qanastek/EMEA-V3 huggingface dataset:
monotherapy n=224
TMZ waħdu n=224
Infection, Herpes simplex, wound infection, pharyngitis, candidiasis oral
Infezzjoni, Herpes simplex, infezzjoni tal - ġerħa, farinġite, kandidijasi fil- ħalq
Infection, candidiasis oral
Infezzjoni, kandidijasi fil- ħalq
Herpes simplex, herpes zoster, influenza–like symptoms
Herpes simplex, herpes zoster, sintomi bħal ta ’ l- influwenza
Neutropenia, thrombocytopenia, lymphopenia, leukopenia
Newtropenja, tromboċitopenja, limfopenja, lewkopenja
Febril neutropenia, thrombocytopenia, anaemia, leukopenia
Newtropinja bid- deni, tromboċitopenja, anemija, lewkopenja
Uncommon:
7 Mhux komuni:
Febrile neutropenia, anaemia
Newtropinja bid- deni, anemija
Lymphopenia, petechiae
Limfopenja, petekje
Uncommon:
Disturbi fis- sistema endokrinarja Mhux komuni:
Metabolism and nutrition
Disturbi fil- metaboliżmu
Cushingoid disorders
Cushingoid u n- nutrizzjoni
Anorexia Hyperglycaemia, weight decreased Hypokalemia, alkaline phosphatase increased, weight increased
Anoressja Ipergliċemija, tnaqqis tal- piż Ipokalimja, żieda ta ’ alkaline phosphatase, żieda fil- piż
Anorexia Weight decreased Hyperglycaemia, weight increased
Anoressja Tnaqqis tal- piż Ipergliċemija, żieda fil- piż
Anxiety, emotional lability, insomnia
Ansjetà, burdati emozzjonali, nuqqas ta ’ rqad
Anxiety, depression, emotional lability, insomnia
Ansjetà, dipressjoni, burdati emozjonali, nuqqas ta ’ rqad
Agitation, apathy, behaviour disorder, depression, hallucination
Aġitazzjoni, apatija, disturbi fl- imġieba, dipressjoni, alluċinazzjoni
Hallucination, amnesia
Alluċinazzjoni, amneżija
7 Common:
Komuni:
Convulsions, consciousness decreased, somnolence, aphasia, balance impaired, dizziness, confusion, memory impairment, concentration impaired, neuropathy, paresthesia, speech disorder, tremor
Uġigħ ta ’ ras Konvulzjonijiet, tnaqqis tal- konxjetà, ngħas, afażja, telf ta ’ l- ekwilibriju, sturdament, konfużjoni, telf tal- memorja, telf tal- konċentrazzjoni, newropatija, parasteżija, ma jitkellmux tajjeb, tregħid
Hemiparesis, aphasia, balance impaired, somnolence, confusion, dizziness, memory impairment, concentration impaired, dysphasia, neurological disorder (NOS), neuropathy, peripheral neuropathy, paresthesia, speech disorder, tremor
Konvulżjonijiet, uġigħ ta ’ ras Emipareżi, afażia, telf ta ’ l - ekwilibriju, ngħas, konfużjoni, sturdament, telf tal- memorja, telf tal - konċentrazzjoni, disfażja, disturbi newroloġiċi (NOS), newropatija, newropatija periferali, parasteżija, ma jitkellmux tajjeb, tregħid
Status epilepticus, extrapyramidal disorder, hemiparesis, ataxia, cognition impaired, dysphasia, gait abnormal, hyperesthesia, hypoesthesia, neurological disorder (NOS), peripheral neuropathy
Status epilepticus, disturbi ekstrapiramidali, emipareżi, atassja, għarfien imxekkel, disfażja, andatura mhux normali, iperesteżija, ipoesteżija, disturbi newroloġiċi (NOS), newropatija periferali
Hemiplegia, ataxia, coordination abnormal, gait abnormal, hyperesthesia, sensory disturbance
Emipleġja, atassja, koordinament anormali, andatura mhux normali, iperesteżija, disturbi sensorjali
Vision blurred
Vista mċajpra
Visual field defect, vision blurred, diplopia
Difett fil- kamp viżiv, vista mċajpra, diplopja
Hemianopia, visual acuity reduced, vision disorder, visual field defect, eye pain
Ħemjanopja, il- vista ma tibqax ċara, disturbi viżwali, difett fil- kamp viżiv, uġigħ fl- għajnejn
Visual acuity reduced, eye pain, eyes dry
Il- vista ma tibqax ċara, uġigħ fl - għajnejn, għajnejn xotti
Hearing impairment
Is- smigħ jonqos
Hearing impairment, tinnitus
Is- smigħ jonqos, tisfir fil- widnejn
Otitis media, tinnitus, hyperacusis, earache
Otitis media, tisfir fil- widnejn, iperakużis, uġigħ fil- widnejn
Deafness, vertigo, earache
Telf tas- smigħ, vertigo, uġigħ fil - widnejn
Vascular disorders
Disturbi fil- qalb Mhux komuni Disturbi vaskulari
Palpitation
Palpitazzjonijiet
Common:
8 Komuni:
Haemorrhage, oedema, oedema leg
Emorraġġija, edima, edima fir- riġlejn
Haemorrhage, deep venous thrombosis, oedema leg
Emorraġġija, deep vein trombosis, edima fir- riġlejn
Cerebral haemorrhage, hypertension
Emorraġġija ċerebrali, pressjoni għolja
Embolism pulmonary, oedema, oedema peripheral
Emboliżmu fil- pulmun, edima, edima periferali
Dyspnoea, coughing
Qtugħ ta ’ nifs, sogħla
Pneumonia, upper respiratory infection, nasal congestion
Pulmonite, infezzjoni respiratorja tal- parti ta ’ fuq, imnieħer imblukkat
Pneumonia, sinusitis, upper respiratory infection, bronchitis
Pulmonite, sinusite, infezzjoni respiratorja tal- parti ta ’ fuq, bronkite
Constipation, nausea, vomiting
Stitikezza, tqallih, rimettar
Stomatitis, diarrhoea, abdominal pain, dyspepsia, dysphagia
Stomatite, dijarea, uġigħ addominali, dispepsja, disfaġja
Stomatitis, diarrhoea, dyspepsia, dysphagia, mouth dry
Stomatite, dijarea, dispepsja, disfaġja, ħalq xott
Abdominal distension, fecal incontinence, gastrointestinal disorder (NOS), gastroenteritis, haemorrhoids
Disturbi fil- ġilda u fit- tessuti ta ’ taħt il- ġilda
Skin and subcutaneous tissue disorders
Nefħa addominali, inkontinenza ta ’ l - ippurgar, disturbi gastro- intestinali (NOS), gastroenterite, emorrojdi
8 Very common:
Komuni ħafna:
Dermatitis, dry skin, erythema, pruritus
Dermatite, ġilda xotta, ħmura, ħakk
Dry skin, pruritus
Ġilda xotta, ħakk
Skin exfoliation, photosensitivity reaction, pigmentation abnormal
Ġilda titqaxxar, reazzjoni ta ’ sensitività għad- dawl, lewn tal- ġilda anormali
Erythema, pigmentation abnormal, sweating increased
Ħmura, lewn tal- ġilda anormali, żieda fl- għaraq
Musculoskeletal and connective tissue disorders Common:
Disturbi muskolu- skeletrali u tal- connective tissue Komuni:
Muscle weakness, arthralgia
Dgħjufija fil- muskoli, artralġja
Muscle weakness, arthralgia, musculoskeletal pain, myalgia
Dgħjufija fil- muskoli, artralġja, uġigħ muskolu- skeletrali, mijalġja
