qanastek/EMEA-V3 huggingface dataset:
Pregnancy There are no adequate data on the use of imatinib in pregnant women.
It- tqala M ’ hemmx tagħrif biżżejjed dwar l- użu ta ’ imatinib waqt it- tqala.
Studies in animals have however shown reproductive toxicity (see section 5.3) and the potential risk for the foetus is unknown.
Madanakollu, studji fuq bhejjem urew ħsara fuq is- sistema riproduttiva (ara sezzjoni 5. 3) u mhux magħruf ir- riskju potenzjali fuq il - fetu.
Glivec should not be used during pregnancy unless clearly necessary.
Glivec m’ għandux jintuża waqt it- tqala sakemm ma jkunx hemm bżonn ċar.
If it is used during pregnancy, the patient must be informed of the potential risk to the foetus.
Jekk jintuża waqt it - tqala, il- pazjenta għandha tkun infurmata dwar ir- riskju li jista ’ jkun hemm għall- fetu.
Women of childbearing potential must be advised to use effective contraception during treatment.
Nisa li jista ’ jkollhom it- tfal għandhom jingħataw parir biex jużaw xi mod effettiv ta ’ kontraċezzjoni waqt il- kura.
Lactation It is not known whether imatinib is excreted in human milk.
Treddiegħ Mhux magħruf jekk imatinib joħroġx fil- ħalib tas- sider tal- bniedem.
In animals, imatinib and/ or its metabolites were extensively excreted in milk.
Fl- annimali, imatinib u / jew is - sustanzi ffurmati bil- metaboliżmu tiegħu ħarġu b’ mod estensiv fil- ħalib.
Women who are taking Glivec should therefore not breast-feed.
Għaldaqstant, nisa li jkunu qed jieħdu Glivec, m’ għandhomx ireddgħu.
However, patients should be advised that they may experience undesirable effects such as dizziness or blurred vision during treatment with imatinib.
Għalkemm ma kienx hemm rapporti speċifiċi, il- pazjenti għandhom jiġu avżati li jista ’ jkollhom effetti oħra mhux mixtieqa, bħal
Therefore, caution should be recommended when driving a car or operating machinery.
Għaldaqstant, għandu jkun rakkomandat li dejjem tintuża l- kawtela waqt is- sewqan jew waqt xi tħaddim ta ’ magni.
Patients with advanced stages of malignancies may have numerous confounding medical conditions that make causality of adverse reactions difficult to assess due to the variety of symptoms related to the underlying disease, its progression, and the co-administration of numerous medicinal products.
Pazjenti li jkollhom stadji avvanzati ta ’ kanċer malinn jista ’ jkollhom għadd ta ’ kundizzjonijiet mediċi li jagħmlu l- identifikazzjoni tal- kawża ta ’ l- effetti avversi diffiċli biex tkun stmata minħabba l- varjetà ta ’ sintomi relatati mal- marda, l- avvanz tagħha, u l- għotja fl- istess ħin ta ’ numru kbir ta ’ prodotti mediċinali.
In clinical trials in CML, drug discontinuation for drug-related adverse reactions was observed in 2.4% of newly diagnosed patients, 4% of patients in late chronic phase after failure of interferon therapy, 4% of patients in accelerated phase after failure of interferon therapy and 5% of blast crisis patients after failure of interferon therapy.
Fi provi kliniċi b’ CML, it- twaqqif tal- mediċina minħabba reazzjonijiet avversi tal- mediċina kienu osservati f’ 2. 4% tal- pazjenti li jkunu għadhom kif ġew dijanjostikati, 4% tal- pazjenti fil- fażi kronika avvanzata wara li falliet terapija b’ interferon, 4% tal- pazjenti fil- fażi aċċelerata wara li falliet terapija b’ interferon u 5% tal- pazjenti bi blast crisis wara li falliet it- terapija b’ interferon.
In GIST the study drug was discontinued for drug-related adverse reactions in 4% of patients.
F’ GIST, l- istudju kellu jitwaqqaf minħabba reazzjonijiet avversi tal- mediċina f’ 4% tal- pazjenti.
The adverse reactions were similar in all indications, with two exceptions.
L- effetti avversi kienu simili fl- indikazzjonijiet kollha, bl- eċċezzjoni ta ’ tnejn.
There was more myelosuppression seen in CML patients than in GIST, which is probably due to the underlying disease.
Kien hemm aktar majelosuppressjoni f’ pazjenti b’ CML milli f’ GIST, probabbli minħabba l- marda nnifisha.
In the GIST clinical trial, 7 (5%) patients experienced CTC grade 3/ 4 GI bleeds (3 patients), intra-tumoural bleeds (3 patients) or both (1 patient).
Fil- prova klinika GIST, 7 (5%) tal- pazjenti ħassew CTC grad 3/ 4 fsada GI (3 pazjenti), fsada fit- tumur (3 pazjenti) jew it- tnejn (pazjent 1).
GI tumour sites may have been the source of the GI bleeds (see section 4.4).
Il- post fejn kienu it- tumuri GI jista ’ jkun il- kawża tal- fsada (ara sezzjoni 4. 4).
GI and tumoural bleeding may be serious and sometimes fatal.
GI u fsada tat- tumur jistgħu jkunu serji u kulltant jwasslu għall- mewt.
The most commonly reported (≥ 10%) drug-related adverse reactions in both settings were mild nausea, vomiting, diarrhoea, abdominal pain, fatigue, myalgia, muscle cramps and rash.
Fiż- żewġ każijiet, l- aktar effett avvers relatat mal- mediċina li kien rappurtat (≥ 10%) kienu tqallih ħafif, rimettar, dijarrea, uġigħ addominali, għejja, majalġja, bugħawwieġ u raxx.
Superficial oedemas were a common finding in all studies and were described primarily as periorbital or lower limb oedemas.
Edimi suprfiċjali kienu sejbiet komuni fl- istudji kollha u kienu deskritti l- aktar mad- dawra ta ’ l- għajnejn jew fir- riġlejn.
However, these oedemas were rarely severe and may be managed with diuretics, other supportive measures, or by reducing the dose of Glivec.
Madankollu, dawn l- edemi rarament kienu severi u jistgħu jkunu maniġġjati b’ dijuretiċi, miżuri ta ’ support oħrajn jew billi titnaqqas id- doża ta ’ Glivec.
9 When imatinib was combined with high dose chemotherapy in Ph+ ALL patients, transient liver toxicity in the form of transaminase elevation and hyperbilirubinaemia were observed.
Meta imitanib kien kombinat ma ’ dożi għolja ta ’ kimoterapija f’ pazjenti b’ Ph+ ALL, tossiċità mumentanja tal- fwied dehret bħala żieda fil- livelli ta ’ transaminases u bilirubin fid- demm.
Miscellaneous adverse reactions such as pleural effusion, ascites, pulmonary oedema and rapid weight gain with or without superficial oedema may be collectively described as “ fluid retention”.
Reazzjonijiet avversi varji bħall effużjoni fil- plewra, axxite, edima pulmonari u żieda mgħaġġla tal- piż b’ edima superfiċjali jew mingħajra tista ’ tkun deskritta b’ mod kollettiv bħala “ retenzjoni ta ’ fluwidi ”.
These reactions can usually be managed by withholding Glivec temporarily and with diuretics and other appropriate supportive care measures.
Dawn ir- reazzjonijiet normalment jistgħu jiġu maniġġjati billi jitwaqqaf Glivec b’ mod temporanju u b’ dijuretiċi u miżuri ta ’ kura xierqa oħrajn.
