt il- ġilda
Skin reactions*.
Reazzjonijiet tal- ġilda *.
Superinfection of skin lesions*.
Superinfezzjoni ta ’ leżjonijiet tal- ġilda *.
6 Metabolism and nutrition disorders
Disturbi fil- metaboliżmu
Hypomagnesaemia (see section 4.4).
Ipomanjesemija (ara sezzjni 4. 4).
Dehydration, in particular secondary to diarrhoea or mucositis; hypocalcaemia (see section 4.4); anorexia which may lead to weight decrease.
Deidrazzjoni, b’ mod partikulari li tkun sekondarja għad- dijarea jew mukożite; ipokalċimja (ara sezzjoni 4. 4); anoreksja li tista ’ twassal għal tnaqqis fil- piż.
Deep vein thrombosis.
Trombożi profonda tal- vini.
Mild or moderate infusion-related reactions*; mild to moderate mucositis which may lead to epistaxis.
Reazzjonijiet ħfief jew moderati marbuta ma ’ l- infużjonijiet *; mukożite minn ħafifa sa moderat li tista ’ twassal biex wieħed jinfaraġ.
Severe infusion-related reactions*, fatigue.
Reazzjonijiet severi marbuta ma ’ l- infużjonijiet *, għeja kbira.
Increase in liver enzyme levels (ASAT, ALAT, AP).
Żieda fil- livelli ta ’ l- enzimi tal- fwied (ASAT, ALAT, AP).
Overall, no clinically relevant difference between genders was observed.
Globalment, l- ebda differenza klinikament rilevanti bejn is- sessi ma kienet osservata.
Mild or moderate infusion-related reactions are very common comprising symptoms such as fever, chills, dizziness, or dyspnoea that occur in a close temporal relationship mainly to the first cetuximab infusion.
Reazzjonijiet ħfief jew moderati marbuta ma ’ l- infużjonijiet huma komuni ħafna, li jinkludu sintomi bħal deni, tertir ta ’ bard, sturdament, jew qtugħ ta ’ nifs li jseħħu speċjalment ftit ħin wara l- ewwel infużjoni b’ cetuximab.
Severe infusion-related reactions may commonly occur, in rare cases with fatal outcome.
Reazzjonijiet severi marbuta ma ’ l- infużjonijiet jistgħu jseħħu b’ mod komuni, u f’ każijiet rari dawn jistgħu ikunu fatali.
They usually develop during or within 1 hour of the initial cetuximab infusion, but may occur after several hours or with subsequent infusions.
Dawn normalment jiżviluppaw waqt jew fi żmien siegħa wara l- infużjoni inizjali b’ cetuximab, iżda jistgħu jseħħu wara diversi sigħat jew ma ’ infużjonijiet sussegwenti.
Although the underlying mechanism has not been identified, some of these reactions may be anaphylactoid/ anaphylactic in nature and may include symptoms such as bronchospasm, urticaria, hypotension, loss of consciousness or shock.
Għalkemm il- mekkaniżmu bażiku ma kienx identifikat, xi wħud minn dawn ir- reazzjonijiet jistgħu jkunu anafilattojdi/ anafilattiċi fin- natura tagħhom, u jistgħu jinkludu sintomi per eżempju bronkospażmu, urtikarja, pressjoni tad- demm baxxa ħafna, li tintilef minn sensik jew xokk.
In rare cases, angina pectoris, myocardial infarction or cardiac arrest have been observed.
F’ każijiet rari, anġina pectoris, infart mijokardijaku jew waqfien kardijaku kienu osservati.
For clinical management of infusion-related reactions, see section 4.4.
Għal immaniġġjar kliniku ta ’ reazzjonijiet marbuta ma ’ l- infużjonijiet, ara sezzjoni 4. 4.
Skin reactions
7 Reazzjonijiet tal- ġilda
Skin reactions may develop in more than 80% of patients and mainly present as acne-like rash and/ or, less frequently, as pruritus, dry skin, desquamation, hypertrichosis, or nail disorders (e. g. paronychia).
Reazzjonijiet tal- ġilda jistgħu jiżviluppaw f’ iktar minn 80% tal- pazjenti u primarjament jidhru bħala raxx qisu akne u/ jew, b’ mod inqas spiss, bħal ħakk, ġilda xotta, ġilda misluħa, ipertrikosi, jew mard fid- dwiefer (eż. paronikija).