Myopathy, back pain, musculoskeletal pain, myalgia
Mijopatija, uġigħ fid- dahar, uġigħ muskolu- skeletrali, mijalġja
Myopathy, back pain
Mijopatija, uġigħ fid- dahar
Micturition frequency, urinary incontinence
Żieda fil- frekwenza ta ’ l- awrinar, inkontinenza ta ’ l- awrina
Urinary incontinence
Inkontinenza ta ’ l- awrina
Uncommon:
Uncommon:
Dysuria
Diżurja
Vaginal haemorrhage, menorrhagia, amenorrhea, vaginitis, breast pain
Emorraġġija vaġinali, menorraġja, amenorreja, vaġinite, uġigħ fis- sider
General disorders and administration site conditions Very common:
Disturbi ġenerali u kundizzjonijiet ta 'mnejn jingħata Komuni ħafna:
Allergic reaction, fever, radiation injury, face oedema, pain, taste perversion
Reazzjoni allerġika, deni, ħsara mir - radjazzjoni, edima tal- wiċċ, uġigħ, perverżjoni tat- togħma
Allergic reaction, fever, radiation injury, pain, taste perversion
Reazzjoni allerġika, deni, ħsara mir - radjazzjoni, uġigħ, perverżjoni tat - togħma
Uncommon:
9 Mhux komuni:
Asthenia, flushing, hot flushes, condition aggravated, rigors, tongue discolouration, parosmia, thirst
Astenja, isiru ruxxana, fwawar tas- sħana, il- kundizzjoni taggrava, tertir, l- ilsien jitlef lewnu, parosmja, għatx
Asthenia, face oedema, pain, condition aggravated, rigors, tooth disorder, taste perversion
Astenja, edima tal- wiċċ, uġigħ, il - kundizzjoni taggrava, tertir, disturbi tas- snien, perverżjoni tat- togħma
ALT increased
Żieda ta ’ ALT
Hepatic enzymes increased, Gamma GT increased, AST increased
Żieda ta ’ l- enzimi epatiċi, żieda ta ’ gamma GT, żieda ta ’ AST
*A patient who was randomised to the RT arm only, received TMZ + RT.
* Pazjent li kien randomised għal fergħa ta ’ RT biss, ingħata TMZ + RT.
Laboratory results
Riżultati tal- laboratorju
Myelosuppression (neutropenia and thrombocytopenia), which is known dose-limiting toxicity for most cytotoxic agents, including TMZ, was observed.
Majelosuppressjoni (newtropenija u tromboċitopenja), li hija magħrufa bħala tossiċità li tillimita d - doża għal ħafna sustanzi ċitotossiċi, inkluż TMZ, seħħet.
When laboratory abnormalities and adverse events were combined across concomitant and monotherapy treatment phases, Grade 3 or Grade 4 neutrophil abnormalities including neutropenic events were observed in 8% of the patients.
Meta anormalitajiet tal- laboratorju u effetti avversi kienu kumbinati bejn il- fażijiet b’ kura meta ingħataw flimkien u b’ dik meta ingħata waħdedha, anormalitajiet tan- newtrofili ta ’ Grad 3 jew Grad 4, inklużi effetti newtropeniċi dehru f’ 8% tal - pazjenti.
Grade 3 or Grade 4 thrombocyte abnormalities, including thrombocytopenic events were observed in 14% of the patients who received TMZ.
Anormalitajiet fit- tromboċiti ta ’ Grad 3 jew Grad 4, inklużi effetti tromboċitopeniċi deheru f’ 14% tal- pazjenti li ingħataw TMZ.
Recurrent or progressive malignant glioma
Glijoma malinna rekurrenti jew progressiva
These reactions were usually
Fi provi kliniċi, l- aktar effetti mhux mixtieqa relatati mal- kura li seħħew ta ’ spiss kienu disturbi gastro- intestinali, speċifikament tqallih (43%) u rimettar (36%).
9 Grade 1 or 2 (0 – 5 episodes of vomiting in 24 hours) and were either self-limiting or readily controlled with standard anti-emetic therapy.
Dawn ir- reazzjonijet kienu normalment Grad 1 jew 2 (0 – 5 episodji ta ’ rimettar f’ 24 siegħa) u jew waqfu waħidhom jew kienu kontrollati b’ terapija kontra t- tqallih standard.
The incidence of severe nausea and vomiting was 4%.
Il- frekwenza ta ’ tqallih sever u rimettar kienet 4%.
Table 5.
Tabella 5 tinkludi reazzjonjiet avversi li kienu rrappurtati fi provi kliniċi għall- glijoma malinna rikurrenti jew progressiva u wara t- tqegħid fis- suq ta ’ Temodal.
Adverse reactions in patients with recurrent or progressive malignant glioma Infections and infestations
Tabella 5: Reazzjonijiet avversi f’ pazjenti bi glijoma malinna rikurrenti jew progressiva
Opportunistic infections, including PCP
Infezzjonijiet opportunistiċi, inkluż PCP
Neutropenia or lymphopenia (grade 3-4), thrombocytopenia (grade 3-4)
Newtropenja jew limfopenja (grad 3- 4), tromboċitopenja (grad 3- 4)
Metabolism and nutrition disorders
Mhux komuni Disturbi fil- metaboliżmu u n- nutrizzjoni
Pancytopenia, anaemia (grade 3-4), leukopenia
Panċitopenja, anemija (grad 3- 4), lewkopenja
Anorexia Weight decrease
Telf tal- piż
Headache Somnolence, dizziness, paresthesia
Disturbi respiratorji, toraċiċi u medjastinali
Respiratory, thoracic and mediastinal disorders
Ngħas, sturdament, parasteżija
Vomiting, nausea, constipation Diarrhoea, abdominal pain, dyspepsia
Dijarea, uġigħ addominali, dispepsja
Rash, pruritus, alopecia Erythema multiforme, erythroderma, urticaria, exanthema
Raxx, ħakk, alopeċja Erythema multiforme, eritroderma, urtikarja, eksantema
Fatigue Fever, asthenia, rigors, malaise, pain, taste perversion Allergic reactions, including anaphylaxis, angioedema
Reazzjonijiet allerġiċi, inkluża anafilassi, anġjoedima
Grade 3 or 4 thrombocytopenia and neutropenia occurred in 19% and 17% respectively, of patients treated for malignant glioma.
Tromboċitopenja u newtropenja ta ’ Grad 3 jew 4 seħħew f’ 19% u 17% tal- pazjenti rispettivament, f’ pazjenti kkurati għal glioma malinna.
This led to hospitalisation and/or discontinuation of TMZ in 8% and 4%, respectively.
Minħabba f’ hekk kellhom jittieħdu l- isptar u/ jew kellu jitwaqqaf TMZ f’ 8% u 4%, rispettivament.
Myelosuppression was predictable (usually within the first few cycles, with the nadir between Day 21 and Day 28), and recovery was rapid, usually within 1-2 weeks.
Majelosuppressjoni setgħet tkun imbassra (normalment fl- ewwel ftit ċikli, bl- aktar punt baxx ma ’ Jum 21 u Jum 28), u l- irkupru kien mgħaġġel, normalment fi żmien 1- 2 ġimgħat.
No evidence of cumulative myelosuppression was observed.
Ma kienx hemm sinjali ta ’ majelosuppressjoni kumulattiva.