However, some of these reactions may be serious or life- threatening and several patients with blast crisis died with a complex clinical history of pleural effusion, congestive heart failure and renal failure.
Madankollu, dawn ir- reazzjonijiet jistgħu jkunu serji jew ta ’ theddida għall- ħajja u ħafna pazjenti bi blast crisis mietu wara li sofrew minn għadd kumpless ta ’ kondizzjonijiet bħall effużjoni fil- plewra, insuffiċjenza tal- qalb konġestiva, u insuffiċjenza tal- kliewi.
There were no special safety findings in paediatric clinical trials.
Ma kienx hemm sejbiet ta ’ sigurtà speċjali fi provi kliniċi pedjatriċi.
Adverse reactions Adverse reactions reported as more than an isolated case are listed below, by system organ class and by frequency.
Effetti avversi Effetti avversi li ġew irrapportati aktar minn darba huma elenkati fil- tabella li ġejja, skond is- sistema jew l- organi li jaffettwaw u skond il- frekwenza tagħhom.
Frequencies are defined as: very common (> 1/ 10), common (> 1/ 100, ≤ 1/ 10), uncommon (> 1/ 1,000, ≤ 1/ 100), rare (≤ 1/ 1,000), not known (cannot be estimated from the available data).
Il- frekwenzi huma definiti kif ġej: komuni ħafna (> 1/ 10), komuni (> 1/ 100, ≤1/ 10), mhux komuni (> 1/ 1, 000, ≤1/ 100), rari (≤1/ 1, 000), mhux magħruf (ma tistax tittieħed stima mid- data disponibbli).
Within each frequency grouping, undesirable effects are presented in order of frequency, the most frequent first.
F’ kull sezzjoni ta ’ frekwenza, l- effetti mhux mixtieqa għandhom jitniżżlu skond is- serjetà tagħhom.
Adverse reactions and their frequencies reported in Table 1 are based on the main registration studies.
Reazzjonijiet avversi u l- frekwenzi tagħhom irrappurtati f’ Tabella 1 huma bbażati fuq l- istudji ta ’ reġistrazzjoni ewlenin.
Adverse reactions in clinical studies
Reazzjonijiet avversi fl- istudji kliniċi
Weight increased Weight decreased Blood creatinine increased, blood creatine phosphokinase increased, blood lactate dehydrogenase increased, blood alkaline phosphatase increased
Żieda fil- piż Jonqos il- piż Krejatinina fid- demm tiżdied, phosphokinase fid- demm jiżdied, lactate
Blood amylase increased
dehydrogenase jiżdied, alkaline phosphatase jiżdied Rari:
Palpitations, tachycardia, cardiac failure congestive1, pulmonary oedema Arrhythmia, atrial fibrillation, cardiac arrest, myocardial infarction, angina pectoris, pericardial effusion
Arritmija, fibrillazzjoni atrijali, attakk tal- qalb, infart mijokardijaku, angina pectoris, effużjoni fil- perikardju Disturbi tad- demm u tas- sistema limfatika Komuni ħafna:
Haemolytic anaemia
Newtropenja, tromboċitopenja, anemija Panċitopenja, newtropenija bid- deni Tromboċitemija, limfopenja, dipressjoni tal- mudullun, eżinofolja, limfadenopatija Anemija emolitika
Nervous system disorders Very common:
Disturbi fis- sistema nervuża Uġigħ ta ’ ras2 Komuni ħafna:
Headache2 Dizziness, paraesthesia, taste disturbance, hypoaesthesia Migraine, somnolence, syncope, peripheral neuropathy, memory impairment, sciatica, restless leg syndrome, tremor, cerebral haemorrhage
Sturdament, paresteżija, tibdil tat- togħma, ipoesteżija Emigranja, ngħas, sinkope, newropatija periferali, tixkil fil- memorja, xjatika, sindrome tas- sieq irrekwieta, tregħid, emorraġija ċerebrali
Increased intracranial pressure, convulsions, optic neuritis
Żieda fil- pressjoni ta ’ ġol kranju, konvulżjonijiet, nevrite ottika
Eyelid oedema, lacrimation increased, conjunctival haemorrhage, conjunctivitis, dry eye, blurred vision
Edema ta ’ ħabbet il- għajn, żieda fid- dmugħ, emorraġija tal- konġuntiva, konġuntivite, għajnejn xotti, vista mċajpra
Eye irritation, eye pain, orbital oedema, scleral haemorrhage, retinal haemorrhage, blepharitis, macular oedema
Irritazzjoni ta ’ l- għajnejn, uġigħ fl- għajnejn, edema orbitali, emorraġija fl- isklera, emorraġija fir- retina, blefarite, edema makulari
Cataract, glaucoma, papilloedema
Katarretti, glawkoma, papilledema
Ear and labyrinth disorders Uncommon:
Disturbi fil- widnejn u fis- sistema labirintika Mhux komuni:
Vertigo, tinnitus, hearing loss
Vertigo, tisfir fil- widnejn, telf tas- smigħ
Respiratory, thoracic and mediastinal disorders
Disturbi respiratorji, toraċiċi u medjastinali Komuni:
Dyspnoea, epistaxis, cough Pleural effusion3, pharyngolaryngeal pain, pharyngitis Pleuritic pain, pulmonary fibrosis, pulmonary hypertension, pulmonary haemorrhage
Uġigħ fil- plewra, fibrożi fil- pulmun, pressjoni għolja fil- pulmun, emorraġija fil - pulmun
Gastrointestinal disorders Very common:
Disturbi gastro- intestinali Dardir, dijarea, rimettar, dispepsja, uġigħ fl- addome4 Komuni ħafna:
Stomatitis, mouth ulceration, gastrointestinal haemorrhage5, eructation, melaena, oesophagitis, ascites, gastric ulcer, haematemesis, cheilitis, dysphagia, pancreatitis
Gass fl- istonku, nefħa fl- addome, ittella ’ mill- istonku, stitikezza, ħalq xott, gastrite Stomatite, ulċeri fil- ħalq, emorraġija gastro- intestinali5, tifwieq, melena, esofaġite, axxite, ulċera fl- istonku, rimettar tad- demm, kejlite, disfaġja, pankrejatite
Colitis, ileus, inflammatory bowel disease
Kolite, iljus, marda ta ’ l- infjammazzjoni ta ’ l- imsaren
Renal pain, haematuria, renal failure acute, urinary frequency increased
Uġigħ renali, demm fl- awrina, insuffiċjenza renali akuta, żieda fil- frekwenza ta ’ l - awrina
Skin and subcutaneous tissue disorders Very common:
Disturbi fil- ġilda u fit- tessuti ta ’ taħt il- ġilda Komuni ħafna:
Periorbital oedema, dermatitis/ eczema/ rash Pruritus, face oedema, dry skin, erythema, alopecia, night sweats, photosensitivity reaction
Edema mad- dawra ta ’ l- għajnejn, dermatite/ ekżema/ raxx Ħakk, edema fil- wiċċ, ġilda xotta, ħmura, alopeċja, tgħereq ħafna matul il- lejl, reazzjoni ta ’ fotosensittività
Rash pustular, contusion, sweating increased, urticaria, ecchymosis, increased tendency to bruise, hypotrichosis, skin hypopigmentation, dermatitis exfoliative, onychoclasis, folliculitis, petechiae, psoriasis, purpura, skin hyperpigmentation, bullous eruptions