Approximately 15% of the skin reactions are severe, including single cases of skin necrosis.
Madwar 15% tar- reazzjonijiet tal- ġilda huma severi, inklużi każi waħdiet ta ’ nekrosi tal- ġilda.
The majority of skin reactions develop within the first three weeks of therapy.
Il- maġġoranza tar- reazzjonijiet tal- ġilda jiżviluppaw matul l- ewwel tliet ġimgħat tat- terapija.
They generally resolve, without sequelae, over time following cessation of treatment if the recommended adjustments in dose regimen are followed (see section 4.4).
Dawn ġeneralment ifiequ maż- żmien wara li tieqaf il- kura, mingħajr ma jkun hemm l- ebda kundizzjonijiet jew mard b’ konsegwenza tagħhom, jekk l- aġġustamenti rrakkomandati fil- kors tad- doża jkunu segwiti (ara sezzjoni 4. 4).
According to NCI-CTC, grade 2 skin reactions are characterised by rash up to 50% of body surface area, while grade 3 reactions affect equal or more than 50% of body surface area.
Skond l- NCI- CTC, ir- reazzjonijiet tal- ġilda ta ’ grad 2 huma kkaratterizzati minn raxx sa 50% ta ’ l- erja tas- superfiċje tal- ġisem, filwaqt li reazzjonijiet ta ’ grad 3 jaffettwaw 50% jew iktar ta ’ l- erja tas- superfiċje tal- ġisem.
7 Skin lesions induced by cetuximab may predispose patients to superinfections (e. g. with S. aureus), which may lead to subsequent complications, e. g. cellulitis, erysipelas, or, potentially with fatal outcome, staphylococcal scalded skin syndrome or sepsis.
Leżjonijiet fil- ġilda kkaġunati minn cetuximab jistgħu jippredisponu lill- pazjenti għal superinfezzjonijiet (eż. b’ S. aureus), li jistgħu jinfexxu f’ kumplikazzjonijiet oħra, eż. ċellulite, erysipelas, jew, potenzjalment b’ riżultat fatali, is- sindrome ta ’ ġilda mismuta bi staphylococcus jew b’ xi mikrobu ieħor.
Combination treatment
Il- kura flimkien
When cetuximab is used in combination with chemotherapeutic agents, also refer to their respective product information.
Meta cetuximab jintuża flimkien ma ’ mediċini kemoterapewtiċi, irreferi wkoll għall- informazzjoni tal- prodott rispettiva tagħhom.
In combination with local radiation therapy of the head and neck area, additional undesirable effects were those typical of radiation therapy (such as mucositis, radiation dermatitis, dysphagia or leukopenia, mainly presenting as lymphocytopenia).
Flimkien mat- terapija lokali bir- raġġi taż- żona tar- ras u ta ’ l- għonq, effetti addizzjonali mhux mixtieqa kienu dawk tipiċi tat- terapija bir- raġġi (bħal mukożite, dermatite minħabba r- radjazzjoni, disfaġja jew lewkopenja, primarjament li tidher bħala limfoċitopenja).
In a randomised controlled clinical study with 424 patients, reporting rates of severe acute radiation dermatitis and mucositis as well as of late radiation-therapy-related events were slightly higher in patients receiving radiation therapy in combination with cetuximab than in those receiving radiation therapy alone.
Fi studju kliniku randomised fuq 424 pazjent, instab li r- rati ta ’ dermatite akuta u severa minħabba r- raġġi u mukożite, kif ukoll ta ’ avvenimenti li seħħew wara ċertu żmien marbuta mat- terapija bir- raġġi, kienu ftit ogħla f’ pazjenti li kienu qed jirċievu t- terapija bir- raġġi flimkien ma ’ cetuximab, milli f’ dawk li kienu qed jirċievu t- terapija bir- raġġi biss.
There is limited experience with single doses higher than 400 mg/ m² body surface area to date or weekly administrations of doses higher than 250 mg/ m² body surface area.
Hemm esperjenza limitata b’ dożi waħidhom ogħla minn 400 mg/ m² ta ’ erja tas- superfiċje tal- ġisem s’ íssa jew l- għoti kull ġimgħa ta ’ dożi ogħla minn 250 mg/ m² ta ’ erja tas- superfiċje tal- ġisem.
In clinical studies with doses up to 700 mg/ m² given every 2 weeks the safety profile was consistent with that described in section 4.8.