The presence of thrombocytopenia may increase the risk of bleeding, and the presence of neutropenia or leukopenia may increase the risk of infection.
It- tromboċitopenja żżid ir- riskju ta ’ emorraġġija, u meta jkun hemm newtropenija jew lewkopenija jkun hemm riskju akbar ta ’ infezzjoni.
Gender
Sess
In a population pharmacokinetics analysis of clinical trial experience there were 101 female and 169 male subjects for whom nadir neutrophil counts were available and 110 female and 174 male subjects for whom nadir platelet counts were available.
F’ analiżi bil- farmakokinetiċi ta’ popolazzjoni fl- esperjenza bi prova klinika kien hemm 101 mara u 169 raġel li għalihom il- valuri l- aktar baxxi tan- newtrofili kienu disponibbli u 110 mara u 174 raġel li għalihom il- valuri l- aktar baxxi tal- plejtlets kienu disponibbli.
There were higher rates of Grade 4 neutropenia (ANC < 0.5 x 109/l), 12% vs 5%, and thrombocytopenia (< 20 x 109/l), 9% vs 3%, in women vs men in the first cycle of therapy.
Kien hemm rati ogħla ta ’ newtropenja ta ’ Grad 4 (ANC < 0. 5 x 109/ l), 12% vs 5%, u tromboċitopenja (< 20 x 109/ l), 9% vs 3% fin- nisa vs l- irġiel fl- ewwel ċiklu tat- terapija.
In a 400 subject recurrent glioma data set, Grade 4 neutropenia occurred in 8% of female vs 4% of male subjects and Grade 4 thrombocytopenia in 8% of female vs 3% of male
F’ set ta ’ dejta għal glijoma b’ 400 individwu, newtropenja ta ’ Grad 4 seħħet fi 8% tan- nisa vs 4% ta ’ l- irġiel u tromboċitopenja ta ’ Grad 4 fi 8% tan- nisa vs 3% ta ’ l- irġiel fl- ewwel ċiklu tat- terapija.
In a study of 288 subjects with newly-diagnosed glioblastoma multiforme, Grade 4 neutropenia occurred in 3% of female vs 0% of male subjects and Grade 4 thrombocytopenia in 1% of female vs 0% of male subjects in the first cycle of therapy.
Fi studju b’ 288 individwu b’ glioblastoma multiforme li għada kif ġiet dijanjostikata, newtropinja ta ’ Grad 4 seħħet f’ 3% tan- nisa vs 0% ta ’ l- irġiel u tromboċitopenja ta ’ Grad 4 seħħet f’ 1% tan- nisa vs 0% ta ’ l- irġiel fl- ewwel ċiklu tat- terapija.
Post-Marketing Experience
Esperjenza ta ’ wara t- tqegħid fis- suq
Antineoplastic agents, and notably alkylating agents, have been associated with a potential risk of myelodysplastic syndrome (MDS) and secondary malignancies, including leukaemia.
Aġenti anti- neoplastiċi, u l- aktar alkylating agents, kienu assoċjati ma ’ riskju potenzjali ta ’ sindrome majelodisplastiku (MDS) u tumuri malinni sekondarji, li jinkludu lewkimja.
Very rare cases of MDS and secondary malignancies, including myeloid leukaemia have been reported in patients treated with regimens that included TMZ.
Każijiet rari ħafna ta ’ MDS u tumuri malinni sekondarji, li jinkludu lewkimja majelojde kienu rrapurtati f’ pazjenti kkurati b’ korsijiet li kienu jinkludu TMZ.
Prolonged pancytopenia, which may result in aplastic anaemia has been reported very rarely.
Panċitopenja mtawwla, li tista ’ sseħħ b’ anemija aplastika kienet rrapurtata b’ mod rari ħafna.
Cases of toxic epidermal necrolysis and Stevens-Johnson syndrome have been reported very rarely.
Każijiet ta ’ nekrożi tossika tal- ġilda u sindrome ta ’ Stevens- Johnson kienu rrappurtati rari ħafna.
Cases of interstitial pneumonitis/pneumonitis have been reported very rarely.
Każijiet ta ’ pnewmonite fl- interstizzju/ pnewmonite kienu rrappurtati rari ħafna.
Doses of 500, 750, 1,000, and 1,250 mg/m2 (total dose per cycle over 5 days) have been evaluated clinically in patients.
Dożi ta ’ 500, 750, 1, 000, u 1, 250 mg/ m2 (doża totali kull ċiklu matul 5 tijiem) ġew evalwati klinikament f 'pazjenti.
Dose-limiting toxicity was haematological and was reported with any dose but is expected to be more severe at higher doses.
Kien hemm limitazzjoni tad- doża minħabba tossiċita` ħematoloġika li kienet irrappurtata ma ’ kwalunkwe doża iżda hu mistenni li tkun aktar serja b’ dożi aktar qawwija.
An overdose of 10,000 mg (total dose in a single cycle, over 5 days) was taken by one patient and the adverse reactions reported were pancytopenia, pyrexia, multi- organ failure and death.
Doża eċċessiva ta ’ 10, 000 mg (doża totali f’ ċiklu wieħed, matul 5 tijiem) ittieħdet minn pazjent u r - reazzjonijiet avversi rrappurtati kienu panċitopenja, deni, kollass ta ’ diversi organi u mewt.
There are reports of patients who have taken the recommended dose for more than 5 days of treatment (up to 64 days) with adverse events reported including bone marrow suppression, with or without infection, in some cases severe and prolonged and resulting in death.
Hemm rapporti ta ’ pazjenti li ħadu d- doża rrakkomandata għal aktar mill- 5 tijiem tat- trattament (sa 64 jum) b’ effetti avversi rrappurtati li jinkludu soppressjoni tal- mudullun, b’ infezzjoni jew mingħajr
In the event of an overdose, haematological evaluation is needed.
11 infezzjoni, f’ xi każijiet li kienu serji u fit- tul u li wasslu għall- mewt.
Supportive measures should be provided as necessary.
Miżuri ta 'appoġġ għandhom ikunu pprovduti kif meħtieġ.
L01A X03
Aġenti antineoplastiċi – alkylating agents oħra, kodiċi ATC L01A X03
Temozolomide is a triazene, which undergoes rapid chemical conversion at physiologic pH to the active monomethyl triazenoimidazole carboxamide (MTIC).
Temozolomide huwa triazene, li fil- pH fiżjoloġiku jinbidel malajr f’ sustanza attiva monomethyl triazenoimidazole carboxamide (MTIC).
The cytotoxicity of MTIC is thought to be due primarily to alkylation at the O6 position of guanine with additional alkylation also occurring at the N7 position.
Huwa maħsub li ċ- ċitotossiċità ta ’ monomethyl triazenoimidazole carboxamide (MTIC) hija primarjament minħabba l- alkylation f’ pożizzjoni O6 ta ’ guanine, b’ alkylation addizzjonali li sseħħ ukoll f’ pożizzjoni N7.
Cytotoxic lesions that develop subsequently are thought to involve aberrant repair of the methyl adduct.
Ġrieħi ċitotossiċi li jiżviluppaw sussegwentement huma maħsuba li jinvolvu t- tiswija anormali tal- methyl adduct.
A total of 573 patients were randomised to receive either TMZ + RT (n=287) or RT alone (n=286).
Glioblastoma multiforme li tkun għada kif ġiet dijanjostikata Total ta ’ 573 pazjent ġew randomised biex jirċievu jew TMZ + RT (n=287) jew RT waħdu (n=286).