Raxx bil- ponot, kontużjoni, żieda fl- għaraq, urtikarja, ekkimożi, tidbenġel malajr, ipotrikożi, ipopigmentazzjoni tal- ġilda, dermatite esfoljattiva, onikoklażi, follikulite, tikkek ħomor fil- ġilda, psorajiżi, purpura, iperpigmentazzjoni tal- ġilda, joħorġu l - imsiemer
Rare:
Mhux magħruf:
Acute febrile neutrophilic dermatosis (Sweet’ s syndrome), nail discolouration, angioneurotic oedema, rash vesicular, erythema multiforme, leucocytoclastic vasculitis, Stevens-Johnson syndrome
Keratożi lichenoid, lichen planus Nekroliżi tossika tal- ġilda
Musculoskeletal and connective tissue disorders Very common:
Disturbi muskolu- skeletrali u tal- connective tissue Komuni ħafna:
Muscle spasm and cramps, musculoskeletal pain including myalgia, arthralgia, bone pain6
Spażmi fil- muskoli u bugħawwieġ, uġigħ muskoluskeletrali inklużi mijalġja, artralġja, u uġigħ fl- għadam6
Metabolism and nutrition Common:
Dgħjufija muskolari, artrite Disturbi fil- metaboliżmu u n- nutrizzjoni Komuni:
Joint swelling Joint and muscle stiffness Muscular weakness, arthritis disorders Anorexia Hypokalaemia, increased appetite, hypophosphataemia, decreased appetite, dehydration, gout, hyperuricaemia, hypercalcaemia, hyperglycaemia, hyponatraemia
Anoressija Ipokalimja, żieda fl- aptit, ipofosfatimja, nuqqas ta ’ aptit, deidratazzjoni, gotta, iperuriċemija, iperkalċimja, ipergliċemija iponatrimja
Hyperkalaemia, hypomagnesaemia
Iperkalimja, ipomagneżimja
Herpes zoster, herpes simplex, nasopharyngitis, pneumonia7, sinusitis, cellulitis, upper respiratory tract infection, influenza, urinary tract infection, gastroenteritis, sepsis
Infezzjonijiet u infestazzjonijiet Herpes zoster, herpes simplex, nasofarinġite, pnewmonja7, sinużite, ċellulite, Mhux komuni: infezzjoni tan- naħa ta ’ fuq tal- passaġġ respiratorju, influwenza, infezzjoni tal - passaġġ ta ’ l- awrina, gastro- enterite, sepsi Rari:
Fungal infection
Infezzjonijiet tal- fungu Disturbi vaskulari 8 Komuni:
Flushing, haemorrhage Hypertension, haematoma, peripheral coldness, hypotension, Raynaud’ s phenomenon
Fwawar, emorraġija Pressjoni għolja, ematoma, kesħa periferali, pressjoni baxxa, fenomenu ta ’ Raynaud
General disorders and administration site conditions Very common:
Disturbi ġenerali u kondizzjonijiet ta 'mnejn jingħata Komuni ħafna:
Fluid retention and oedema, fatigue Weakness, pyrexia, anasarca, chills, rigors Chest pain, malaise
Ritenzjoni ta ’ fluwidi u edema, għeja Dgħjufija, deni, anasarca, dehxiet, tregħid Uġigħ fis- sider, tħossok ma tiflaħx
Common:
Disturbi fil- fwied u fil- marrara Komuni:
Increased hepatic enzymes Hyperbilirubinaemia, hepatitis, jaundice Hepatic failure9, hepatic necrosis
Żieda fl- enzimi epatiċi Iperbilirubinimja, epatite, suffejra Insuffiċjenza epatika9, nekrożi epatika
Reproductive system and breast disorders
Disturbi fis- sistema riproduttiva u fis- sider Mhux komuni:
Psychiatric disorders
Ginekomastja, funzjoni ħażina ta ’ l- erezzjoni, menorraġja, mestrwazzjoni irregolari, funzjoni sesswali ħażina, uġigħ fin- nipil, tkabbir tas- sider, edema fl- iskrotu
Gynaecomastia, erectile dysfunction, menorrhagia, menstruation irregular, sexual dysfunction, nipple pain, breast enlargement, scrotal oedema
Disturbi psikjatriċi
Insomnia Depression, libido decreased, anxiety Confusional state
Nuqqas ta ’ rqad Dipressjoni, tnaqqis tal- libido, ansjetà Stat konfużjonali
1 On a patient-year basis, cardiac events including congestive heart failure were more commonly observed in patients with transformed CML than in patients with chronic CML.
1 Fuq bażi ta ’ sena- pazjent, każijiet kardijaċi inkluża insuffiċjenza tal- qalb konġestiva dehru b’ mod aktar komuni f’ pazjenti b’ CML trasformat milli f’ pazjenti b’ CML kroniku.
2 Headache was the most common in GIST patients.
2 Uġigħ ta ’ ras kien l- aktar komuni f’ pazjenti b’ GIST.
3 Pleural effusion was reported more commonly in patients with GIST and in patients with transformed CML (CML-AP and CML-BC) than in patients with chronic CML.
3 Effużjoni fil- plewra kienet irrappurtata b’ mod aktar komuni f’ pazjenti b’ GIST u f’ pazjenti b’ CML trasformat (CML- AP u CML- BC) milli f’ pazjenti b’ CML kroniku.
4+5 Abdominal pain and gastrointestinal haemorrhage were most commonly observed in GIST patients.
4+5 Uġigħ fl- addome u emorraġija gastro- intestinali dehru b’ mod l- aktar komuni f’ pazjenti b’ GIST.
6 Musculoskeletal pain and related events were more commonly observed in patients with CML than in GIST patients.
6 Uġigħ muskoluskeletrali u każijiet relatati dehru b’ mod aktar komuni f’ pazjenti b’ CML trasformat u f’ pazjenti b’ GIST.
7 Pneumonia was reported most commonly in patients with transformed CML and in patients with GIST.
7 Pnewmonja kienet irrappurtata b’ mod l- aktar komuni f’ pazjenti b’ CML trasformat u f’ pazjenti b’ GIST.
8 Flushing was most common in GIST patients and bleeding (haematoma, haemorrhage) was most common in patients with GIST and with transformed CML (CML-AP and CML-BC).
8 Fwawar kienu l- aktar komuni f’ pazjenti b’ GIST u fsada (ematoma, emorraġija) kienet l- aktar komuni f’ pazjenti b’ GIST u b’ CML trasformat (CML- AP u CML- BC).
9 Some fatal cases of hepatic failure and of hepatic necrosis have been reported.
9 Xi każijiet fatali ta ’ insuffiċjenza epatika u ta ’ nekrożi epatika kienu rrappurtati.
The following types of reactions have been reported mainly from post-marketing experience with Glivec.
Ir- reazzjonijiet li ġejjin kienu rrappurtati l- aktar mill- esperjenza ta ’ wara t- tqegħid fis- suq bi Glivec.
This includes spontaneous case reports as well as serious adverse events from ongoing studies, the expanded access programmes, clinical pharmacology studies and exploratory studies in unapproved indications.
Dan jinkludi rapporti spontanji ta ’ każijiet kif ukoll każijiet avversi serji minn studji li jkunu għaddejjin, il- programmi għal aċċess estiż, studji ta ’ farmakoloġija klinika u studji li jesploraw l- użu għal indikazzjonijiet li għadhom ma ġewx approvati.