Fi studji kliniċi b’ dożi sa 700 mg/ m² mogħtija kull ġimagħtejn, il- profil tas- sigurtà kien konsistenti ma ’ dak deskritt f’ sezzjoni 4. 8.
Antineoplastic agents, monoclonal antibodies, ATC code:
Mediċini antineoplastiċi, antikorpi monoklonali, Kodiċi ATC:
Mechanism of action
8 Mekkaniżmu ta ’ kif jaħdem
Cetuximab is a chimeric monoclonal IgG1 antibody that is specifically directed against the epidermal growth factor receptor (EGFR).
Cetuximab hu antikorp kimeriku monoklonali IgG1 li hu speċifikament immirat kontra l- fattur tat- tkabbir epidermali (epidermal growth factor receptor - EGFR).
EGFR signalling pathways are involved in the control of cell survival, cell cycle progression, angiogenesis, cell migration and cellular invasion/ metastasis.
Il- messaġġi li jibagħtu EGFR għandhom x’ jaqsmu ma ’ kemm jgħixu ċ- ċelluli, l- iżvilupp taċ- ċiklu taċ- ċelluli, l- anġjoġenesi, kif iċ- ċelluli jgħaddu minn post għall- ieħor, u l- invażjoni/ metastasi ċellulari.
Cetuximab binds to the EGFR with an affinity that is approximately 5- to 10fold higher than that of endogenous ligands.
Cetuximab jeħel ma ’ l- EGFR b’ affinità li hi ta ’ madwar 5 sa 10 darbiet aktar minn dik ta ’ ligandi endoġeniċi.
Cetuximab blocks binding of endogenous EGFR ligands resulting in inhibition of the function of the receptor.
Cetuximab jimblokka t- twaħħil ta ’ ligandi EGFR endoġeniċi li jfixkel il- funzjoni tar- riċettur.
It further induces the internalisation of EGFR, which can lead to down-regulation of EGFR.
Flimkien ma ’ dan, jikkaġuna l- assimilazzjoni ta ’ EGFR, li tista ’ twassal biex titrażżan il- funzjoni ta ’ EGFR.
Cetuximab also targets cytotoxic immune effector cells towards EGFR-expressing tumour cells (antibody dependent cell-mediated cytotoxicity, ADCC).
Cetuximab għandu fil- mira wkoll iċ- ċelluli effector immuni ċitotossiċi lejn ċelluli tat- tumur li jesprimu EGFR (antibody dependent cell- mediated cytotoxicity, ADCC).
8 Cetuximab does not bind to other receptors belonging to the HER family.
Cetuximab ma jeħilx ma ’ riċetturi oħrajn li jappartienu għall- familja HER.
The protein product of the proto-oncogene KRAS (Kirsten rat sarcoma 2 viral oncogene homologue) is a central down-stream signal-transducer of EGFR.
Il- prodott tal- proteina tal- proto- oncogene KRAS (Kirsten rat sarcoma 2 viral oncogene homologue) hi central down- stream signal- transducer ta ’ EGFR.
In tumours, activation of KRAS by EGFR contributes to EGFR-mediated increased proliferation, survival and the production of pro-angiogenic factors.
Fit- tumuri, l- attivazzjoni tal- ġene KRAS minn EGFR tikkontribwixxi għal żieda fil- proliferazzjoni medjata minn EGFR, fis- sopravivenza u fil- produzzjoni ta ’ fatturi pro- anġjoġeniċi.
KRAS is one of the most frequently activated oncogenes in human cancers.
KRAS hi waħda mill- aktar oncogenes li jkunu attivati b’ mod frekwenti f’ kanċers tal- bniedem.
Mutations of the KRAS gene at certain hot-spots (mainly codons 12 and 13) result in constitutive activation of the KRAS protein independently of EGFR signalling.
Il- mutazzjonijiet tal- ġene KRAS f’ ċerti hot- spots (primarjament codons 12 u 13) jirriżultaw f’ attivazzjoni kostituttiva tal- proteina KRAS, indipendentement mis- senjalazzjoni ta ’ EGFR.
In both in vitro and in vivo assays, cetuximab inhibits the proliferation and induces apoptosis of human tumour cells that express EGFR.