Patients in the TMZ + RT arm received concomitant TMZ (75 mg/m2) once daily, starting the first day of RT until the last day of RT, for 42 days (with a maximum of 49 days).
Il- pazjenti fil- fergħa ta ’ TMZ + RT irċevew flimkien TMZ (75 mg/ m2) darba kuljum, bdew fl- ewwel jum ta ’ RT sa l- aħħar jum ta ’ RT għal 42 jum (sa mhux aktar minn 49 jum).
This was followed by monotherapy TMZ (150 - 200 mg/m2) on Days 1 - 5 of every 28-day cycle for up to 6 cycles, starting 4 weeks after the end of RT.
Dan kien segwit b’ monoterapija ta ’ TMZ (150 – 200 mg/ m2) f’ Jiem 1 – 5 ta ’ kull ċiklu ta ’ 28 jum sa 6 ċikli, bdew 4 ġimgħat wara li ntemmet r- RT.
Patients in the control arm received RT only.
Pazjenti fil- fergħa tal- kontroll ingħataw RT biss.
Pneumocystis carinii pneumonia (PCP) prophylaxis was required during RT and combined TMZ therapy.
Terapija biex tilqa għall- pulmonite b’ Pneumocystis carinii (PCP) kienet meħtieġa waqt it- terapija bl- RT u b’ dik ikkombinata ma ’ TMZ.
TMZ was administered as salvage therapy in the follow-up phase in 161 patients of the 282 (57%) in the RT alone arm, and 62 patients of the 277 (22%) in the TMZ + RT arm.
TMZ kien mogħti bħala terapija tas- salvataġġ fil- fażi ta ’ follow- up f’ 161 pazjent mill- 282 (57%) fil - fergħa b’ RT waħdu, u f’ 62 pazjent mill- 277 (22%) fil- fergħa ta ’ TMZ + RT.
11 The hazard ratio (HR) for overall survival was 1.59 (95% CI for HR=1.33 -1.91) with a log-rank p < 0.0001 in favour of the TMZ arm.
Il- proporzjon tal- periklu (HR) għas- sopravivenza ġenerali kienet ta ’ 1. 59 (95% CI għal HR=1. 33 - 1. 91) b’ log rank p < 0. 0001 favur il- fergħa ta ’ TMZ.
The estimated probability of surviving 2 years or more (26% vs 10%) is higher for the RT + TMZ arm.
Il- probabilità stmata li jkun hemm sopravivenza ta ’ sentejn jew aktar (26% vs 10%) hija ogħla għall- fergħa ta ’ RT + TMZ.
The addition of concomitant TMZ to RT, followed by TMZ monotherapy in the treatment of patients with newly-diagnosed glioblastoma multiforme demonstrated a statistically significant improvement in overall survival (OS) compared with RT alone (Figure 1).
Iż- żieda ta ’ TMZ flimkien ma ’ RT, segwit b’ TMZ waħdu fil- kura ta’ pazjenti f’ glioblastoma multiforme li tkun għada kif ġiet dijanjostikata wasslet għal titjib fis- sopravivenza ġenerali (OS) b’ mod statistikament sinifikanti meta mqabbel ma ’ RT waħidha (Figura 1).
Kaplan-Meier curves for overall survival (intent-to-treat population)
Kurvi Kaplan- Meier għas- sopravivenza ġenerali (popolazzjoni intent- to- treat)
The results from the trial were not consistent in the subgroup of patients with a poor performance status (WHO PS=2, n=70), where overall survival and time to progression were similar in both arms.
12 Ir- riżultati mill- prova ma kienux konsistenti fis- sottogrupp ta ’ pazjenti bi statut ta ’ prestazzjoni dgħajjef (WHO PS=2, n=70), fejn is- sopravivenza ġenerali u ż- żmien biex javvanzaw kienu simili fiż - żewġ fergħat.
However, no unacceptable risks appear to be present in this patient group.
Madankollu, ma jidhirx li hemm xi riskji li ma jistgħux jiġu aċċettati f’ dan is- sottogrupp ta ’ pazjenti.
Recurrent or progressive malignant glioma
Glijoma malinna rikurrenti jew progressiva
Data on clinical efficacy in patients with glioblastoma multiforme (Karnofsky performance status [KPS] ≥ 70), progressive or recurrent after surgery and RT, were based on two clinical trials with oral TMZ.
Dejta dwar l- effikaċja klinika f’ pazjenti b’ glioblastoma multiforme (Statut tal- prestazzjoni Karnofsky [KPS] ≥ 70), progressiva jew rikurrenti wara operazzjoni jew RT, kienet ibbażata fuq żewġ provi kliniċi b’ TMZ orali.
One was a non-comparative trial in 138 patients (29% received prior chemotherapy), and the other was a randomised active-controlled trial of TMZ vs procarbazine in a total of 225 patients (67% received prior treatment with nitrosourea based chemotherapy).
Waħda kienet prova mhux komparattiva f’ 138 pazjent (29% kienu rċevew il - kemoterapija qabel), u l- oħra kienet prova randomized kontrollata b’ mod attiv ta ’ TMZ vs procarbazine f’ total ta ’ 225 pazjent (67% kienu rċivew trattament qabel bil- kemoterapija bbażata fuq nitrosourea).
In both trials, the primary endpoint was progression-free survival (PFS) defined by MRI scans or neurological worsening.
Fiż- żewġ provi, il- fini primarju kien is- sopravivenza mingħajr progressjoni (PFS) kif definita minn skans ta ’ MRI jew mis- sistema newroloġika li tmur għall- agħar.
In the non- comparative trial, the PFS at 6 months was 19%, the median progression-free survival was 2.1 months, and the median overall survival 5.4 months.
Fl- istudju mhux komparattiv, il- PFS wara 6 xhur kien ta ’ 19%, is- sopravivenza mingħajr progressjoni medjana kienet ta ’ 2. 1. xhur, u l - medjan tas- sopravivenza totali kien ta ’ 5. 4 xhur.
The objective response rate (ORR) based on MRI scans was 8%.
Ir- rata ta ’ rispons oġġettiv (ORR) ibbażata fuq skans ta ’ MRI kienet ta ’ 8%.
In the randomised active-controlled trial, the PFS at 6 months was significantly greater for TMZ than for procarbazine (21% vs 8%, respectively – chi-square p = 0.008) with median PFS of 2.89 and 1.88 months respectively (log rank p = 0.0063).
Fil- prova randomised ikkontrollata b’ mod attiv, l- PFS ma ’ 6 xhur kien akbar b’ mod sinifikanti għal TMZ milli għal procarbazine (21% vs 8%, rispettivament – chi- square p = 0. 008) bil- PFS medjan ta ’ 2. 89 u 1. 88 xhur rispettivament (log rank p = 0. 0063).
The median survival was 7.34 and 5.66 months for TMZ and procarbazine, respectively (log rank p = 0.33).
Is- sopravivenza medjana kienet ta ’ 7. 34 u 5. 66 xhur għal TMZ u procarbazine, rispettivament (log rank p = 0. 33).
At 6 months, the fraction of surviving patients was significantly higher in the TMZ arm (60%) compared with the procarbazine arm (44%) (chi-square p = 0.019).
Mas- 6 xhur, il- porzjon tal - pazjenti li baqgħu ħajjin kien ogħla b’ mod sinifikanti fil- fergħa ta ’ TMZ (60%) meta mqabbel mal - fergħa ta ’ procarbazine (44%) (chi- square p = 0. 019).
In patients with prior chemotherapy a benefit was indicated in those with a KPS ≥ 80.