Because these reactions are reported from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to imatinib exposure.
Peress li dawn ir- reazzjonijiet huma rrappurtati minn popolazzjoni ta ’ ċertu daqs, mhux dejjem ikun possibli li tiġi stmata b’ mod affidabbli l - frekwenza tagħhom jew li tiġi stabbilita ir- relazzjoni bejn dak li jkun qed jikkawżhom u l- esponiment għal imatinib.
Table 2
12 Tabella 2
Adverse reactions from post-marketing reports
Reazzjonijiet avversi minn rapporti ta ’ wara t- tqegħid fis- suq
Immune system disorders
Neoplażmi beninni, malinni u dawk mhux speċifikati (inklużi ċesti u polipi) Mhux magħruf:
Tumour haemorrhage/ tumour necrosis
Emorraġija tat- tumur / nekrożi tat- tumur
Not known:
Disturbi tas- sistema immuni Mhux magħruf:
Anaphylactic shock
Xokk anafilattiku
Pericarditis, cardiac tamponade
Perikardite, tamponaġġ kardijaku
Nervous system disorders Not known:
Disturbi fis- sistema nervuża Mhux magħruf:
Cerebral oedema
Edema ċerebrali
Vitreous haemorrhage
Emorraġija fil- vitriju
Respiratory, thoracic and mediastinal disorders Not known:
Disturbi respiratorji, toraċiċi u medjastinali Insuffiċjenza respiratorja akuta1, mard fl- interstizzju tal- pulmun Mhux magħruf:
Gastrointestinal disorders Not known:
Disturbi gastro- intestinali Mhux magħruf:
Ileus/ intestinal obstruction, gastrointestinal perforation, diverticulitis
Imblukkar ta ’ l- iljus/ msaren, titqib gastro- intestinali, divertikulite
Skin and subcutaneous tissue disorders Not known:
Disturbi fil- ġilda u fit- tessuti ta ’ taħt il- ġilda Mhux magħruf:
Musculoskeletal and connective tissue disorders Not known:
Disturbi muskolu- skeltrali Mhux magħruf:
Avascular necrosis/ hip necrosis
Keratożi lichenoid, lichen planus Nekroliżi tossika ta ’ l- epidermide u tal- connective tissue Nekrożi mhux vaskulari, nekrożi tal- ġenbejn
Thrombosis/ embolism
Trombożi/ emboliżmu
1 Fatal cases have been reported in patients with advanced disease, severe infections, severe neutropenia and other serious concomitant conditions.
1 Każijiet fatali kienu rrappurtati f’ pazjenti b’ mard avvanzat, infezzjonijiet severi, newtropenja severa u kundizzjonijiet serji oħrajn li kien hemm fl- istess waqt.
12 Laboratory test abnormalities Haematology In CML, cytopenias, particularly neutropenia and thrombocytopenia, have been a consistent finding in all studies, with the suggestion of a higher frequency at high doses ≥ 750 mg (phase I study).
Anormalitajiet fit- testijiet tal- laboratorju Ematoloġija Fil- każ ta ’ CML, ċitopenji, l- aktar newtropinja u tromboċitopinja, dejjem kienu sejbiet konsistenti, f’ kull studju li sar, u kien hemm anke indikazzjonijiet li l- frekwenza tagħhom kienet tiżdied meta kienu jintużaw dożi kbar ta ’ ≥ 750 mg (fl- istudju ta ’ fażi I).
However, the occurrence of cytopenias was also clearly dependent on the stage of the disease, the frequency of grade 3 or 4 neutropenias (ANC < 1.0 x 109/ l) and thrombocytopenias (platelet count < 50 x 109/ l) being between 4 and 6 times higher in blast crisis and accelerated phase (59– 64% and 44– 63% for neutropenia and thrombocytopenia, respectively) as compared to newly diagnosed patients in chronic phase CML (16.7% neutropenia and 8.9% thrombocytopenia).
Madankollu, il- frekwenzi ta ’ ċitopenji dehru biċ- ċar li kienu jiddependu wkoll fuq l- istadju tal- marda, tant li l- frekwenzi ta ’ newtropinji tat - 3 jew ir- 4 grad (ANC < 1. 0 x 109/ l) u tromboċitpenji (għadd tal- plejtlets < 50 x 109/ l) kienu bejn 4- 6 darbiet ogħla fil- blast crisis jew fil- fażi l- imgħaġġla (59- 64% u 44- 63% fil- każijiet ta ’ newtropinja u tromboċitopenja, rispettivament) meta mqabbla mal- frekwenzi li wieħed kien isib fil- każijiet ta ’ pazjenti li tkun għada kif ġiet dijanjostikata CML fil- fażi l- kronika (16. 7% newtropinja u 8. 9% tromboċitopenja).
In newly diagnosed chronic phase CML grade 4 neutropenia (ANC < 0.5 x 109/ l) and thrombocytopenia (platelet count < 10 x 109/ l) were observed in 3.6% and < 1% of patients, respectively.
F’ CML, fil- fażi l- kronika, li kienet għada kif ġiet dijanjostikata, kien hemm newtropinja tar- 4 grad (ANC < 0. 5 x 109/ l) u tromboċitopenja (għadd tal- plejtlets < 10 x 109/ l) f ’ 3. 6% u f ’ < 1% tal- pazjenti, rispettivament.
The median duration of the neutropenic and thrombocytopenic episodes usually ranged from 2 to 3 weeks, and from 3 to 4 weeks, respectively.
Dawn il- fażijiet ta ’ newtropinja u tromboċitopenja damu medja ta ’ bejn 2- 3 ġimgħat u minn 3 sa 4 ġimgħat, rispettivament.
These events can usually be managed with either a reduction of the dose or an interruption of treatment with Glivec, but can in rare cases lead to permanent discontinuation of treatment.
Dawn l- effetti s- soltu jitilqu jew bi tnaqqis fid- doża, jew inkella billi l- kura b’ Glivec tieqaf għal ftit, biss f’ xi każijiet rari għandu mnejn ikun hemm bżonn li l- kura saħansitra titwaqqaf għal kollox.
In paediatric CML patients the most frequent toxicities observed were grade 3 or 4 cytopenias involving neutropenia, thrombocytopenia and anaemia.
F’ pazjenti pedjatriċi b’ CML, l- aktar tossiċitajiet frekwenti kienu ċitopenji ta ’ grad 3 jew 4 li jinvolvu newtropenji, tromboċitopenji u anemija.
These generally occur within the first several months of therapy.
Dawn normalment iseħħu fl- ewwel għadd ta ’ xhur tat- terapija.
In patients with GIST, grade 3 and 4 anaemia was reported in 5.4% and 0.7% of patients, respectively, and may have been related to gastrointestinal or intra-tumoural bleeding in at least some of these patients.
F ’ pazjenti b’ GIST, seħħet anemija tat- 3 u r- 4 grad fi 5. 4% u f ’ 0. 7% tal- pazjenti, rispettivament, u jista ’ jagħti l- każ li din l- anemija kienet riżultat ta ’ emorraġiji fis- sistema gastro- intestinali jew fit - tumur, għallinqas f’ xi wħud minn dawn il- pazjenti.
Grade 3 and 4 neutropenia was seen in 7.5% and 2.7% of patients, respectively, and grade 3 thrombocytopenia in 0.7% of patients.