Fl- analiżi kemm in vitro u kemm in vivo, cetuximab jinibixxi l- proliferazzjoni u jikkaġuna apoptosi ta ’ ċelluli tat- tumur tal- bniedem li jesprimu EGFR.
In vitro cetuximab inhibits the production of angiogenic factors by tumour cells and blocks endothelial cell migration.
In vitro, cetuximab jinibixxi l- produzzjoni ta ’ fatturi anġjoġeniċi minn ċelluli tat- tumur u jimblokka l- migrazzjoni taċ- ċelluli endoteljali.
In vivo cetuximab inhibits expression of angiogenic factors by tumour cells and causes a reduction in tumour neo-vascularisation and metastasis.
In vivo, cetuximab jinibixxi l- espressjoni ta ’ fatturi anġjoġeniċi minn ċelluli tat- tumur u jikkawża tnaqqis fin- neo- vaskularizzazzjoni u l- metastasi tat- tumur.
Immunogenicity
Immunoġeniċità
The development of human anti-chimeric antibodies (HACA) is a class effect of monoclonal chimeric antibodies.
L- iżvilupp ta ’ human anti- chimeric antibodies (HACA) (antikorpi anti- kimeriċi umani) hu effett ta ’ klassi ta ’ antikorpi kimeriċi monoklonali.
Current data on the development of HACAs is limited.
Informazzjoni kurrenti fuq l- iżvilupp ta ’ HACA hi limitata.
Overall, measurable HACA titres were noted in 3.4% of the patients studied, with incidences ranging from 0% to 9.6% in the target indication studies.
Globalment, livelli ta ’ HACA li jistgħu jitkejlu, kienu osservati f’ 3. 4% tal- pazjenti li kienu studjati, b’ inċidenzi li jvarjaw minn 0% sa 9. 6% fl- istudji ta ’ l- indikazzjoni fil- mira.
No conclusive data on the neutralising effect of HACAs on cetuximab is available to date.
S’ issa, m’ hemm l- ebda informazzjoni konklużiva dwar l- effett li l- HACA għandhom biex jinnewtralizzaw cetuximab.
The appearance of HACA did not correlate with the occurrence of hypersensitivity reactions or any other undesirable effect to cetuximab.
Id- dehra ta ’ HACA ma kkorrelatx ma ’ l- okkorrenza ta ’ reazzjonijiet ta ’ sensittività eċċessiva jew ma kwalunkwe effetti oħrajn mhux mixtieqa ta ’ cetuximab.
Colorectal cancer
Kanċer tal- kolon u tar- rektum
A diagnostic assay (EGFR pharmDx) was used for immunohistochemical detection of EGFR expression in tumour material.
Assaġġ dijanjostiku (EGFR pharmDx) intuża għall- iskoperta immunoistokimika ta ’ l- espressjoni EGFR f’ materjal tat- tumur.
A tumour was considered to be EGFR-expressing, if one stained cell could be identified.
It- tumur kien ikkunsidrat li jkun jesprimi EGFR jekk ċellula waħda li tkun immarkata tkun tista ’ tiġi identifikata.
Approximately 75% of the patients with metastatic colorectal cancer screened for clinical studies had an EGFR-expressing tumour and were therefore considered eligible for cetuximab treatment.
Madwar 75% tal- pazjenti b’ kanċer metastatiku tal- kolon u tar- rektum li kienu magħzula għall- istudji kliniċi, kellhom tumur li kien jesprimi EGFR u għalhekk kienu kkunsidrati eliġibbli għall- kura b’ cetuximab.
The efficacy and safety of cetuximab have not been documented in patients with tumours where EGFR was not detected.
L- effikaċja u s- sigurtà ta ’ cetuximab ma kienux dokumentati f’ pazjenti b’ tumuri fejn l- EGFR ma kienx osservat.
In metastatic colorectal cancer, the incidence of KRAS mutations is in the range of 30 - 50%.
9 F’ kanċer metastatiku tal- kolon u tar- rektum, l- inċidenza ta ’ mutazzjonijiet tal- ġene KRAS hi fil- medda ta ’ 30 - 50%.
Recent data demonstrate that patients with KRAS wild-type metastatic colorectal cancer have a significantly higher chance to benefit from treatment with cetuximab or a combination of cetuximab and chemotherapy.