F’ pazjenti li ngħataw il- kemoterapija qabel, il - benefiċċju kien indikat f’ dawk b’ KPS ta ’ ≥80.
Data on time to worsening of neurological status favoured TMZ over procarbazine as did data on time to worsening of performance status (decrease to a KPS of < 70 or a decrease by at least 30 points).
Tagħrif dwar iż- żmien meta l- istat newroloġiku mar għall- agħar iffavorixxa TMZ fuq procarbazine, kif għamel it- tagħrif dwar iż- żmien meta l- istatut ta ’ prestazzjoni mar għall- agħar (tnaqqis għal KPS ta ’ < 70 jew tnaqqis b’ mill- inqas 30 punt).
The median times to progression in these endpoints ranged from 0.7 to 2.1 months longer for TMZ than for procarbazine (log rank p = < 0.01 to 0.03).
Iż- żminijiet medjani għall- progressjoni f’ dawn l- endpoints varja minn 0. 7 sa 2. 1 xhur aktar għal TMZ milli għal procarbazine (log rank p = < 0. 01 sa 0. 03).
12 Recurrent anaplastic astrocytoma
Astroċitoma anaplastika rikurrenti
In a multicentre, prospective phase II trial evaluating the safety and efficacy of oral TMZ in the treatment of patients with anaplastic astrocytoma at first relapse, the 6 month PFS was 46%.
Fi prova multiċentrika, prospettiva ta ’ fażi II li evalwat is- sigurtà u l- effikaċja ta ’ TMZ orali fit - trattament ta ’ pazjenti b’ astroċitoma anaplastika wara l- ewwel rikaduta, wara 6 xhur il- PFS kienet ta ’ 46%.
The median PFS was 5.4 months.
Il- PFS medjana kienet ta ’ 5. 4 xhur.
Median overall survival was 14.6 months.
Il- medjan tas- sopravivenza totali kien ta ’ 14. 6 xhur.
Response rate, based on the central reviewer assessment, was 35% (13 CR and 43 PR) for the intent-to-treat population (ITT) n=162.
Ir- rata ta ’ rispons, ibbażata fuq il- valutazzjoni tal- verifikatur ċentrali, kienet ta ’ 35% (13 CR u 43 PR) għall - popolazzjoni intent- to- treat (ITT) n=162.
In 43 patients stable disease was reported.
Fi 43 pazjent, mard stabbli kien irrappurtat.
The 6-month event-free survival for the ITT population was 44% with a median event-free survival of 4.6 months, which was similar to the results for the progression-free survival.
Is- sopravivenza mingħajr eventi wara 6 xhur għall- popolazzjoni ITT kienet ta ’ 44% b’ medjan ta ’ sopravivenza mingħajr eventi ta ’ 4. 6 xhur, li kienet tixbah lir- riżultati tas- sopravivenza mingħajr progressjoni.
For the eligible histology population, the efficacy results were similar.
Għall- popolazzjoni eliġibbli għall- ħistoloġija, ir- riżultati ta ’ l- effikaċja kienu simili.
Achieving a radiological objective response or maintaining progression-free status was strongly associated with maintained or improved quality of life.
Li jintlaħaq rispons oġġettiv radjuloġiku jew li l- istat mingħajr progressjoni jinżamm, kien assoċjat ħafna ma ’ kemm inżammet jew tjiebet il - kwalità tal- ħajja.
Oral TMZ has been studied in paediatric patients (age 3-18 years) with recurrent brainstem glioma or recurrent high grade astrocytoma, in a regimen administered daily for 5 days every 28 days.
TMZ orali kien studjat f’ pazjenti pedjatriċi (età 3- 18- il sena) bi brainstem glioma rikurrenti jew astroċitoma rikurrenti ta ’ grad għoli, f’ kors mogħti kuljum għal 5 ijiem kull 28 jum.
Tolerance to TMZ is similar to adults.
It- tolleranza għal - TMZ kienet simili għall- adulti.
TMZ is spontaneously hydrolyzed at physiologic pH primarily to the active species, 3-methyl-(triazen- 1-yl)imidazole-4-carboxamide (MTIC).
TMZ jkun idrolizzat b’ mod spontanju fil- pH fiżjoloġiku għall- ispeċi attivi, 3- methyl - (triazen- 1- yl) imidazole- 4- carboxamide (MTIC).
MTIC is spontaneously hydrolyzed to 5-amino-imidazole-4- carboxamide (AIC), a known intermediate in purine and nucleic acid biosynthesis, and to methylhydrazine, which is believed to be the active alkylating species.
MTIC jkun idrolizzat b’ mod spontanju għal 5- amino- imidazole- 4- carboxamide (AIC), intermedju mgħaruf fil- bijosintesi tal- purini u aċidi
The cytotoxicity of MTIC is thought to be primarily due to alkylation of DNA mainly at the O6 and N7 positions of guanine.
Iċ- ċitotossiċità ta ’ MTIC huwa maħsub li ġejja primarjament mill- alkylation ta ’ DNA l- aktar fil- pożizzjonijiet O6 u N7 ta ’ gwanin.
Relative to the AUC of TMZ, the exposure to MTIC and AIC is ~ 2.4% and 23%, respectively.
L- esponiment għal MTIC u AIC relattiv għall- AUC ta ’ TMZ huwa ~ 2. 4% u 23%, rispettivament.
In vivo, the t1/2 of MTIC was similar to that of TMZ, 1.8 hr.
In vivo it- t1/ 2 ta ’ MTIC kien simili għal dak ta ’ TMZ, 1. 8 hr.
After oral administration to adult patients, TMZ is absorbed rapidely, with peak concentrations reached as early as 20 minutes post-administration (mean time between 0.5 and 1.5 hours).
Wara l- għotja orali lill- pazjenti adulti, TMZ jiġi assorbit malajr, bl- ogħla konċentrazzjonijiet jintlaħqu minn kmieni sa 20 minuta wara li jkun ingħata (medja tal- ħin bejn 0. 5 u 1. 5 sigħat).
After oral administration of 14C-labelled TMZ, mean faecal excretion of 14C over 7 days post-dose was 0.8% indicationg complete absorption.
Wara li jingħata mill- ħalq, TMZ tikkettat bis- 14C, il- medja ta ’ l- ammont ta ’ 14C fl- ippurgar ‘ l fuq minn 7 ijiem wara d - doża kienet 0. 8% li tindika assorbiment komplet.
TMZ demonstrates low protein binding (10% to 20%), and thus it is not expected to interact with highly protein-bound substances.
TMZ jeħel b’ mod ħafif mal- proteini (10% sa 20%), u għalhekk mhux mistenni li jinteraġixxi ma ’ sustanzi li jeħlu ħafna mal- proteini.
PET studies in humans and preclinical data suggest that TMZ crosses the blood-brain barrier rapidly and is present in the CSF.
Studji PET fil- bniedem u dejta ta’ qabel l- użu kliniku jindikaw li TMZ jaqsam malajr mill- barriera ta ’ bejn id- demm u l- moħħ u jinstab fis- CSF.
CSF penetration was confirmed in one patient; CSF exposure based on AUC of TMZ was approximately 30% of that in plasma, which is consistent with animal data.
Il- fatt li jippenetra fis- CSF kien konfermat f’ pazjent wieħed; l- esponiment għal CSF ibbażata fuq l- AUC ta ’ TMZ kien ta ’ madwar 30% ta ’ dik fil- plażma, li huwa konsistenti mad- dejta mill- annimali.
The half-life (t1/2) in plasma is approximately 1.8 hours.
Il- half- life (t1/ 2) fil- plażma hija ta ’ madwar 1. 8 sigħat.
The major route of 14C elimination is renal.
Il- mod ewlieni ta ’ l- eliminazzjoni ta ’ 14C huwa dak renali.
Following oral administration, approximately 5% to 10% of the dose is recovered unchanged in the urine over 24 hours, and the remainder excreted as temozolomide acid, 5-aminoimidazole-4- carboxamide (AIC) or unidentified polar metabolites.
Wara għotja orali, madwar 5% sa 10% tad- doża tiġi rkuprata mhux mibdula mill- awrina fuq 24 siegħa, u l- bqijja eskretat bħala aċidu temozolomide, 5- aminoimidazole- 4- carboxamide (AIC) jew metaboli polari li ma ġewx identifikati.
Plasma concentrations increase in a dose-related manner.
Il- konċentrazzjonijiet tal- plażma jiżdiedu b’ mod skond id- doża.
Plasma clearance, volume of distribution and half-life are independent of dose.
It- tneħħija tal- plażma, il- volum tad - distribuzzjoni u l- half- life huma indipendenti mid- doża.
13 Analysis of population-based pharmacokinetics of TMZ revealed that plasma TMZ clearance was independent of age, renal function or tobacco use.
Analiżi tal- farmakokinetika ta ’ TMZ ibbażata fuq il- popolazzjoni wrew li t- tneħħija mill- plażma ta ’ TMZ kienet indipendenti mill- età, funzjoni tal- kliewi jew l- użu tat- tabakk.
In a separate pharmacokinetic study, plasma pharmacokinetic profiles in patients with mild to moderate hepatic impairment were similar to those observed in patients with normal hepatic function.
Fi studju farmakokinetiku separat, il- profili farmakokinetiċi tal- plażma f’ pazjenti b’ indeboliment tal- fwied minn ħafifa sa moderata kienu jixbhu lil dawk osservati f’ pazjenti b’ funzjoni tal- fwied normali.
Paediatric patients had a higher AUC than adult patients; however, the maximum tolerated dose (MTD) was 1,000 mg/m2 per cycle both in children and in adults.
Pazjenti pedjatriċi kellhom AUC ogħla minn dak ta ’ pazjenti adulti; madankollu, id- doża massima ttollerata (MTD) kienet ta ’ 1, 000 mg/ m2 kull ċiklu kemm fit- tfal u kemm fl- adulti.
Single-cycle (5-day dosing, 23 days non-treatment), 3- and 6-cycle toxicity studies were conducted in rats and dogs.
Studi dwar it- tossiċità fuq ċiklu wieħed (dożaġġ ta ’ 5 ijiem, 23 jum mingħajr trattament), 3 - u 6- ċikli kienu magħmula fuq firien u klieb.
The primary targets of toxicity included the bone marrow, lymphoreticular system, testes, the gastrointestinal tract and, at higher doses, which were lethal to 60% to 100% of rats and dogs tested, degeneration of the retina occurred.
It- targits primarji tat- tossiċità inkludew il- mudullun, is- sistema limforetikulari, it- testikoli u l- apparat gastro- intestinali u, f’ dożi aktar qawwija, li kkaġunaw il- mewt lil 60% sa 100% tal- firien u l- klieb ittestjati, seħħet deġenerazzjoni tar- retina.
Most of the toxicity showed evidence of reversibility, except for adverse events on the male reproductive system and retinal degeneration.
Kien hemm evidenza li l- biċċa l- kbira tat- tossiċità kienet riversibbli, ħlief f’ eventi avversi fis- sistema riproduttiva ta ’ l- irġiel u fid- deġenerazzjoni tar- retina.
However, because the doses implicated in retinal degeneration were in the lethal dose range, and no comparable effect has been observed in clinical studies, this finding was not considered to have clinical relevance.
Madankollu, minħabba li d- dożi implikati fid- deġenerazzjoni tar- retina kienu fil- medda tad- doża li tikkaġuna l- mewt, u l- ebda effett komparabbli ma kien osservat fi studji kliniċi, din is- sejba ma kinetx ikkunsidrata li għandha rilevanza klinika.
TMZ is an embryotoxic, teratogenic and genotoxic alkylating agent.
TMZ huwa aġent alkylating embrijotossiku, teratoġeniku, u ġinotossiku.
TMZ is more toxic to the rat and dog than to humans, and the clinical dose approximates the minimum lethal dose in rats and dogs.
TMZ huwa aktar tossiku għall- firien u għall- klieb milli għall- bnedmin, u d- doża klinika tqarreb lejn id- doża minima li tikkaġuna l- mewt fil- firien u fil- klieb.
Dose- related reductions in leukocytes and platelets appear to be sensitive indicators of toxicity.
It- tnaqqis fil- lewkoċiti u fil- plejtlets relatat mad- doża jidher li 14 huwa indikatur sensittiv tat- tossiċità.
A variety of neoplasms, including mammary carcinomas, keratocanthoma of the skin and basal cell adenoma were observed in the 6-cycle rat study while no tumours or pre-neoplastic changes were evident in dog studies.
Varjetà ta ’ neoplażmi, li jinkudu karċinomi mammarji, keratokantoma tal- ġilda u basal cell adenoma kienu osservati fi studju ta ’ 6- ċikli fuq il- firien, filwaqt li l- ebda tumuri jew tibdil pri- neoplastiku ma kien evidenti fi studji fuq il- klieb.
Rats appear to be particularly sensitive to oncogenic effects of TMZ, with the occurrence of first tumours within 3 months of initiating dosing.
Il- firien jidhru li huma partikularment sensittivi għall- effetti onkoġeniċi ta ’ TMZ, bl- ewwel tumuri li jseħħu fi żmien 3- xhur mill- bidu tad- dożaġġ.
This latency period is very short even for an alkylating agent.
Il- perijodu ta ’ latency huwa qasir ħafna, anke għal alkylating agent.
Results of the Ames/salmonella and Human Peripheral Blood Lymphocyte (HPBL) chromosome aberration tests showed a positive mutagenicity response.
Ir- riżultati ta ’ chromosome aberration tests ta ’ l- Ames/ salmonella u l- Limfoċit tad- Demm Periferali Uman (HPBL) urew rispons pożittiv għall- mutaġeniċità.
Capsule content: anhydrous lactose, colloidal anhydrous silica, sodium starch glycolate type A, tartaric acid, stearic acid.
Kontenut tal- kapsula: anhydrous lactose, colloidal anhydrous silica, sodium starch glycolate tip A, tartaric acid, stearic acid.
Capsule shell: gelatin, titanium dioxide (E 171), sodium laurilsulfate, yellow iron oxide (E 172), indigo carmine (E 132),
Qoxra tal- kapsula: gelatin, titanium dioxide (E 171), sodium lauril sulfate, yellow iron oxide (E 172), indigo carmin (E 132),
Printing ink: shellac, propylene glycol, purified water, ammonium hydroxide, potassium hydroxide, black iron oxide (E 172).
Stampar: shellac, propylene glycol, ilma purifikat, ammonium hydroxide, potassium hydroxide, black iron oxide (E 172).
Store in the original bottle in order to protect from moisture.
Taħżinx f’ temperatura ’ l fuq minn 30°C Aħżen fil- flixkun oriġinali sabiex tilqa mill- umdità.
Type I amber glass bottles with polypropylene child-resistant closures containing 5 -or 20 hard capsules.
Fliexken tal- ħġieġ kannella jagħti fl- oranġjo tat- Tip I b’ għeluq ta ’ polypropylene li huma reżistenti għat- tfal u li fihom 5- jew 20 kapsula iebsa.
The carton contains one bottle.
Il- kartuna fiha flixkun wieħed.
6.6 Special precautions for disposal and other handling
15 6. 6 Prekawzjonijiet speċjali li għandhom jittieħdu meta jintrema u għal immaniġġjar ieħor
Capsules should not be opened.
Il- kapsuli m’ għandhomx jinfetħu.
If a capsule becomes damaged, contact of the powder contents with skin or mucous membrane must be avoided.
Jekk il- kapsula tiġrilha l- ħsara, il- kuntatt tat- trab li jkun fiha mal - ġilda jew mal- membrani mukużi għandu jiġi evitat.
If Temodal comes into contact with skin or mucosa, it should be washed immediately and thoroughly with soap and water.
Jekk Temodal jiġi f’ kuntatt mal- ġilda jew mal - mukuża, għandu jiġi maħsul mill- ewwel u sew bis- sapun u bl- ilma.
Patients should be advised to keep capsules out of the reach and sight of children, preferably in a locked cupboard.
Il- pazjenti għandhom jingħataw parir bex iżommu l- kapsuli fejn ma jintlaħqux u fejn ma jidhrux mit- tfal, l - aħjar f’ armarju maqful.
Accidental ingestion can be lethal for children.
Jekk jibilgħuh b’ mod aċċidentali jista ’ joqtolhom.
Date of last renewal:
26 ta ’ Jannar, 1999 Data ta ’ meta ġiet imġedda l- aħħar:
26 January 2009
26 ta ’ Jannar, 2009
15 Detailed information on this medicinal product is available on the website of the European Medicines Agency (EMEA) http://www.emea.europa.eu/
Informazzjoni dettaljata dwar dan il- prodott tinsab fuq il- website ta ’ l- Aġenzija Ewropeja dwar il- Mediċini (EMEA) http: // www. emea. europa. eu /
Temodal 20 mg hard capsules
Kapsuli iebsin Temodal 20 mg
Each hard capsule contains 20 mg temozolomide.
Kull kapsula iebsa fiha 20 mg ta ’ temozolomide.
Each hard capsule contains 182.2 mg of anhydrous lactose.
Kull kapsla iebsa fiha 182. 2 mg anhydrous lactose.
The hard capsules have an opaque white body, an opaque yellow cap, and are imprinted with black ink.
Il- kapsuli iebsin għandhom naħa bajda opaka, b’ għatu opak isfar, u ttimbrati b’ inka sewda.
The cap is imprinted with “Temodal”.
L- għatu ttimbrat b ’ ” Temodal ”.
The body is imprinted with "20 mg", the Schering-Plough logo and two stripes.
In- naħa l- oħra ttimbrata b ’ ” 20 mg ”, il- logo ta ’ Schering- Plough u żewġ strippi.
Concomitant phase TMZ is administered orally at a dose of 75 mg/m2 daily for 42 days concomitant with focal radiotherapy (60 Gy administered in 30 fractions).
TMZ jingħata b’ mod orali b’ doża ta ’ 75 mg/ m2 kuljum għal 42 jum flimkien ma ’ radjuterapija fokali (60 GY mogħtija fi 30 frazzjonijiet).
- thrombocyte count ≥ 100 x 109/l
għadd tat- tromboċiti ≥ 100 x 109/ l
< 0.5 x 109/l
≥ 0. 5 u < 1. 5 x 10 / l < 10 x 109/ l
< 10 x 109/l
≥ 10 u < 100 x 109/ l
CTC Gr ade 3 or 4
CTC Grad 3 u 4
Treatment with concomitant TMZ can be continued when all of the following conditions are met: absolute neutrophil count ≥ 1.5 x 109/l; thrombocyte count ≥ 100 x 109/l; CTC non-haematological toxicity ≤ Grade 1 (except for alopecia, nausea, vomiting).
Il- kura b’ TMZ mogħti b’ mod konkomitanti tista ’ titkompla meta dawn il- kundizzjonijiet kollha jkunu jgħoddu: għadd assolut tan- newtrofili ≥ 1. 5 x 109/ l; għadd tat- tromboċiti ≥ 100 x 109/ l; tossiċità mhux ħematoloġika CTC ta ’ ≤ Grad 1 (ħlief għal alopeċja, tqallih, rimettar).
Dose in Cycle 1 (monotherapy) is 150 mg/m2 once daily for 5 days followed by 23 days without treatment.
Id- doża f’ Ċiklu 1 (monoterapija) huwa 150 mg/ m2 darba kuljum għal 5 tijiem segwit b’ 23 jum mingħajr kura.
At the start of Cycle 2, the dose is escalated to 200 mg/m2 if the CTC non- haematological toxicity for Cycle 1 is Grade ≤ 2 (except for alopecia, nausea and vomiting), absolute neutrophil count (ANC) is ≥ 1.5 x 109/l, and the thrombocyte count is ≥ 100 x 109/l.
Fil- bidu ta ’ Ċiklu 2, id- doża tiżdied għal 200 mg/ m2 jekk it- tossiċità mhux ħematoloġika CTC għal Ċiklu 1 huwa Grad ≤ 2 (ħlief għal alopeċja, tqallih u rimettar), jekk l - għadd assolut tan- newtrofili (ANC) jkun ≥ 1. 5 x 109/ l, u l- għadd tat- tromboċiti jkun ≥ 100 x 109/ l.
Once escalated, the dose remains at 200 mg/m2 per day for the first 5 days of each subsequent cycle except if toxicity occurs.
Ladarba d- doża tkun ġiet miżjuda, tinżamm għal 200 mg/ m2 kuljum fl- ewwel 5 tijiem ta ’ kull ċiklu li jkun imiss ħlief jekk isseħħ tossiċità.
2.
Tabella 2.
TMZ dose
Livell tad- doża
TMZ dose levels for monotherapy treatment Remarks
Doża ta ’ TMZ (mg/ m2/ jum)
(mg/m2/day)
Kummenti
18 Table 3.
18 Tabella 3.
TMZ dose levels are l isted in Table 2. b:
Livelli tad- doża ta ’ TMZ huma elenkati f’ Tabella 2.
Adult and paediatric patients 3 years of age or older with recurrent or progressive malignant glioma:
Pazjenti adulti u pedjatriċi minn 3 snin ‘ l fuq bi glijoma malinna rikurrenti jew progressiva:
In patients previously untreated with chemotherapy, TMZ is administered orally at a dose of 200 mg/m2 once daily for the first 5 days followed by a 23 day treatment interruption (total of 28 days).
F’ pazjenti li qabel ma kinux ikkurati bil- kimoterapija, TMZ jittieħed mill- ħalq f’ doża ta ’ 200 mg/ m2 darba kuljum għall- ewwel 5 tijiem, segwiti minn 23 jum ta ’ waqfien mil- kura (total ta ’ 28 jum).
Hypersensitivity to the active substanceor to any of the excipients.
19 Sensittività eċċessiva għas- sustanza attiva jew għal xi sustanzi mhux attivi.
19 Severe myelosuppression (see section 4.4).
Majelosoppressjoni severa (ara sezzjoni 4. 4).
There may be a higher occurrence of PCP when TMZ is administered during a longer dosing regimen.
Jista ’ jkun hemm aktar każijiet ta’ PCP meta TMZ jingħata għal kors itwal.