Newtropinja ta ’ grad 3 u grad 4 kienet evidenti f ’ 7. 5% f ’ 2. 7% tal- pazjenti, rispettivament, u tromboċitopenja ta ’ grad 3 f ’ 0. 7% tal- pazjenti.
No patient developed grade 4 thrombocytopenia.
L- ebda pazjent ma żviluppa tromboċitopenja tar- 4 grad.
The decreases in white blood cell (WBC) and neutrophil counts occurred mainly during the first six weeks of therapy, with values remaining relatively stable thereafter.
It- tnaqqis fl- għadd ta ’ ċelluli bojod (WBC) u fl- għadd ta ’ newtrofili kien iseħħ l- aktar tul l- ewwel sitt ġimgħat tat- terapija, u minn hemm- il quddiem il- livelli kienu jibqgħu relattivament stabbli.
Biochemistry Severe elevation of transaminases (< 5%) or bilirubin (< 1%) was seen in CML patients and was usually managed with dose reduction or interruption (the median duration of these episodes was approximately one week).
13 Biokimika Żieda qawwija fil- livelli tat- transaminases (< 5%) jew tal- bilirubin (< 1%) kienet evidenti f’ pazjenti b’ CML u s- soltu kienet kontrollata bi tnaqqis fid- doża jew inkella billi kien imwaqqaf għal ftit żmien it– trattament (it- tul medjan ta ’ dawn l- episodji kien ta ’ bejn wieħed u ieħor, ġimgħa).
In GIST patients (study B2222), 6.8% of grade 3 or 4 ALT (alanine aminotransferase) elevations and 4.8% of grade 3 or 4 AST (aspartate aminotransferase) elevations were observed.
Il- kura kellha titwaqqaf għall- kollox, minħabba abnormalitajiet fit- testijiet tal- laboratorju fuq il- funzjoni tal- fwied, f’ inqas minn 1% tal- pazjenti b’ CML. F’ pazjenti b’ GIST (studju B2222), żiediet ta ’ 6. 8% tal- grad 3 jew 4 ALT (alanine aminotransferase) u żiediet ta ’ 4. 8% ta ’ grad 3 jew 4 AST (aspartate aminotransferase) kienu evidenti.
Bilirubin elevation was below 3%.
Iż- żieda fil- bilirubin kienet taħt 3%.
There have been cases of cytolytic and cholestatic hepatitis and hepatic failure; in some of them outcome was fatal, including one patient on high dose paracetamol.
Kien hemm xi każijiet ta ’ epatite ċitolitika u kolestatika u anke każijiet ta ’ insuffiċjenza epatika; uħud minn dawn kienu fatali, inkluż il- każ ta ’ pazjent li kien fuq dożi għoljin ta ’ paracetamol.
Experience with doses greater than 800 mg is limited.
L- esperjenza b’ dożi ta ’ aktar minn 800 mg hija limitata.
Isolated cases of Glivec overdose have been reported.
Każijiet iżolati ta ’ doża eċċessiva ta ’ G; ivec kienu rappurtati.
A patient with myeloid blast crisis inadvertently took Glivec 1,200 mg for 6 days and experienced Grade 1 elevations of serum creatinine, Grade 2 ascites and elevated liver transaminase levels, and Grade 3 elevations of bilirubin.
Pazjent li kellu majelojd blast crisis, bi żball ħa Glivec 1, 200 mg għal 6 ijiem u b’ riżultat ta ’ dan kellu żiediet ta ’ Grad 1 fil- livelli tal- kreatinina, axxite ta ’ Grad 2 u żiediet fil- livelli ta ’ transaminases tal - fwied, u żiediet ta ’ Grad 3 fil- livelli tal- bilirubin.
Treatment was temporarily interrupted and there was complete reversal of all abnormalities within one week.
It- terapija twaqqfet għal ftit żmien u l- anormalitajiet kollha reġgħu lura għan- normal fi żmien ġimgħa.
Treatment was resumed at a dose of 400 mg without recurrence of problems.
Imbagħad reġa beda il- kura b’ doża ta ’ 400 mg mingħajr ma reġa kien hemm problemi.
Another patient developed severe muscle cramps after taking Glivec 1,600 mg daily for six days.
Pazjent ieħor żviluppa bugħawwieġ qawwi wara li ħa 1, 600 mg Glivec kuljum għal sitt ijiem.
Following interruption of treatment, complete resolution of muscle cramps occurred, treatment was subsequently resumed.
Wara li waqqaf il- kura, il- bugħawwieġ għaddewlu għall - kollox, u l- kura reġgħet imbdiet.
In the event of overdose, the patient should be observed and appropriate supportive treatment given.
F’ każ ta ’ doża eċċessiva, l- pazjent għandu jibqa taħt osservazzjoni u kura xierqa ta ’ support għandha tingħata.
Pharmacotherapeutic group: protein-tyrosine kinase inhibitor, ATC code:
Kategorija farmakoterapewtika: sustanza li tinpedixxi l- enzima protein- tyrosine kinase, Kodiċi ATC:
Imatinib is a protein-tyrosine kinase inhibitor which potently inhibits the Bcr-Abl tyrosine kinase at the in vitro, cellular and in vivo levels.
Imatinib huwa sustanza li tinpedixxi l- enzima protein- tyrosine kinase li b’ saħħa tinpedixxi lill- Bcr- Abl tyrosine kinase fil- livelli in vitro, ċellulari u in vivo.
The compound selectively inhibits proliferation and induces apoptosis in Bcr-Abl positive cell lines as well as fresh leukaemic cells from Philadelphia chromosome positive CML and acute lymphoblastic leukaemia (ALL) patients.
Din is- sutanza tinpedixxi b’ mod selettiv il - proliferazzjoni u tistimola apoptożi f’ linji ta ’ ċelluli li jkunu pożittivi għal Bcr- Abl kif ukoll f’ ċelluli lewkimiċi friski li jinstabu f’ pazjenti li jkollhom CML li tkun pożittiva għall- kromosoma ta ’ Filadelfja u f’ pazjenti b’ acute lymphoblastic leukaemia (ALL).
In vivo the compound shows anti-tumour activity as a single agent in animal models using Bcr-Abl positive tumour cells.
In vivo, is- sustanza hija attiva kontra t- tumuri, anke meta tintuża ’ waħidha f’ annimali mudelli b’ ċelluli tat- tumuri li jkunu pożittivi għal Bcr- Abl.
Imatinib is also an inhibitor of the receptor tyrosine kinases for platelet-derived growth factor (PDGF), PDGF-R, and stem cell factor (SCF), c-Kit, and inhibits PDGF- and SCF-mediated cellular events.
Imatinib jinpedixxi wkoll lir- receptor tyrosine kinases għall- growth factor derivat mill- plejtlets (PDGF), PDGF- R, u l- istem cell factor( SCF), c- Kit, u b’ hekk jinpedixxi effetti fil- livell ċellulari li jkunu assoċjati ma ’ PDGF u ma ’ SCF.
In vitro, imatinib inhibits proliferation and induces apoptosis in gastrointestinal stromal tumour (GIST) cells, which express an activating kit mutation.
In vitro, imatinib jinibixxi l- proliferazzjoni u jistimola l - apoptożi fiċ- ċelluli tat- tumur stromali gastro- intestinali (GIST), liema ċelluli jkunu jesprimu mutazzjoni kit li tattiva.
Constitutive activation of the PDGF receptor or the Abl protein tyrosine kinases as a consequence of fusion to diverse partner proteins or constitutive production of PDGF have been implicated in the pathogenesis of MDS/ MPD, HES/ CEL and DFSP.