Dejta riċenti turi li pazjenti b’ kanċer metastatiku tal- kolon u tar- rektum b’ ġene wild- type KRAS għandhom ċans ogħla b’ mod sinifikanti li jibbenefikaw mill- kura b’ cetuximab jew minn kumbinazzjoni ta ’ cetuximab u kimoterapija.
Cetuximab as a single agent or in combination with chemotherapy was investigated in 5 randomised controlled clinical studies and several supportive studies.
Cetuximab bħala mediċina waħidha jew flimkien mal- kimoterapija kien investigat f’ 5 studji kliniċi kkontrollati u randomised, u diversi studji ta ’ appoġġ.
The 5 randomised studies investigated a total of 3734 patients with metastatic colorectal cancer, in whom EGFR expression was detectable and who had an ECOG performance status of ≤ 2.
Il- 5 studji randomised investigaw total ta ’ 3734 pazjent b’ kanċer metastatiku tal- kolon u tar- rektum, li fihom, l- espressjoni EGFR kienet osservata u li kellhom stat ta ’ prestazzjoni ECOG ta ’ ≤ 2.
The majority of patients included had an ECOG performance status of ≤ 1.
Il- maġġoranza ta ’ pazjenti inklużi kellhom stat ta ’ prestazzjoni ECOG ta ’ ≤ 1.
In all studies, cetuximab was administered as described in section 4.2.
Fl- istudji kollha, cetuximab ingħata kif deskritt f’ sezzjoni 4. 2.
The KRAS status was recognised as predictive factor for the treatment with cetuximab in 4 of the randomised controlled studies.
L- istat ta ’ ġene KRAS kien rikonoxxut bħala fattur li jbassar għall- kura b’ cetuximab f’ 4 mill- istudji randomised ikkontrollati.
KRAS mutational status was available for 1261 patients.
L- istat tal- mutazzjoni KRAS kien disponibbli għal 1261 pazjent.
Only in study EMR 62 202-007, an analysis was not possible.
Kien biss fi studju EMR 62 202- 007 li analiżi ma kinitx possibbli.
9 Cetuximab in combination with chemotherapy
Cetuximab flimkien mal- kimoterapija
This randomised study in patients with metastatic colorectal cancer who had not received prior treatment for metastatic disease compared the combination of cetuximab and irinotecan plus infusional 5-fluorouracil/ folinic acid (5-FU/ FA) (599 patients) to the same chemotherapy alone (599 patients).
Dan l- istudju randomised studji f’ pazjenti b’ kanċer metastatiku tal- kolon u tar- rektum li ma kinux irċivew kura fil- passat għal marda metastatika qabbel il- kumbinazzjoni ta ’ cetuximab u irinotecan flimkien ma ’ 5- fluorouracil/ folinic acid (5- FU/ FA) infużjonali (599 pazjent) ma ’ l- istess kimoterapija waħidha (599 pazjenti).
The proportion of patients with KRAS wild-type tumours from the patient population evaluable for KRAS status comprised 64%.
Il- proporzjon ta ’ pazjenti b’ tumuri wild- type ġene KRAS mill- popolazzjoni ta ’ pazjenti li setgħu jkunu evalwati għall- istat tal- ġene KRAS kien ta ’ 64%.
The efficacy data generated in this study are summarised in the table below:
L- informazzjoni dwar l- effikaċja li ħarġet minn dan l- istudju hi deskritta fil- qosor fit- tabella hawn taħt:
Overall population
Popolazzjoni totali
KRAS wild-type population
Ġene KRAS popolazzjoni wild- type
Variable/ statistic
Varjabbli/ statistika
Cetuximab
Cetuximab flimkien ma ’ FOLFIRI
Cetuximab FOLFIRI Cetuximab
FOLFIRI Cetuximab flimkien ma ’ FOLFIRI
(N=172)
(N=599) (N=172)
% (95% CI) p-value PFS
% (95% CI) valur p
46.9
46. 9
(42.9, 51.0) 38.7 0.0038
(42. 9, 51. 0) 38. 7 0. 0038
(34.8, 42.8)
(34. 8, 42. 8)
59.3
59. 3
(51.6, 66.7) 43.2 0.0025
(51. 6, 66. 7) 43. 2 0. 0025
(35.8, 50.9)
(35. 8, 50. 9)
Hazard Ratio (95% CI) p-value
Proporzjon ta ’ riskju
0.85 (0.726, 0.998) 0.0479
0. 68 (0. 501, 0. 934)
0.68 (0.501, 0.934) 0.0167
valur p
CI = confidence interval, FOLFIRI = irinotecan plus infusional 5-FU/ FA, ORR = objective response rate (patients with complete response or partial response), PFS = progression-free survival time
CI = intervall tal- kunfidenza, FOLFIRI = irinotecan flimkien ma ’ 5- FU/ FA infużjonali, ORR = rata ta ’ rispons oġġettiv (pazjenti b’ rispons sħiħ jew b’ rispons parzjali), PFS = żmien ta ’ sopravivenza mingħajr progressjoni
This randomised study in patients with metastatic colorectal cancer who had not received prior treatment for metastatic disease compared the combination of cetuximab and oxaliplatin plus infusional 5-fluorouracil/ folinic acid (5-FU/ FA) (169 patients) to the same chemotherapy alone (168 patients).
Dan l- istudju randomised f’ pazjenti b’ kanċer metastatiku tal- kolon u tar- rektum li ma kinux irċivew kura fil- passat għal mard metastatiku, qabbel il- kumbinazzjoni ta ’ cetuximab u oxaliplatin flimkien ma ’ 5- fluorouracil/ folinic acid (5- FU/ FA) infużjonali (169 pazjent) ma ’ l- istess kimoterapija waħidha (168 pazjenti).
The proportion of patients with KRAS wild-type tumours from the patient population evaluable for KRAS status comprised 58%.
Il- proporzjon ta ’ pazjenti b’ tumuri wild- type ġene KRAS mill- popolazzjoni ta ’ pazjenti li setgħu jkunu evalwati għall- istat KRAS kien ta ’ 58%.
The efficacy data generated in this study are summarised in the table below:
10 L- informazzjoni dwar l- effikaċja li ħarġet minn dan l- istudju hi deskritta fil- qosor fit- tabella hawn taħt:
Cetuximab
Cetuximab flimkien ma ’ FOLFOX
Cetuximab FOLFOX Cetuximab
FOLFOX Cetuximab flimkien ma ’ FOLFOX
45.6
45. 6
(37.9, 53.4) 35.7 0.064
(37. 9, 53. 4) 35. 7 0. 064
(28.5, 43.5)
(28. 5, 43. 5)
60.7
60. 7
(47.3, 72.9) 37.0 0.011
(47. 3, 72. 9) 37. 0 0. 011
(26.0, 49.1)
(26. 0, 49. 1)
0.93
(95% CI)
(0.70, 1.23) 0.6170
valur p
0.57
0. 6170
(0.35, 0.91) 0.0163
0. 0163
CI = confidence interval, FOLFOX = oxaliplatin plus infusional 5-FU/ FA, ORR = objective response rate (patients with complete response or partial response), PFS = progression-free survival time
CI = intervall tal- kunfidenza, FOLFOX = oxaliplatin flimkien ma ’ 5- FU/ FA infużjonali, ORR = rata ta ’ rispons oġġettiv (pazjenti b’ rispons sħiħ jew b’ rispons parzjali), PFS = żmien ta ’ sopravivenza mingħajr progressjoni
This randomised study in patients with metastatic colorectal cancer who had received initial combination treatment with oxaliplatin plus fluoropyrimidine for metastatic disease compared the combination of cetuximab and irinotecan (648 patients) with irinotecan alone (650 patients).
Dan l- istudju randomised f’ pazjenti b’ kanċer metastatiku tal- kolon u tar- rektum li kienu rċivew kumbinazzjoni inizjali ta ’ kura b’ oxaliplatin flimkien ma ’ fluoropyrimidine għal mard metastatiku qabbel il- kumbinazzjoni ta ’ cetuximab u irinotecan (648 pazjenti) b’ irinotecan waħdu (650 pazjent).
The proportion of patients with KRAS wild-type tumours from the patient population evaluable for KRAS status comprised 64%.
Il- proporzjon ta ’ pazjenti b’ tumuri wild- type ġene KRAS mill- popolazzjoni ta ’ pazjenti li setgħu jkunu evalwati għall- istat KRAS kien ta ’ 64%.
10 A significant difference in overall survival time could not be shown in this study.
Differenza sinifikanti fiż- żmien totali ta ’ sopravivenza ma setgħetx tintwera f’ dan l- istudju.
Following disease progression, treatment with EGFR-targeting agents was initiated in 50% of patients in the irinotecan-alone arm, which most likely impacted survival results.
Wara l- progressjoni tal- marda, inbdiet il- kura b’ sustanzi li għandhom lil EGFR fil- mira, f’ 50% tal- pazjenti fil- parti ta ’ l- istudju dwar irinotecan mogħti waħdu, li x’ aktarx li kellha impatt fuq ir- riżultati tas- sopravivenza.
Objective response rate and progression free survival time were significantly improved with cetuximab.
Ir- rata ta 'rispons oġġettiv u ż- żmien ta ’ sopravivenza mingħajr progressjoni tjiebu b’ mod sinifikanti b’ cetuximab.
However, as no independent review of imaging data was conducted, these results have to be interpreted with caution.
Madankollu, minħabba li ma saret l- ebda evalwazzjoni indipendenti tad- dejta ta ’ l- immaġni, dawn ir- riżultati għandhom ikunu interpretati b’ kawtela.
This randomised study in patients with metastatic colorectal cancer after failure of irinotecan-based treatment for metastatic disease as the last treatment before study entry compared the combination of cetuximab and irinotecan (218 patients) with cetuximab monotherapy (111 patients).
Dan l- istudju randomised f’ pazjenti b’ kanċer metastatiku tal- kolon u tar- rektum wara li l- kura għall- mard metastatiku bbażata fuq irinotecan ma tkunx irnexxiet, bħala l- aħħar kura qabel ma pazjent ikun irreġistrat fl- istudju, qabbel il- kumbinazzjoni ta ’ cetuximab u irinotecan (218- il pazjent) mal- monoterapija b’ cetuximab (111- il pazjent).
The combination of cetuximab with irinotecan compared to cetuximab alone reduced the overall risk of disease progression by 46% and significantly increased objective response rate.
Il- kumbinazzjoni ta ’ cetuximab ma ’ irinotecan meta mqabbla ma ’ cetuximab waħdu, naqqset ir- riskju totali tal- progressjoni tal- marda b’ 46% u żiedet b’ mod sinifikanti r- rata ta 'rispons oġġettiv.
In the randomised trial, the improvement in overall survival time did not reach statistical significance; however, in the follow-up treatment, nearly 50% of the patients of the cetuximab alone arm received a combination of cetuximab and irinotecan after progression of disease, which may have influenced overall survival time.
Fil- prova randomised, it- titjib fiż- żmien totali ta ’ sopravivenza ma laħaqx sinifikat statistiku; madankollu, fil- kura follow- up, kważi 50% tal- pazjenti fil- parti ta ’ l- istudju b’ cetuximab waħdu, irċivew kumbinazzjoni ta ’ cetuximab u irinotecan wara l- progressjoni ta ’ marda, li setgħet influwenzat iż- żmien totali ta ’ sopravivenza.
Cetuximab as a single agent
Cetuximab bħala mediċina waħidha
This randomised study in patients with metastatic colorectal cancer who had received prior oxaliplatin-, irinotecan- and fluoropyrimidine-based treatment for metastatic disease compared the addition of cetuximab as a single agent to best supportive care (BSC) (287 patients) with best supportive care (285 patients).
Dan l- istudju randomised f’ pazjenti b’ kanċer metastatiku tal- kolon u tar- rektum li kienu rċivew kura fil- passat ibbażata fuq oxaliplatin, irinotecan u fluoropyrimidine għal mard metastatiku, qabbel iż- żieda ta ’ cetuximab bħala mediċina waħidha sa l- aħjar kura ta ’ appoġġ (BSC) (287 pazjent) bl- aħjar kura ta ’ appoġġ (285 pazjent).
The proportion of patients with KRAS wild-type tumours from the patient population evaluable for KRAS status comprised 59%.
Il- proporzjon ta ’ pazjenti b’ tumuri wild- type ġene KRAS mill- popolazzjoni ta ’ pazjenti li setgħu jkunu evalwati għall- istat KRAS kien ta ’ 59%.
Addition of cetuximab to best supportive care reduced the overall risk of death in the overall study population by 23% and the overall risk of disease progression by 32%.
11 Iż- żieda ta ’ cetuximab ma ’ l- aħjar kura ta ’ appoġġ naqqset ir- riskju totali ta ’ mewt fil- popolazzjoni totali ta ’ l- istudju bi 23% u riskju totali tal- progressjoni tal- marda bi 32%.
Preliminary data from patients with KRAS wild-type tumours showed a more pronounced beneficial effect of cetuximab on overall survival time and progression free survival time.
Dejta preliminari minn pazjenti b’ tumuri wild- type KRAS urew effett utli ta ’ cetuximab aktar notevoli fuq iż- żmien totali ta ’ sopravivenza u ż- żmien ta ’ sopravivenza mingħajr progressjoni.
Immunohistochemical detection of EGFR expression was not performed since more than 90% of patients with squamous cell cancer of the head and neck have tumours that express EGFR.
L- iskoperta immunoistokimika ta ’ l- espressjoni EGFR ma ntużatx għax iktar minn 90% tal- pazjenti b’ kanċer taċ- ċelluli skwamużi fir- ras u fl- għonq kellhom tumuri li jesprimu EGFR.
Cetuximab in combination with radiation therapy for locally advanced disease
Cetuximab flimkien ma ’ terapija bir- raġġi għal mard li jkun infirex lokalment
This randomised study compared the combination of cetuximab and radiation therapy (211 patients) with radiation therapy alone (213 patients) in patients with locally advanced squamous cell cancer of the head and neck.
Dan l- istudju randomised qabbel il- kumbinazzjoni ta ’ cetuximab u t- terapija bir- raġġi (211- il pazjent) ma ’ terapija bir- raġġi biss (213- il pazjent) f’ pazjenti b’ kanċer taċ- ċelluli skwamużi fir- ras u fl- għonq li jkun infirex lokalment.
Cetuximab was started one week before radiation therapy and administered at the doses described in section 4.2 until the end of the radiation therapy period.
Cetuximab inbeda ġimgħa qabel it- terapija bir- raġġi u ngħata b’ dożi deskritti f’ sezzjoni 4. 2 sat- tmiem tal- perijodu tat- terapija bir- raġġi.
11 The efficacy data generated in this study are summarised in the table below:
L- informazzjoni dwar l- effikaċja li ħarġet minn dan l- istudju hi deskritta fil- qosor fit- tabella hawn taħt:
Radiation therapy + cetuximab (N=211)
flimkien ma ’ cetuximab
Radiation therapy alone (N=213)
Kontroll lokoreġjonali
Locoregional control
(N=213)
months, median (95% CI)
xhur, medjan (95% CI)
24.4
24. 4
(15.7, 45.1)
(15. 7, 45. 1)
(11.8, 19.9)
(11. 8, 19. 9)
0.68 (0.52, 0.89) 0.005
valur p
49.0
49. 0
(32.8, 62.6+)
(32. 8, 62. 6+)
29.3
29. 3
(20.6, 42.8)
(20. 6, 42. 8)
0.74 (0.56, 0.97) 0.032
valur p
CI = confidence interval, OS = overall survival time, a '+ 'denotes that the upper bound limit had not been reached at cut-off
CI = intervall tal- kunfidenza, OS = żmien totali ta ’ sopravivenza, is- sinjal ‘ + ’ juri li l- upper bound limit ma ntlaħaqx fil- cut- off.
Patients with a good prognosis as indicated by tumour stage, Karnofsky performance status (KPS) and age had a more pronounced benefit, when cetuximab was added to radiation therapy.
Pazjenti bi pronjosi tajba kif indikat minn fażi tat- tumur, l- istat tal- prestazzjoni ta ’ Karnofsky (KPS) u l- età, kellhom benefiċċju iktar ċar meta cetuximab żdied mat- terapija bir- raġġi.
No clinical benefit could be demonstrated in patients with KPS ≤ 80 who were 65 years of age or older.
L- ebda benefiċċju kliniku ma deher f’ pazjenti b’ KPS ta ’ ≤ 80 li kellhom 65 sena jew iktar.
The use of cetuximab in combination with chemo-radiotherapy has so far not been adequately investigated.
L- użu ta ’ cetuximab flimkien mal- kemo- radjuterapija s’ issa ma kinitx investigata b’ mod adegwat.
Thus, a benefit-risk ratio for this combination has not yet been established.
Għaldaqstant, il- bilanċ tal- benefiċċju/ riskju għadu mhux magħruf.
Cetuximab in combination with platinum-based chemotherapy in recurrent and/ or metastatic disease
Cetuximab flimkien ma ’ kimoterapija bbażata fuq il- platinum f’ mard rikorrenti u/ jew metastatiku