20 Male patients
20 Pazjenti anzjani jidhru li huma f' riskju akbar li jkollhom newtropenja u tromboċitopenja, meta mqabbla ma ’ pazjenti iżgħar.
4.5 Inter action with other medicinal products and other forms of interaction
4. 5 Prodotti mediċinali oħra li ma jaqblux ma ’ dan il- prodott u affarjiet oħra li jistgħu jibdlu l- effett farmaċewtiku tal- prodott
In a separate phase I study, administration of TMZ with ranitidine did not result in alterations in the extent of absorption of temozolomide or the exposure to its active metabolite monomethyl triazenoimidazole carboxamide (MTIC).
Fi studju separat ta ’ fażi I, l- għotja ta ’ TMZ ma ’ ranitidine ma bidilx il- grad ta ’ assorbiment ta ’ temozolomide jew l- esponiment għal metabolu attiv tiegħu monomethyl triazenoimidazole carboxamide (MTIC).
It is not known whether TMZ is excreted in human milk; thus, breast-feeding should be discontinued while receiving treatment with TMZ.
21 Mhux magħruf jekk TMZ joħroġx mal- ħalib tal- mara; għalhekk, it- treddigħ għandu jitwaqqaf waqt il - kura b’ TMZ.
21 4.7 Effects on ability to drive and use machines
4. 7 Effetti fuq il- ħila biex issuq u tħaddem magni
In patients treated with TMZ, whether used in combination with RT or as monotherapy following RT for newly-diagnosed glioblastoma multiforme, or as monotherapy in patients with recurrent or progressive glioma, the reported very common adverse reactions were similar: nausea, vomiting, constipation, anorexia, headache and fatigue.
F’ pazjenti ikkurati b’ TMZ, kemm kombinat ma ’ RT, jew bħala monoterapija wara RT għal glioblastoma multiforme li tkun għada kif ġiet dijanjostikata, jew bħala monoterapija f’ pazjenti b’ glijoma rikurrenti jew progressiva, l- effetti avversi komuni ħafna rappurtati kienu simili: tqallih, rimettar, stitikezza, anoressija, uġigħ ta ’ ras u għejja.
Convulsions were reported very commonly in the newly- diagnosed glioblastoma multiforme patients receiving monotherapy, and rash was reported very commonly in newly-diagnosed glioblastoma multiforme patients receiving TMZ concurrent with RT and also as monotherapy, and commonly in recurrent glioma.
Aċċessjonijiet kienu rappurtati komuni ħafna f’ pazjenti b’ glioblastoma multiforme li tkun għada kif ġiet dijanjostikata li kienu qed jirċievu monoterapija, u raxx kien rappurtat komuni ħafna f’ pazjenti b’ glioblastoma multiforme li tjun għada kif ġiet dijanjostikata li kienu qed jirċievu TMZ flimkien ma ’ RT kif ukoll bħala monoterapija u komuni b’ glijoma rikurrenti.
Uncommon:
22 Mhux komuni:
22 Psychiatric disorders Common:
Komuni:
Headache Convulsions, consciousness decreased, somnolence, aphasia, balance impaired, dizziness, confusion, memory impairment, concentration impaired, neuropathy, paresthesia, speech disorder, tremor
Uġigħ ta ’ ras Konvulzjonijiet, tnaqqis tal- konxjetà, ngħas, afażja, telf ta ’ l- ekwilibriju, sturdament, konfużjoni, telf tal- memorja, telf tal- konċentrazzjoni, newropatija, parasteżija, ma jitkellmux tajjeb, tregħid
Convulsions, headache Hemiparesis, aphasia, balance impaired, somnolence, confusion, dizziness, memory impairment, concentration impaired, dysphasia, neurological disorder (NOS), neuropathy, peripheral neuropathy, paresthesia, speech disorder, tremor
Konvulżjonijiet, uġigħ ta ’ ras Emipareżi, afażia, telf ta ’ l - ekwilibriju, ngħas, konfużjoni, sturdament, telf tal- memorja, telf tal - konċentrazzjoni, disfażja, disturbi newroloġiċi (NOS), newropatija, newropatija periferali, parasteżija, ma jitkellmux tajjeb, tregħid
Common:
23 Komuni:
23 Common:
Komuni:
Abdominal distension, fecal incontinence, gastrointestinal disorder (NOS), gastroenteritis, haemorrhoids
Nefħa addominali, inkontinenza ta ’ l - ippurgar, disturbi gastro- intestinali (NOS), gastroenterite, emorrojdi
Skin and subcutaneous tissue disorders Very common:
Komuni ħafna:
Uncommon:
24 Mhux komuni:
When laboratory abnormalities and adverse events were combined across concomitant and monotherapy treatment phases, Grade 3 or Grade 4 neutrophil
Meta anormalitajiet tal- laboratorju u effetti avversi kienu kumbinati bejn il- fażijiet b’ kura meta ingħataw flimkien u b’ dik meta ingħata waħdedha, anormalitajiet tan- newtrofili ta ’ Grad 3 jew Grad 4, inklużi effetti newtropeniċi dehru f’ 8% tal - pazjenti.
In clinical trials, the most frequently occurring treatment-related undesirable effects were gastrointestinal disorders, specifically nausea (43%) and vomiting (36%).
Fi provi kliniċi, l- aktar effetti mhux mixtieqa relatati mal- kura li seħħew ta ’ spiss kienu disturbi gastro- intestinali, speċifikament tqallih (43%) u rimettar (36%).
These reactions were usually Grade 1 or 2 (0 – 5 episodes of vomiting in 24 hours) and were either self-limiting or readily controlled with standard anti-emetic therapy.
Dawn ir- reazzjonijet kienu normalment Grad 1 jew 2 (0 – 5 episodji ta ’ rimettar f’ 24 siegħa) u jew waqfu waħidhom jew kienu kontrollati b’ terapija kontra t- tqallih standard.
25 Gender
Sess
In a 400 subject recurrent glioma data set, Grade 4 neutropenia occurred in 8% of female vs 4% of male subjects and Grade 4 thrombocytopenia in 8% of female vs 3% of male subjects in the first cycle of therapy.
F’ set ta ’ dejta għal glijoma b’ 400 individwu, newtropenja ta ’ Grad 4 seħħet fi 8% tan- nisa vs 4% ta ’ l- irġiel u tromboċitopenja ta ’ Grad 4 fi 8% tan- nisa vs 3% ta ’ l- irġiel fl- ewwel ċiklu tat- terapija.
In the event of an overdose, haematological evaluation is needed.
26 infezzjoni, f’ xi każijiet li kienu serji u fit- tul u li wasslu għall- mewt.
26 TMZ was administered as salvage therapy in the follow-up phase in 161 patients of the 282 (57%) in the RT alone arm, and 62 patients of the 277 (22%) in the TMZ + RT arm.
TMZ kien mogħti bħala terapija tas- salvataġġ fil- fażi ta ’ follow- up f’ 161 pazjent mill- 282 (57%) fil - fergħa b’ RT waħdu, u f’ 62 pazjent mill- 277 (22%) fil- fergħa ta ’ TMZ + RT.
The hazard ratio (HR) for overall survival was 1.59 (95% CI for HR=1.33 -1.91) with a log-rank p < 0.0001 in favour of the TMZ arm.
Il- proporzjon tal- periklu (HR) għas- sopravivenza ġenerali kienet ta ’ 1. 59 (95% CI għal HR=1. 33 - 1. 91) b’ log rank p < 0. 0001 favur il- fergħa ta ’ TMZ.