Attivazzjoni kostituttiva tar- riċettur PDGF jew Abl protein tyrosine kinases bħala konsegwenza tal- fużjoni ma ’ proteini diversi imseħħbin jew produzzjoni kostituttiva ta ’ PDGF kienu implikati fil- patoġenesi ta ’ MDS/ MPD, HES/ CEL u DFSP.
Imatinib inhibits signalling and proliferation of cells driven by dysregulated PDGFR and Abl kinase activity.
Imatinib jinibixxi s- sinjalar u l - proliferazzjoni ta ’ ċelluli mmexxija minn PDGFR regolat ħażin u attività ta ’ Abl kinase.
Clinical studies in chronic myeloid leukaemia The effectiveness of Glivec is based on overall haematological and cytogenetic response rates and progression-free survival.
Studji kliniċi fil- majelojd lewkimja kronika L- effikaċja ta ’ Glivec hija bbażata fuq ir- rati ta ’ rispons globali ematoloġiċi u ċitoġenetiċi u sopravivenza mingħajr avvanz.
Except in newly diagnosed chronic phase CML, there are no controlled trials demonstrating a clinical benefit, such as improvement in disease-related symptoms or increased survival.
14 dijanjostikata, ma hemmx provi b’ kontroll li juru xi benefiċċju mill- aspett kliniku, bħal xi titjib fis - sintomi li għandhom x’ jaqsmu mal- marda jew xi żieda fis- sopravivenza.
Three large, international, open-label, non-controlled phase II studies were conducted in patients with Philadelphia chromosome positive (Ph+) CML in advanced, blast or accelerated phase disease, other Ph+ leukaemias or with CML in the chronic phase but failing prior interferon-alpha (IFN) therapy.
Saru tliet studji kbar fuq livell internazzjonali, tat- tip open- label u mingħajr il- kontroll fil- fażi II, fuq pazjenti li kellhom CML li kienet pożittiva għall- kromosoma ta’ Filadelfja (Ph+), fil- fażi avvanzata, blast, jew aċċelerata, u fuq pazjenti b’ tipi oħrajn ta ’ lewkimja li huma Ph+, jew pazjenti b’ CML fil - fażi kronika imma li fil- każ tagħhom l- kura bl- interferon- alpha (IFN) minn qabel ma ħadmitx.
One large, open-label, multicentre, international randomised phase III study has been conducted in patients with newly diagnosed Ph+ CML.
Sar studju wieħed kbir tat- tip open- label, f’ ħafna ċentri, internazzjonali u randomised fil- fażi III f’ pazjenti li tkun għada kemm saritilhom id- dijanjosi ta ’ CML li tkun Ph+.
In addition, children have been treated in two phase I studies and one phase II study.
Minbarra hekk, tfal kienu kurati f’ żewġ studji ta ’ fażi I u wieħed ta ’ Fażi II.
In all clinical studies 38– 40% of patients were ≥ 60 years of age and 10– 12% of patients were ≥ 70 years of age.
Fl- istudji kliniċi kollha 38- 40% tal- pazjenti kellhom ≥ 60 sena u 10- 12% tal- pazjenti kellhom ≥ 70 sena.
Chronic phase, newly diagnosed:
Il- fażi l- kronika, li tkun għada kif ġiet dijanjostikata:
This phase III study in adult patients compared treatment with either single-agent Glivec or a combination of interferon-alpha (IFN) plus cytarabine (Ara-C).
Dan l- istudju ta’ fażi III qabbel il- kura b’ Glivec waħdu mal- kura b’ taħlita ta ’ interferon- alpha (IFN) u cytarabine (Ara- C) flimkien.
Patients showing lack of response (lack of complete haematological response (CHR) at 6 months, increasing WBC, no major cytogenetic response (MCyR) at 24 months), loss of response (loss of CHR or MCyR) or severe intolerance to treatment were allowed to cross over to the alternative treatment arm.
Dawk il- pazjenti li wrew nuqqas ta ’ rispons għall- kura (nuqqas ta ’ rispons ematoloġiku sħiħ (CHR) mas- 6 xahar, numru ta ’ ċelluli bojod li jkun qed jiżdied, l- ebda rispons ċitoġenetiku sinifikanti (MCyR) sar- 24 xahar), jew li ma baqgħux jirrispondu għall- kura daqs kemm kienu fil- bidu (telfien ta ’ CHR jew ta ’ MCyR), jew li wrew intolleranza qawwija għall- kura, tħallew jaqilbu minn tip ta ’ trattament għall- ieħor.
In the Glivec arm, patients were treated with 400 mg daily.
F’ dawk li ħadu Glivec, id- doża kienet ta ’ 400 mg kuljum.
In the IFN arm, patients were treated with a target dose of IFN of 5 MIU/ m2/ day subcutaneously in combination with subcutaneous Ara-C 20 mg/ m2/ day for 10 days/ month.
F ’ dawk li ħadu IFN, il- pazjenti kienu kurati b’ doża mira ta ’ IFN ta ’ 5 MIU/ m2/ jum, taht il- ġilda, flimkien ma ’ Ara- C 20 mg/ m2/ jum, taħt il- ġilda, għal 10 ijiem/ xahar.
A total of 1,106 patients were randomised, 553 to each arm.
Total ta ’ 1, 106 pazjenti tqassmu b’ mod randomized, 553 f’ kull fergħa ta ’ trattament.
Baseline characteristics were well balanced between the two arms.
Il- karatteristiċi tal- linja bażika kienu bilanċjati sew bejn iż- żewġ fergħat.
Median age was 51 years (range 18– 70 years), with 21.9% of patients ≥ 60 years of age.
L- età medjana kienet ta ’ 51 sena (minn 18- 70 sena), b ’ 21. 9% tal- pazjenti jkollhom ≥ 60 sena.
There were 59% males and 41% females; 89.9% caucasian and 4.7% black patients.
59% kienu rġiel filwaqt li 41% kienu nisa; 89. 9% kienu kawkasi u 4. 7% kienu pazjenti suwed.
Five years after the last patient had been recruited, the median duration of first-line treatment was 60 and 8 months in the Glivec and IFN arms, respectively.
Ħames snin wara li kien reklutat l- aħħar pazjent, iż- żmien medjan ta ’ kemm damet il- kura preferita kien 60 u 8 xhur fil- friegħi bi Glivec u IFN, rispettivament.
The median duration of second-line treatment with Glivec was 45 months.
Iż- żmien medjan ta ’ kemm damet il- kura tat- tieni għażla bi Glivec kien 45 xahar.
Overall, in patients receiving first-line Glivec, the average daily dose delivered was 389 ± 71 mg.
B’ mod ġenerali, f’ pazjenti li qed jirċievu Glivec bħala l- kura preferita, il- medja tad- doża li ngħatat kuljum kienet 389 ± 71 mg.
The primary efficacy endpoint of the study is progression-free survival.
L- endpoint ta ’ l- effikaċja primarja ta ’ l- istudju hija s- sopravivenza mingħajr avvanz.
Progression was defined as any of the following events: progression to accelerated phase or blast crisis, death, loss of CHR or MCyR, or in patients not achieving a CHR an increasing WBC despite
L- avvanz kien meqjus bħala kwalunkwe minn dawn l- eventi li ġejjin: avvanz għall - fażi aċċelerata jew blast crisis, mewt, telf ta ’ CHR jew MCyR, jew f’ pazjenti li mhux qed jirċievu CHR żieda fil- WBC minkejja maniġġjar terapewtiku xieraq.
Major cytogenetic response, haematological response, molecular response (evaluation of minimal residual disease), time to accelerated phase or blast crisis and survival are main secondary endpoints.
Dejta tar- rispons qed jintwerew f’ Tabella 3.
Response data are shown in Table 3.
Tabella 3
Response in newly diagnosed CML Study (60-month data)
Studju CML li jkun għadu kif ġie dijanjostikat (tagħrif ta ’ 60- xahar)
IFN+Ara-C
Glivec IFN+Ara- C n=553 N=553
(Best response rates) Haematological response
(Ir- rati ta ’ l- aħjar rispons) Rispons ematoloġiku n (%) tar- rata ta’ CHR
CHR rate n (%)
534 (96. 6%) *
313 (56.6%)*
313 (56. 6%) *
[94.7%, 97.9%]
[94. 7%, 97. 9%]
[52.4%, 60.8%]
[52. 4%, 60. 8%]
Cytogenetic response Major response n (%)
Rispons ċitoġenetiku n (%) Rispons maġġuri
490 (88.6%)*
490 (88. 6%) *
129 (23.3%)*
129 (23. 3%) *
[95% CI] Complete CyR n (%) Partial CyR n (%)
[95% CI] n (%) ta ’ CyR sħaħ n (%) ta ’ CyR parzjali
[85.7%, 91.1%] 454 (82.1%)* 36 (6.5%)
[85. 7%, 91. 1%] 454 (82. 1%) * 36 (6. 5%)
[19.9%, 27.1%] 64 (11.6%)* 65 (11.8%)
[19. 9%, 27. 1%] 64 (11. 6%) * 65 (11. 8%)
Molecular response Major response at 12 months (%) Major response at 24 months (%) * p < 0.001, Fischer’ s exact test
Rispons molekulari Rispons Maġġuri fit- 12- il xahar (%) Rispons Maġġuri fir- 24 xahar (%)
** insufficient data, only two patients available with samples Haematological response criteria (all responses to be confirmed after ≥ 4 weeks):
** Dejta mhux suffiċjenti, żewġ pazjenti biss kienu disponibbli bil- kampjuni Kriterji ta ’ rispons ematoloġiku (ir- risponsijiet kollha jridu jkunu konfermati wara ≥ 4 ġimgħat):
WBC < 10 x 109/ l, platelet < 450 x 109/ l, myelocyte+metamyelocyte < 5% in blood, no blasts and promyelocytes in blood, basophils < 20%, no extramedullary involvement Cytogenetic response criteria: complete (0% Ph+ metaphases), partial (1– 35%), minor (36– 65%) or minimal (66– 95%).
Kriterji ta ’ rispons ċitoġenetiku: sħaħ (0% ta ’ metafasijiet Ph+), parzjali (1- 35%), minuri (36- 65%) jew minimi (66- 95%).
A major response (0– 35%) combines both complete and partial responses.
Reazzjoni ta ’ importanza (0- 35%) tiġbor flimkien kemm risponsijiet sħaħ kif ukoll dawk parzjali.
Major molecular response criteria: in the peripheral blood reduction of ≥ 3 logarithms in the amount of Bcr-Abl transcripts (measured by real-time quantitative reverse transcriptase PCR assay) over a standardised baseline.
Kriterji ta ’ rispons molekulari maġġuri: fid- demm periferali tnaqqis ta ’ ≥ 3 logaritmi fl- ammont tat- traskritti Bcr- Abl (imkejjla b’ assay ta ’ reverse transcriptase kwantitattiv li jinqara f’ dak il- ħin stess) fuq linja bażika standardizzata.
Rates of complete haematological response, major cytogenetic response and complete cytogenetic response on first-line treatment were estimated using the Kaplan-Meier approach, for which non- responses were censored at the date of last examination.
Ir- rati ta ’ rispons ematoloġiku komplet, rispons ċitoġenetiku maġġuri u rispons ċitoġenetiku komplet wara kura bit- terapija preferita kienu stmati bl- approċċ Kaplan- Meier, li bihom nuqqas ta ’ risponsijiet kienu ċensurati fil- jum ta ’ l- aħħar eżami.
Using this approach, the estimated cumulative response rates for first-line treatment with Glivec improved from 12 months of therapy to 60 months of therapy as follows:
B’ dan l- approċċ, ir- rati kumulativi stmati għall- kura preferita bi Glivec tjiebu minn 12- il xahar ta ’ terapija għal 60 xahar ta ’ terapija kif ġej:
CHR from 96.4% to 98.4% and CCyR from 69.5% to 86.7%, respectively.
CHR minn 96. 4% għal 98. 4% u CCyR minn 69. 5% għal 86. 7% rispettivament.
With 5 years follow-up, there were 86 (15.6%) progression events in the Glivec arm:
Waqt il- follow- up fil- 5 snin ta ’ wara, kien hemm 86 (15. 6%) eventi ta ’ avvanz fil- fergħa Glivec:
35 (6.3%) involving progression to accelerated phase/ blast crisis, 28 (5.1%) loss of MCyR, 14 (2.5%) loss of CHR or increase in WBC, and 9 (1.6%) CML unrelated deaths.
35 (6. 3%) li jinvolvu avvanz għall- Fażi aċċelerata/ blast crisis, 28 (5. 1%) telf ta ’ MCyR, 14 (2. 5%) telf ta ’ CHR jew żieda fil- WBC, u 9 (1. 6%) mwiet mhux relatati ma ’ CML.
In contrast, there were 155 (28.0%) events in the IFN+Ara-C arm, of which 128 occurred during first-line treatment with IFN+Ara-C.
B’ kuntrast, kien hemm 155 (28. 0%) eventi fil- fergħa IFN+Ara- C, li minnhom 128 seħħew waqt il- kura preferita b’ IFN+Ara- C.
The estimated rate of patients free of progression to accelerated phase or blast crisis at 60 months was significantly higher in the Glivec arm compared to the IFN arm (92.9% versus 86.2%, p < 0.001).
Ir- rata ta ’ pazjenti ħielsa minn avvanz għall- Fażi aċċelerata jew blast crisis fis- 60 xahar kien ogħla b’ mod sinifikanti mill- fergħa ta ’ Glivec imqabbel mal- fergħa ta ’ IFN (92. 9% versus 86. 2%, p < 0. 001).
The estimated rate of progression-free survival at 60 months was 83.2% in the Glivec arm and 64.1% in the control arm (p < 0.001).
Ir- rata ta ’ avvanz kull sena għall- dażi imgħaġġla jew blast crisis naqset maż- żmien bit- terapija u kienet anqas minn 1% kull sena fir- raba u ħames sena, Ir- rata stmata ta ’ soppravienza ħielsa minn avvanz fis - 60 xahar kienet 83. 2% fil- fergħa ta ’ Glivec u 64. 1% fil- fergħa tal- kontroll (p < 0. 001).
The yearly rates of progression of any type for Glivec also decreased over time.
Ir- rati annwali ta ’ avvanz ta ’ kull tip għal Glivec ukoll naqsu biż- żmien.
A total of 57 (10.3%) and 73 (13.2%) patients died in the Glivec and IFN+Ara-C groups, respectively.
Total ta ’ 57 (10. 3%) u 73 (13. 2%) ta ’ pazjenti mietu fil- gruppi ta ’ Glivec u IFN + Ara- C, rispettivament.
85.6% (82, 89) in the randomised Glivec and the IFN+Ara-C groups, respectively (p=0.049, log-rank test).
Fis- 60 xahar is- sopravivenza globali hija stmata 89. 4% (86, 92) vs 85. 6% (82, 89) fil - gruppi randomised Glivec u IFN + Ara- C, rispettivament (p=0. 049, test log- rank).
This time-to-event endpoint is strongly affected by the high crossover rate from IFN+Ara-C to Glivec.
Dan l- endpoint żmien- għall- event huwa effettwat bil- qawwa mill- qlib minn IFN+Ara- C għal Glivec.
The effect of Glivec treatment on survival in chronic phase, newly diagnosed CML has been further examined in a retrospective analysis of the above reported Glivec data with the primary data from another Phase III
L- effett ta ’ Glivec fuq sopravivenza fil- fażi kronika, CML li jkun għadu kif ġie dijanjostikat ġie eżaminat aktar f’ analiżi retrospettiva bid- dejta t’ hawn fuq li kienet rappurtata bi Glivec mad- dejta primarja minn studju ieħor ta ’ Fażi III b’ IFN+Ara- C (n=325) b’ reġimen identiku.
In this retrospective analysis, the superiority of Glivec over IFN+Ara-C in overall survival was demonstrated (p < 0.001); within 42 months, 47 (8.5%) Glivec patients and 63 (19.4%) IFN+Ara-C patients had died.
F’ din l- analiżi retrospettiva, is - superjorità ta ’ Glivec fuq IFN+Ara- C fis- sopravivenza globali kienet dimostrata (p < 0. 001); fi żmien 42 xahar, 47 (8. 5%) pazjenti fuq Glivec u 63 (19. 4%) pazjenti fuq IFN+Ara- C kienu mietu.
The degree of cytogenetic response and molecular response had a clear effect on long-term outcomes in patients on Glivec.
Il- grad ta ’ rispons ċitoġenetiku u rispons molekulari kellu effett ċar fuq il- konsegwenzi fit- tul f’ pazjenti fuq Glivec.
Whereas an estimated 97% (93%) of patients with CCyR (PCyR) at 12 months were free of progression to accelerated phase/ blast crisis at 60 months, only 81% of patients without MCyR at 12 months were free of progression to advanced CML at 60 months (p < 0.001 overall, p=0.20 between CCyR and PCyR).
Filwaqt li 97% (93%) tal- pazjenti b’ CCyR (PCyR) kienu stmati li kienu ħielsa minn avvanz fit- 12- il xahar għall- Fażi aċċelerata/ blast crisis fis- 60 xahar, 81% biss tal- pazjenti mingħajr MCyR fit- 12- il xahar kienu ħielsa minn avvanz għal CML fis- 60 xahar (p < 0. 001 globali, p=0. 20 bejn CCyR u PCyR).
For patients with CCyR and reduction in Bcr-Abl transcripts of at least 3 logarithms at 12 months, the probability of remaining free from progression to accelerated phase/ blast crisis was 100% at 60 months.
Għal pazjenti b’ CCyR u bi tnaqqis fit- transcripts Bcr- Abl ta ’ mill- anqas 3 logarithms fit- 12- il xahar, il- probabilità li l- pazjent jibqa ħieles minn avvanz għall- Fażi aċċelerata/ blast crisis kienet 100% fis- 60 xahar.
Similar findings were found based on a 18-months landmark analysis.
Sejbiet simili kienu evidenti minn analiżi landmark ta ’ 18- il xahar.
In this study, dose escalations were allowed from 400 mg daily to 600 mg daily, then from 600 mg daily to 800 mg daily.
F’ dan l- istudju, żiediet tad- doża tħallew minn 400 mg kuljum għal 600 mg kuljum, imbagħad minn 600 mg kuljum għal 800 mg kuljum.
After 42 months of follow-up, 11 patients experienced a confirmed loss (within 4 weeks) of their cytogenetic response.
Fl- 42 xahar follow- up ta ’ wara, 11- il pazjent kellhom telf konfermat (fi żmien 4 ġimgħat) minn meta kellhom rispons ċitoġenetiku.
Of these 11 patients, 4 patients escalated up to 800 mg daily, 2 of whom regained a cytogenetic response (1 partial and 1 complete, the latter also achieving a molecular response), while of the 7 patients who did not escalate the dose, only one regained a complete cytogenetic response.
Il- perċentwali ta ’ xi wħud mir -
The percentage of some adverse reactions was higher in the 40 patients in whom the dose was increased to 800 mg daily compared to the population of patients before dose increase (n=551).
16 reazzjonijiet avversi kien ogħla fl- 40 pazjent li kellhom id- doża miżjuda għall- 800 mg kuljum imqabbla mal- popolazzjoni tal- pazjenti qabel żdiedet id- doża (n=551).
The more frequent adverse reactions included gastrointestinal haemorrhages, conjunctivitis and elevation of transaminases or bilirubin.
Ir- reazzjonijiet avversi l- aktar frekwenti kienu jinkludu emmorraġiji gastro- intestinali, konġunktivite u żiediet fit- transaminases jew bilirubin.
Other adverse reactions were reported with lower or equal frequency.
Reazzjonijiet avversi oħrajn kienu rappurtati bl- istess frekwenza jew anqas.
Chronic phase, Interferon failure:
Il- fażi kronika, meta Interferon ma ħadimx:
532 adult patients were treated at a starting dose of 400 mg.
532 il- pazjent adult ġew kurati b’ doża tal- bidu ta ’ 400 mg.
The patients were distributed in three main categories: haematological failure (29%), cytogenetic failure (35%), or intolerance to interferon (36%).
Il- pazjenti ġew imqassma fi tliet kategoriji prinċipali: nuqqas ta ’ suċċess mill- aspett matolaġiku (29%), nuqqas ta ’ suċċess mill- aspett ċitoġenetiku (35%), jew inkella nuqqas ta ’ tolleranza għall - interferon (36%).
Patients had received a median of 14 months of prior IFN therapy at doses ≥ 25 x 106 IU/ week and were all in late chronic phase, with a median time from diagnosis of 32 months.
Il- pazjenti kienu kollha rċievew medjan ta ’ 14- il xahar ta ’ terapija b’ IFN minn qabel, f’ dożi ta ’ ≥ 25 x 106 IU/ ġimgħa u lkoll kienu f’ fażi kronika avanzata fiż- żmien, bi żmien medjan minn meta kienet saret id- dijanjosi, ta ’ 32 xahar.
The primary efficacy variable of the study was the rate of major cytogenetic response (complete plus partial response, 0 to 35% Ph+ metaphases in the bone marrow).
Il- fattur varjabbli ewlieni ta ’ l- effikaċja fl - istudju, kien ir- rata ta ’ rispons ċitoġenetiku maġġuri (rispons sħieħ u parzjali, 0 sa 35% ta ’ metafażijiet Ph+ fil- mudullun).
In this study 65% of the patients achieved a major cytogenetic response that was complete in 53% (confirmed 43%) of patients (Table 4).
F ’ dan l- istudju 65% tal- pazjenti kellhom rispons ċitoġenetiku maġġuri li kien komplet f ’ 53% (43% konfermati) tal- pazjenti (Tabella 4).
A complete haematological response was achieved in 95% of patients.
Rispons ematoloġiku sħiħ ntlaħaq f ’ 95% tal- pazjenti.
Accelerated phase:
Il- fażi aċċelerata: