qanastek/EMEA-V3 huggingface dataset:
In combination with capecitabine • For capecitabine dose modifications, see capecitabine summary of product characteristics. • For patients developing the first appearance of a Grade 2 toxicity, which persists at the time of the next docetaxel/ capecitabine treatment, delay treatment until resolved to Grade 0-1, and resume at 100% of the original dose. • For patients developing the second appearance of a Grade 2 toxicity, or the first appearance of a Grade 3 toxicity, at any time during the treatment cycle, delay treatment until resolved to Grade 0-1, then resume treatment with docetaxel 55 mg/ m². • For any subsequent appearances of toxicities, or any Grade 4 toxicities, discontinue the docetaxel dose.
Meta jintuża flimkien ma ’ capecitabine: • Għat- tibdil fid- doża ta ’ capecitabine, ara sommarju tal- karatteristiċi tal- prodott ta ’ capecitabine. • Għal dawk il- pazjenti li titfaċċalhom l- ewwel darba t- tossiċità ta ’ Grad 2, li tippersisti saż- żmien meta jerġa ’ jkun imiss it- trattament b ’ docetaxel / capecitabine, ittardja l- kura sakemm it- tossiċità tinżel għal Grad 0 sa 1, u mbagħad, erġa ’ ibda b’ 100% tad- doża oriġinali. • Għal dawk il- pazjenti li titfaċċalhom għat- tieni darba t- tossiċità ta ’ Grad 2, jew it- tossiċità ta ’ Grad 3 għall- ewwel darba, f’ kwalunkwe ħin waqt iċ- ċiklu tat- trattament, ittardja it- trattament sakemm it- tossiċità tinżel għal Grad 0 sa 1, u mbagħad kompli t- trattament b ’ docetaxel 55 mg/ m2. • Għal kull grad ta ’ tossiċità li titfaċċa sussegwentement, jew għal- kwalunkwe tossiċità ta ’ Grad 4, waqqaf id- doża ta ’ docetaxel.
In combination with cisplatin and 5-fluorouracil If an episode of febrile neutropenia, prolonged neutropenia or neutropenic infection occurs despite G-CSF use, the docetaxel dose should be reduced from 75 to 60 mg/ m2.
Jekk tinqala ’ episodju ta ’ newtropenija bid- deni, newtropenija fit- tul jew newtropenija assoċjata ma ’ infezzjoni, minkejja l- użu ta ’ G- CSF, id- doża ta ’ docetaxel trid titnaqqas minn 75 ghal 60 mg/ m2.
Recommended dose modifications for toxicities in patients treated with docetaxel in combination with cisplatin and 5-fluorouracil (5-FU):
Il- modifikazzjonijiet tad- dożi li huma irrakkomandati f’ pazjenti b’ tossiċita ittrattati b ’ docetaxel meta jintuża flimkien ma ’ cisplatin u 5- fluorouracil (5- FU):
Toxicity
41
Second episode: then reduce docetaxel dose by 20%.
It- tieni episodju: imbagħad naqqas id- doża ta ’ Docetaxel Winthrop b’ 20%.
Second episode: discontinue treatment.
Stomatite/ mukożite L- ewwel episodju: naqqas id- doża ta ’ 5- FU b’ 20%.
Stomatitis/ mucositis grade 3
ta ’ grad 3
First episode: reduce 5-FU dose by 20%.
It- tieni episodju: waqqaf 5- FU biss, fil- korsijiet kollha sussegwenti It- tielet episodju: naqqas id- doża ta ’ docetaxel b’ 20%.
Third episode: reduce docetaxel dose by 20%.
Stomatite/ mukożite L- ewwel episodju: waqqaf 5- FU biss, fil- korsijiet kollha
Stomatitis/ mucositis grade 4
ta ’ grad 4
Second episode: reduce docetaxel dose by 20%.
sussegwenti It- tieni episodju: naqqas id- doża ta ’ docetaxel b’ 20%.
41 Special populations
Pazjenti speċjali:
4.3 Contraindications
4. 4 Kontra- indikazzjonijiet
Docetaxel must not be used in patients with severe liver impairment since there is no data available (see sections 4.2 and 4.4).
Docetaxel ma jistax jintuża f’ pazjenti b’ indeboliment serju tal- fwied għaliex m’ hemmx data dwar dan (ara sezzjonijiet 4. 2 u 4. 4).
Contraindications for other medicinal products also apply, when combined with docetaxel.
42 Il- kontra- indikazzjonijet għall- prodotti mediċinali oħra japplikaw ukoll, meta jkunu użati flimkien ma ’ docetaxel.
42 In patients treated with docetaxel in combination with cisplatin and 5-fluorouracil (TCF), febrile neutropenia and neutropenic infection occurred at lower rates when patients received prophylactic G-CSF.
F’ pazjenti ittrattati b’ docetaxel flimkien ma ’ cisplatin u 5- fluorouracil (TCF), in- newtropenija bid- deni jew in- newtropenija assoċjata ma ’ infezzjoni ġraw f’ rati aktar baxxi f’ pazjenti li ngħataw il- profilassi bil- G- CSF.
Fluid retention
Iż- żamm ta ’ fluwidu
Patients with liver impairment
43 Pazjenti b’ indeboliment tal- fwied
43 Cardiac toxicity
Tossiċità kardijaka
Gastrointestinal reactions Symptoms such as early abdominal pain and tenderness, fever, diarrhea, with or without neutropenia, may be early manifestations of serious gastrointestinal toxicity and should be evaluated and treated promptly.
Reazzjonijiet gastro- intestinali Sintomi bħal uġigħ addominali bikri u sensibilità, deni, dijarea, bin- newtropenija u mingħajrha, jistgħu jkunu l- ewwel sinjali ta ’ tossiċità serja gastro- intestinali u għandhom ikunu evalwati u ittrattati fil - pront.
Leukemia In the docetaxel, doxorubicin and cyclophosphamide (TAC) treated patients, the risk of delayed myelodysplasia or myeloid leukemia requires haematological follow-up.
44 Lewkimja Fil- pazjenti ittrattati b’ docetaxel, doxorubicin u cyclophosphamide (TAC), ir- riskju li jiżviluppaw myelodysplasia jew lewkimija tat- tip myeloid, fit- tard, jirrikjedi l- immoniterjar ematoloġiku wara t - trattament.
Elderly There are no data available in patients > 70 years of age on docetaxel use in combination with doxorubicin and cyclophosphamide.
Anzjani M’ hemmx data disponibbli f’ pazjenti li ghandhom > 70 sena u li kienu fuq docetaxelflimkien ma ’ doxorubicin u cyclophosphamide.
In patients treated with docetaxel every three weeks, the incidence of related nail changes occurred at a rate ≥ 10% higher in patients who were 65 years of age or greater compared to younger patients.
F’ pazjenti ittrattati b’ docetaxel kull tliet ġimgħat, ir- rata relatata ma ’ kambjamenti fid- dwiefer kienet ≥ 10% ogħla f’ pazjenti li kellhom 65 sena jew aktar meta mqabbel ma ’ dawk iżgħar minn 65 sena.
The incidence of the following adverse events (all grades): lethargy, stomatitis, neutropenic infection occurred at rates ≥ 10% higher in patients who were 65 years of age or older compared to younger patients.
L- inċidenza tal- ġrajjiet avversi li jmissu (fil- gradi kollha): telqa, stomatite u infezzjonijiet assoċjati man- newtropenija, graw f’ rati ta ’ ≥10% ogħla f’ pazjenti li kellhom 65 sena jew aktar, meta mqabbla ma ’ pazjenti iżgħar.
44 4.5 Interaction with other medicinal products and other forms of interaction
4. 5 Prodotti mediċinali oħra li ma jaqblux ma ’ dan il- prodott u affarijiet oħra li jistgħu jibdlu l- effett farmaċewtiku tal- prodott
As a result, caution should be exercised when treating patients with these medicinal products as concomitant therapy since there is a potential for a significant interaction.
B’ riżultat ta ’ dan, għandha tkun eżerċitata l- kawtela waqt it - trattament ta ’ pazjenti b’ dawn il- prodotti mediċinali meta jingħataw ma ’ docetaxel, imħabba l - potenzjal li hemm interazzjoni sinifikanti.
In addition, dexamethasone did not affect protein binding of docetaxel.
Għalkemm il- possibbiltà t’ interazzjoni in vivo ta ’ docetaxel ma ’ mediċini oħra li ngħatat konkomittantement ma kienux investigati formalment, l- interazzjonijiet in- vitro b’ sustanzi li huma marbuta sew mal- proteina bħal erythromycin, diphenhydramine, propranolol, propafenone, phenytoin, salicylate, sulfamethoxazole, u sodium valproate, m’ effetwawx ir- rabta ta ’ docetaxel mal- proteina; hekk ukoll dexamethasone m’ effetwawx l - effetti fuq ir- rabta ta ’ Docetexal mal- proteina.
Docetaxel pharmacokinetics in the presence of prednisone was studied in patients with metastatic prostate cancer.
Il- komportament farmakokinetinu ta ’ Docetaxel fil- preżenza ta ’ prednisone kien studjat f’ pazjenti b’ kanċer metastatiku tal- prostata.
Docetaxel should be administered with caution in patients concomitantly receiving potent CYP3A4 inhibitors (e. g. protease inhibitors like ritonavir, azole antifungals like ketoconazole or itraconazole).
Docetexal għandu jingħata b’ kawtela f’ pazjenti li fl- istess ħin qegħdin jirċievu inibituri qawwijin ta ’ CYP3A4 (eż inibituri ta ’ protease bħal ritonavir, mediċini antifungali tat- tip azole bħal ketoconazole jew itraconazole). Studju ta ’ interazzjoni bejn il- mediċini magħmul f’ pazjenti li qegħdin jirċievu
A drug interaction study performed in patients receiving ketoconazole and docetaxel showed that the clearance of docetaxel was reduced by half by ketoconazole, probably because the metabolism of docetaxel involves CYP3A4 as a major (single) metabolic pathway.
45 ketoconazole u docetaxel wera li t- tneħħija ta ’ docetaxel tnaqqas bin- nofs minħabba ketoconazole u dan probabbilment għaliex il- metaboliżmu ta ’ docetaxel jinvolvi lil CYP3A4 bħala l- mezz ewlieni (waħdieni) ta ’ metaboliżmu.
The adverse reactions considered to be possibly or probably related to the administration of docetaxel have been obtained in: • 1312 and 121 patients who received 100 mg/ m² and 75 mg/ m² of docetaxel as a single agent respectively. • 258 patients who received docetaxel in combination with doxorubicin. • 406 patients who received docetaxel in combination with cisplatin.
Ir- reazzjonijiet avversi li jitqiesu possibbilment jew probabilment relatati mat- teħid ta ’ docetaxel inġabru minn:
45 • 92 patients treated with docetaxel in combination with trastuzumab. • 255 patients who received docetaxel in combination with capecitabine. • 332 patients who received docetaxel in combination with prednisone or prednisolone (clinically important treatment related adverse events are presented). • 744 patients who received docetaxel in combination with doxorubicin and cyclophosphamide (clinically important treatment related adverse events are presented). • 300 gastric adenocarcinoma patients (221 patients in the phase III part of the study and 79 patients in the phase II part) who received docetaxel in combination with cisplatin and 5-fluorouracil (clinically important treatment related adverse events are presented). • 174 and 251 head and neck cancer patients who received docetaxel in combination with cisplatin and 5-fluorouracil (clinically important treatment related adverse events are presented).
1312 u 121 pazjent li ħadu 100 mg/ m2 u 75 mg/ m2 ta’ docetaxel bħala sustanza waħedha, • rispettivament. • 258 pazjent li ħadu docetaxel flimkien ma ’ doxorubicin. • 406 pazjent li ħadu docetaxel flimkien ma ’ cisplatin. • 92 pazjent ittrattati b’ docetaxel flimkien ma ’ trastuzumab. • 255 pazjent li ħadu docetaxel flimkien ma ’ capecitabine. • 332 pazjent li ħadu docetaxel flimkien ma ’ prednisone jew prednisolone (effetti avversi klinikament importanti relatati mat- trattament huma irrapportati). • 744 pazjent li ħadu Docetaxel Winthrop flimkien ma ’ doxorubicin u cyclophosphamide (effetti avversi klinikament importanti relatati mat- trattament huma irrapportati). • 300 pazjent b’ adenokarċinoma ta ’ l- istonku (221 pazjent fil- fażi III ta ’ l- istudju u 79 pazjent fil - fażi II), li ħadu docetaxel flimkien ma ’ cisplatin u 5- fluorouracil (effetti avversi klinikament importanti relatati mat- trattament huma irrapportati). • 174 u 251 pazjent b’ kanċer tar- ras u ta ’ l- għonq li ħadu docetaxel flimkien ma’ cisplatin u 5 - fluorouracil (effetti avversi klinikament importanti relatati mat- trattament huma irrapportati).
These reactions were described using the NCI Common Toxicity Criteria (grade 3 = G3; grade 3-4 = G3/ 4; grade 4 = G4) and the COSTART terms.
Dawn ir- reazzjonijiet kienu deskritti bl- użu ta ’ NCI Kriterji ta ’ Tossiċità Komuni (grad 3 = G3; grad 3- 4 = G3/ 4; grad 4 = G4) u t- terminoloġija COSTART.
Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.
F’ kull sezzjoni ta ’ frekwenza, l- effetti mhux mixtieqa huma mniżżla skond is- serjeta tagħhom, bl- aktar serji għandhom jitniżżlu l- ewwel.
The most commonly reported adverse reactions of docetaxel alone are: neutropenia (which was reversible and not cumulative; the median day to nadir was 7 days and the median duration of severe neutropenia (< 500 cells/ mm3) was 7 days), anemia, alopecia, nausea, vomiting, stomatitis, diarrhea and asthenia.
Ir- reazzjonijiet avversi l- aktar komunement irrapportati ta ’ docetaxel innifsu huma: newtropenija (li kienet riversibbli u mhux kumulattiva: il- jum medjan biex jintlaħaq in- nadir kien ta ’ 7 ijiem u ż- żmien medju ta ’ dewmien tan- newtropenija severa (< 500 ċelluli/ mm3) kien ta ’ 7 ijiem), anemija, alopeċja, tqalligħ, rimettar, stomatite, dijarea u astenja.
For combination with capecitabine, the most frequent treatment-related undesirable effects (≥ 5%) reported in a phase III trial in breast cancer patients failing anthracycline treatment are presented (see capecitabine summary of product characteristics).
46 Meta jintuża flimkien ma ’ capecitabine, l- effetti mhux mixtieqa l- aktar komuni assoċjati mat - trattament (≥ 5%) rapportati fil- fażi III ta ’ l- istudji fil- pazjenti li kellhom kanċer tas- sider, meta l- kura b’ anthracycline falliet, qed jingħataw (ara s- sommarju tal- karatteristiċi tal- prodott ta ’ capecitabine).
46 extremities and may become generalised with a weight gain of 3 kg or more.
In- nefħa periferika x’ aktarx tibda fl- estremitajiet t’ isfel u tista ’ issir ġeneraliżżata b’ żieda fil- piż ta ’ 3 kg jew aktar.
Docetaxel Winthrop 100 mg/ m² single agent
Docetaxel Winthrop 100 mg/ m2 bħala sustanza użata waħedha:
MedDRA System Organ classes Investigations
Sistema tal- Klassifika tal - Organi fid - Database MedDRA
Very common adverse Common adverse reactions reactions ≥ 10% of patients ≥ 1 to < 10% of patients G3/ 4 Blood bilirubin increased (< 5%); G3/ 4 Blood alkaline phosphatase increased (< 4%); G3/ 4 AST increased (< 3%); G3/ 4 ALT increased (< 2%)
Reazzjonijiet Avversi komuni ħafna ≥ 10% tal- pazjenti
Uncommon adverse reactions ≥ 0.1 to < 1% of patients
Reazzjonijiet Avversi komuni > 1 sa < 10% tal - pazjenti
Cardiac failure
Insuffiċjenza tal - qalb
Blood and lymphatic system disorders
47 Sistema tal- Klassifika tal - Organi fid - Database MedDRA
Neutropenia (G4:
Reazzjonijiet Avversi komuni > 1 sa < 10% tal - pazjenti Tromboċitopenija (G4:
Thrombocytopenia (G4:
Disturbi tad- demm u tas - Newtropenija (G4:
Peripheral sensory neuropathy (G3:
Newropatija periferika tas- sensazzjoni (G3:
4.1%); Peripheral motor neuropathy (G3/ 4:
4. 1%); Newropatija periferika tal- movimenti (G3/ 4:
Dyspnoea (severe:
Dispneja (sever:
Constipation (severe:
5. 3%);
5.3%); 0.2%); Diarrhoea (G3/ 4:
Stitikezza (severa:
4%); Abdominal pain Nausea (G3/ 4:
0. 4%)
4%); (severe:
Dijarea (G3/ 4:
1%); Vomiting (G3/ 4:
4%); Rimettar (G3/ 4:
Oesophagitis (severe:
0. 2%); Uġigħ ta ’ żaqq (sever:
0.4%)
0. 3%)
1.4%) Arthralgia
Majalġja (severa 1. 4%)
Anorexia
Artralġja
Infections and infestations
Disturbi fil- metaboliżmu Anoreksja u n- nutrizzjoni Infezzjonijiet u infestazzjonijiet Disturbi vaskulari
5.7%; Infection associated including sepsis and with G4 neutropenia pneumonia, fatal in (G3/ 4:
4. 6%) Pressjoni baxxa; Pressjoni għolja; Emoraġija Reazzjoni fis- sit ta ’ l -
4.6%) 1.7%)
Disturbi ġenerali u
Vascular disorders
Żamm tal- fluwidu (sever:
Hypotension; Hypertension; Haemorrhage
infuzjoni;
General disorders and administration site conditions
kondizzjonijiet ta ’ mnejn 6. 5%) Uġigħ fis- sider, mhux jingħata
Fluid retention (severe:
Astenja (severa:
Infusion site reaction; 6.5%); Non-cardiac chest pain Asthenia (severe:
11. 2%); Uġigħ
(severe:
dak tal- qalb (sever:
0.4%) 11.2%); Pain
0. 4%)
48 Docetaxel Winthrop 75 mg/ m² single agent
Docetaxel Winthrop 75 mg/ m² bħala sustanza użata waħedha:
MedDRA System Organ classes
Sistema tal- Klassifika tal -- Organi fid- Database MedDRA
Common adverse reactions ≥ 1 to < 10% of patients
Reazzjonijiet Avversi komuni > 1 sa < 10% tal- pazjenti
G3/ 4 Blood bilirubin increased (< 2%)
G3/ 4 Żieda fil- bilirubin fid - demm (< 2%)
2.5%)
2. 5%) Stitikezza
0.8%); Diarrhea (G3/ 4:
0. 8%); Dijarea (G3/ 4:
Constipation
Alopeċja;
Skin and subcutaneous tissue disorders Musculoskeletal and connective tissue disorders
taħt il- ġilda
Alopecia; Skin reaction (G3/ 4:
Reazzjonijiet tal- ġilda (G3/ 4:
Nail disorders (severe:
Disturbi muskolu- skeletrali u tal - connective tissue
Infections and infestations Vascular disorders General disorders and administration site conditions
Infezzjonijiet u infestazzjonijiet Disturbi vaskulari Disturbi ġenerali u kondizzjonijiet ta ’ mnejn jingħata
12.4%); Fluid retention (severe:
5%) Astenja (severa 12. 4%); Żamm tal- fluwidu (sever:
0.8%); Pain
0. 8%) Uġigħ
Hypotension
Pressjoni baxxa
49 Docetaxel Winthrop 75 mg/ m² in combination with doxorubicin
49 Docetaxel Winthrop 75 mg/ m² użat flimkien ma ’ doxorubicin:
Very common adverse Common adverse reactions reactions ≥ 10% of patients ≥ 1 to < 10% of patients
Reazzjonijiet Avversi komuni > 1 to < 10% tal - pazjenti
Gastrointestinal disorders
7. 8%); Dijarrea (G3/ 4:
Musculoskeletal and connective tissue disorders
Disturbi muskolu - skeletrali u tal- connective tissue u ta ’ l- għadam
Infusion site reaction 8.1%); Fluid retention (severe:
Żamm tal- fluwidu (sever:
1.2%); Pain
1. 2%); Uġigħ
50 Docetaxel Winthrop 75 mg/ m² in combination with cisplatin
50 Docetaxel Winthrop 75 mg/ m² użat flimkien ma ’ cisplatin:
Common adverse reactions ≥ 1 to < 10% of patients
Reazzjonijiet Avversi komuni > 1 to < 10% tal - pazjenti
Uncommon adverse reactions ≥ 0.1 to < 1% of patients
Effetti mhux miztieqa mhux komuni > 0. 1 to < 1% tal - pazjenti
G3/ 4 AST increased (0.5%); G3/ 4 Blood alkaline phosphatase increased (0.3%)
G3/ 4 Żieda fl- AST (0. 5%); G3/ 4 Żieda fl - alkaline phosphatase fid- demm (0. 3%)
0.7%)
0. 7%) Insuffiċjenza tal- qalb Newtropenija bid- deni
0.5%) Nervous system disorders
Disturbi fis- sistema nervuża
3.7%); Peripheral motor neuropathy (G3/ 4:
3. 7%); Newropatija periferika tal- movimenti (G3/ 4:
Gastrointestinal disorders
Stitikezza Disturbi gastro- intestinali
0.7%); Skin reaction (G3/ 4:
0. 7%); Reazzjoni tal - ġilda (G3/ 4:
0.5%)
0. 5%)
Infections and infestations
Disturbi fil- metaboliżmu u Anoreksja n- nutrizzjoni Infezzjonijiet u infestazzjonijiet
Infusion site reaction; Pain
Uġigħ
conditions
jingħata
Fluid retention (severe:
(sever:
51 Docetaxel Winthrop 100 mg/ m² in combination with trastuzumab
Docetaxel Winthrop 100 mg/ m² użat flimkien ma ’ trastuzumab:
Common adverse reactions ≥ 1 to < 10% of patients
Reazzjonijiet Avversi komuni hafna ≥ 10% tal- pazjenti
Investigations Cardiac disorders Blood and lymphatic system disorders
Disturbi tad- demm u tas - sistema limfatika
Weight increased Neutropenia (G3/ 4:
Newtropenija (G3/ 4:
32%); Febrile neutropenia (includes neutropenia associated with fever and antibiotic use) or neutropenic sepsis
32%); Newtropenija bid- deni (tinkludi n - newtropenija assoċjata mad- deni u l- użu ta ’ l- antibijotiċi) jew newtropenija bis- sepsis
Paresthesia; Headache; Dysgeusia; Hypoaesthesia
Parasteżija; Ugigħ ta ’ ras; Disgewżja; Ipoestesija
Respiratory, thoracic and mediastinal disorders
Disturbi fl- għajnejn Disturbi respiratorji, toraċiċi u medjastinali
Epistaxis; Pharyngolaryngeal pain; Nasopharyngitis; Dyspnoea; Cough; Rhinorrhoea
Tidmigħ miżjud; Konġuntivite Fġir l- imnieħer; Uġigħ fil- farinġi u l- larinġi; Farinġite tal- parti nażali; Qtugħ ta ’ nifs; Sogħla; Tnixxija mill- imnieħer
Nausea; Diarrhoea; Vomiting; Constipation; Stomatitis; Dyspepsia; Abdominal pain
Tqalligħ; Dijarea; Rimettar; Stitikezza; Stomatite; Dispepsja; Ugigħ addominali
Skin and subcutaneous tissue disorders Musculoskeletal and connective tissue disorders Metabolism and nutrition disorders
Disturbi fil- ġilda u fit- tessuti ta ’ taħt il- ġilda Disturbi muskolu- skeletrali u tal- connective tissue u ta ’ l - għadam Disturbi fil- metaboliżmu u n - nutrizzjoni
Alopecia; Erythema; Rash; Nail disorders Myalgia; Arthralgia; Pain in extremity; Bone pain; Back pain Anorexia
Alopeċja; Eritema; Raxx; Mard tad- dwiefer Majalġja; Artralġja; Uġigħ fl - estremitajiet; Uġigħ fl- għadam; Uġigħ tad- dahar Anoreksja
Lymphoedema
Letarġija
Asthenia; Oedema peripheral; Pyrexia; Fatigue; Mucosal inflammation; Pain; Influenza like illness; Chest pain; Chills
Astenja; Edima periferika; Deni; Għejja; Infjammazzjoni tal - mukoża; Uġigħ; Mard bħall - influwenza; Uġigħ fis- sider; Riħ bid- deni
Insomnia
Insonnja
52 Docetaxel Winthrop 75 mg/ m² in combination with capecitabine
Docetaxel Winthrop 75 mg/ m² użat flimkien ma ’ capecitabine:
MedDRA System Organ classes
Sistema tal- Klassifika tal- Organi fid- Database MedDRA Investigazzjonijiet
Very common adverse reactions ≥ 10% of patients
Reazzjonijiet Avversi komuni ħafna ≥ 10% tal- pazjenti 52
Common adverse reactions ≥ 1 to < 10% of patients
Reazzjonijiet Avversi komuni ħafna ≥ 10% tal- pazjenti
Weight decreased; G3/ 4 Blood bilirubin increased (9%)
Reazzjonijiet Avversi komuni > 1 to < 10% tal- pazjenti
Pharyngolaryngeal pain (G3/ 4:
Uġigħ fil- farinġi u l- larinġi (G3/ 4:
1%); Cough (G3/ 4: < 1%); Epistaxis (G3/ 4: < 1%)
1%); Sogħla (G3/ 4: < 1%); Fġir l- imnieħer (G3/ 4: < 1%) Uġigh fil- parti ta ’ fuq taż -
18%); Diarrhoea (G3/ 4:
18%); Dijarea (G3/ 4:
Abdominal pain upper; Dry mouth
żaqq; Ħalq xott Dermatite;
Skin and subcutaneous tissue disorders
Disturbi fil- ġilda u fit- tessuti ta ’ taħt
Musculoskeletal and connective tissue disorders Metabolism and nutrition disorders Infections and infestations
Disturbi muskolu- skeletrali u tal - connective tissue
53 Docetaxel Winthrop 75 mg/ m² in combination with prednisone or prednisolone
Docetaxel Winthrop 75 mg/ m² użat flimkien ma ’ prednisone jew prednisolone:
Blood and lymphatic system disorders
Disturbi tad- demm u tas- sistema limfatika Disturbi fis- sistema nervuża
4.9%)
32%); Tromboċitopenija (G3/ 4:
Thrombocytopenia (G3/ 4:
0. 6%); Anemija (G3/ 4:
Peripheral sensory neuropathy (G3/ 4:
4. 9%) Newtropenija bid- deni Newropatija periferika tas - Newropatija periferika tal - sensazzjoni (G3/ 4:
0%)
1. 2%); movimenti (G3/ 4:
Peripheral motor neuropathy (G3/ 4:
0%) Disgewżja (G3/ 4:
2.4%); Diarrhoea (G3/ 4:
2. 4%); Dijarea (G3/ 4:
Skin and subcutaneous tissue disorders Musculoskeletal and connective bone disorders Metabolism and nutrition disorders
Disturbi fil- ġilda u fit- tessuti ta ’ taħt il- ġilda
Alopecia; Nail disorders (no severe) Anorexia (G3/ 4:
Alopeċja; Raxx esfoljattiv (G3/ 4:
0.6%)
0. 3%) Mard tad- dwiefer (mhux sever)
Exfoliative rash (G3/ 4:
Artralġja (G3/ 4:
0.3%) Arthralgia (G3/ 4:
0. 3%); Majalġja (G3/ 4:
0.3%); Myalgia (G3/ 4:
Anoreksja (G3/ 4:
0.3%)
0. 6%)
Infections and infestations General disorders and administration site conditions Immune system disorders
Infezzjonijiet u infestazzjonijiet Mard ġenerali u kondizzjonijiet ta ’ mnejn jingħata
3.3%) Fatigue (G3/ 4:
3. 3%) Għejja (G3/ 4:
54 Docetaxel Winthrop 75 mg/ m² in combination with doxorubicin and cyclophosphamide
Docetaxel Winthrop 75 mg/ m² użat flimkien ma ’ doxorubicin u cyclophosphamide:
MedDRA System Organ classes Investigations
Sistema tal- Klassifika tal- Organi fid - Database MedDRA Investigazzjonijiet
Very common adverse Common adverse reactions reactions ≥ 10% of patients ≥ 1 to < 10% of patients Weight increased or decreased (G3/ 4:
Reazzjonijiet Avversi komuni ħafna ≥ 10% tal- pazjenti Żieda jew tnaqqis fil - piż (G3/ 4:
Uncommon adverse reactions ≥ 0.1 to < 1% of patients
Reazzjonijiet Avversi komuni > 1 to < 10% tal - pazjenti
0.1%); Congestive heart failure
Insuffiċjenza konġestiva tal- qalb
2.0%); Febrile neutropenia
2. 0%); Newtropenija bid - deni
Nervous system disorders
Newropatija periferika
0.1%)
Disgewżja (G3/ 4:
Syncope (G3/ 4:
tal- movimenti (G3/ 4:
Lacrimation disorder (G3/ 4:
Mard tad- tidmigħ (G3/ 4:
0.1%); Conjunctivitis (G3/ 4:
0. 1%); Konġuntivite (G3/ 4:
5.1%); Abdominal pain (G3/ 4:
5. 1%); Stomatite (G3/ 4:
Stomatitis (G3/ 4:
4. 3%); Dijarea (G3/ 4:
0.5%) 7.1%); Vomiting (G3/ 4:
3. 2%); Stitikezza (G3/ 4:
4.3%); Diarrhoea (G3/ 4:
0. 4%)
3.2%); Constipation (G3/ 4:
Ugigħ addominali (G3/ 4:
0.4%)
0. 5%)
Colitis/ enteritis/ large intestine perforation
Kolite/ enterite/ perforament tal- musrana l- kbira
Skin and subcutaneous tissue disorders
54 Sistema tal- Klassifika Reazzjonijiet tal- Organi fid - Avversi komuni Database MedDRA ħafna ≥ 10% tal- pazjenti Disturbi fil- ġilda u fit - Alopeċja; tessuti ta ’ taħt il- ġilda Tossiċità tal- ġilda (G3/ 4:
0.4%)
Ma kienx hemm imwiet bis- sepsis.
Musculoskeletal and connective tissue disorders
Reazzjonijiet Avversi komuni > 1 to < 10% tal - pazjenti
Myalgia (G3/ 4:
Disturbi vaskulari Vasodilatazzjoni (G3/ 4:
0.4%)
0. 9%) Disturbi ġenerali u Astenja (G3/ 4:
Metabolism and nutrition disorders
11%); kondizzjonijiet ta ’ Deni (G3/ 4:
2.2%)
1. 2%); mnejn jingħata Edima periferika (G3/ 4:
Infection (G3/ 4:
0. 4%) Disturbi fis- sistema Sensittività eċċessiva immuni (G3/ 4:
There were no septic deaths.
1. 1%) Disturbi fis- sistema Amenorreja riproduttiva u fis- sider
56 Docetaxel Winthrop 75 mg/ m² in combination with cisplatin and 5-fluorouracil for gastric adenocarcinoma cancer
55 Docetaxel Winthrop 75 mg/ m² użat flimkien ma ’ cisplatin u 5- fluorouracil għal kanċer tat- tip adenokarċinoma ta ’ l- istonku:
Cardiac disorders Blood and lymphatic system disorders
Sistema tal- Klassifika tal- Organi fid- Database MedDRA Disturbi fil- qalb Disturbi tad- demm u tas- sistema limfatika
Anaemia (G3/ 4:
Reazzjonijiet Avversi komuni ħafna ≥ 10% tal- pazjenti Anemija (G3/ 4:
Arrhythmia (G3/ 4:
Reazzjonijiet Avversi komuni > 1 to < 10% tal- pazjenti Arritmija (G3/ 4:
0%)
Tidmigħ miżjud (G3/ 4:
Ear and labyrinth disorders
0%) Nuqqas ta ’ smigħ (G3/ 4:
Hearing impaired (G3/ 4:
0%) Stitikezza (G3/ 4:
Diarrhoea (G3/ 4:
Dijarea (G3/ 4:
1%)
2. 3%); Żamm tal- fluwidu (sever/ li
Immune system disorders
1%) Disturbi fis- sistema immuni
57 Docetaxel Winthrop 75 mg/ m² in combination with cisplatin and 5-fluorouracil for Head and Neck cancer
56 Docetaxel Winthrop 75 mg/ m² użat flimkien ma ’ cisplatin and 5- fluorouracil (għal kanċer tar- ras u ta ’ l- għonq):
• Induction chemotherapy followed by radiotherapy (TAX 323)
• Kimoterapija Induttiva sefgwita bi radjuterapija (TAX323)
MedDRA System Organ classes
Sistema tal- Klassifika tal - Organi fid- Database MedDRA Investigazzjonijiet
Uncommon adverse reactions ≥ 0.1 to < 1% of patients
Reazzjonijiet Avversi mhux komuni > 0. 1 to < 1% tal - pazjenti Arritmija (G3/ 4:
Myocardial ischemia (G3/ 4:1.7%)
Mard iskemiku tal - mijokardju (G3/ 4: 1. 7%)
Anemia (G3/ 4:
76. 3%) Anemija (G3/ 4:
9.2%); Thrombocytopenia (G3/ 4:
9. 2%); Tromboċitopenija (G3/ 4:
5.2%) Nervous system disorders
5. 2%)
0.6%)
Disgewżja / Parosmja Sturdament Disturbi fis- sistema nervuża Newropatija periferika tas- sensazzjoni (G3/ 4: 0. 6%)
Ear and labyrinth disorders
Disturbi fil- widnejn u fis - sistema labirintika
Hearing impaired
Nuqqas ta ’ smigħ
0.6%)
Tqalligħ (G3/ 4: 0. 6%) Stomatite (G3/ 4: 4. 0%) Dijarea (G3/ 4: 2. 9%) Rimettar (G3/ 4: 0. 6%)
0.6%)
Esofaġite/ disfaġja / odinofaġja (G3/ 4: 0. 6%); Uġigħ addominali; Dispepsja; Emoraġija gastrointestinali (G3/ 4: 0. 6%);
0.6%)
Raxx bil- ħakk; Ġilda xotta; Ġilda esfoljattiva (G3/ 4: 0. 6%)
Metabolism and nutrition disorders
Disturbi fil- metaboliżmu u n- nutrizzjoni Infezzjonijiet u infestazzjonijiet
Infections and infestations Neoplasms benign, malignant and unspecified (incl cysts and polyps)
0. 6%) Infezzjoni (G3/ 4: 6. 3%); Infezzjoni bin - newtropenija
6.3%); Neutropenic infection
Neoplażmi beninni, malinni u dawk mhux speċifikati (inklużi ċesti u polipi)
Cancer pain (G3/ 4:
Uġigħ tal- kanċer (G3/ 4:
Vascular disorders
57 Sistema tal- Klassifika tal - Organi fid- Database MedDRA Disturbi vaskulari
Venous disorder (G3/ 4:
Reazzjonijiet Avversi Reazzjonijiet Avversi komuni ħafna komuni ≥ 10% tal- pazjenti > 1 to < 10% tal - pazjenti Mard tal- vini (G3/ 4:
3.4%); Pyrexia (G3/ 4:
Letarġija (G3/ 4: 3. 4%); Deni (G3/ 4:
0.6%); Fluid retention; Oedema
0. 6%); Żamm tal- fluwidu; Edima
58 • Induction chemotherapy followed by chemoradiotherapy (TAX 324)
• Kimoterapija Induttiva segwita bi kimoradjuterapija (TAX324)
Eye disorders Ear and labyrinth disorders
Newropatija periferika
Hearing impaired (G3/ 4:
Newropatija periferika tal- movimenti (G3/ 4: tas- sensazzjoni (G3/ 4:
1.2%)
0. 4%); 1. 2%)
Lacrimation increased
Tidmigħ miżjud;
Gastrointestinal disorders
Disturbi fil- widnejn u fis- sistema labirintika
Nausea (G3/ 4:
Nuqqas ta ’ smigħ (G3/ 4:
13.9%); Stomatitis (G3/ 4:
0. 8%); Disturbi gastro -
20.7%); Vomiting (G3/ 4:
Tqalligħ (G3/ 4:
8.4%); Diarrhea (G3/ 4:
20. 7%); Rimettar (G3/ 4:
Infections and infestations Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Infezzjonijiet u infestazzjonijiet
Neutropenic infection Cancer pain (G3/ 4:
Uġigh tal- kanċer (G3/ 4:
Vascular disorders General disorders and administration site conditions
Disturbi vaskulari Disturbi ġenerali u kondizzjonijiet ta ’ mnejn jingħata
Venous disorder
Disturbi fil- vini
59 Post-marketing experience
L- esperjenza wara Li tpoġġa fis- suq:
These reactions sometimes appear during the infusion of the medicinal product.
Dawn ir- reazzjonijiet tfaċċaw x’ imdaqqiet waqt l- infużjoni tal- prodott mediċinali.
60 Hepatobiliary disorders Very rare cases of hepatitis, sometimes fatal primarily in patients with pre-existing liver disorders, have been reported.
Każijiet rari ħafna ta ’ epatite, kultant fatali speċjalment f’ pazjenti li kellhom mard preċedenti tal - fwied, kienu irrapportati.
Docetaxel was found to be cytotoxic in vitro against various murine and human tumour cell lines and against freshly excised human tumour cells in clonogenic assays.
60 Docetaxel instab li huwa ċitotossiku in vitro għall- linji ċellulari ta ’ tumuri li huma derivati mill - ġrieden u l- bniedem, u kontra ċelluli umani meħudin minn tumuri hekk kif dawn ikunu tneħħew, fi studji klonoġeniċi fil- laboratorju.
Clinical data
Tagħrif kliniku
Docetaxel was administered as a 1-hour infusion, all other medicinal products were given as intravenous bolus on day one.
Iż- żewġ gruppi kienu ngħataw il- kura darba kull 3 ġimgħat għal 6. ċikli Docetaxel kien ingħata bħala infużjoni tul siegħa, waqt li l- prodotti mediċinali l- oħra kienu ngħataw bħala bolus fil- vini fl - ewwel jum.
61 An interim analysis was performed with a median follow up of 55 months.
Sadattant, analiżi nħaddmet fuq perijodu medjan ta ’ 55 xahar.
Incidence of relapses at 5 years was reduced in patients receiving TAC compared to those who received FAC (25% versus 32%, respectively) i. e. an absolute risk reduction by 7% (p = 0.001).
L- inċidenza tar- rikaduta hekk kif għaddew 5 snin tnaqqas fil- pazjenti li rċevew TAC meta mqabbel ma ’ dawk li rċevew FAC (25% kontra 32%, rispettivament) li tfisser riskju assolut imnaqqas b’ 7% (p- 0. 001).
Docetaxel Winthrop as single agent
61 Docetaxel Winthrop meta jintuża waħdu
In alkylating-failure patients, docetaxel was compared to doxorubicin (75 mg/ m² every 3 weeks).
F’ dawk il- pazjenti li kienu ħadu l- kors bis- sustanza alkylating, li falla, docetaxel kien imqabbel ma ’ doxorubicin (75 mg/ m2 kull 3 ġimgħat).
37%, p = 0.01) and shortened time to response (12 weeks vs.
Mingħajr m’ affettwa iż- żmien totali tas- sopravivenza (għal docetaxel 15- il xahar kontragħal doxorubicin 14- il xahar, p = 0. 38), jeww iż- zmien sakemm javvanza t- tumur (b’ docetaxel 27 ġimgħa kontra li d- doxorubicina kien ta ’ 23 ġimgħa, p = 0. 54), docetaxel wera rata ta ’ rispons aktar għolja (52% kontra 37%, p = 0. 01) u qassar iż- żmien għar- rispons (12- il ġimgħa vs 23 ġimgħa, p = 0. 007).
An open-label, multicenter, randomized phase III study was conducted to compare docetaxel monotherapy and paclitaxel in the treatment of advanced breast cancer in patients whose previous therapy should have included an anthracycline.
Studju fil- fażi III, magħmul f’ ċentri multipli, fejn kemm il- pazjenti kif ukoll l- investigaturi kienu jafu x’ mediċini qed jintużaw, u li il- pazjenti tqassmu mingħajr għażla, sar biex il- monoterapija b’ docetaxel titqabbel ma ’ pacilitaxel fit- trattament ta ’ kanċer tas- sider avvanzat, f’ pazjenti li t- terapija preċedenti kellha tinkludi xi anthracycline.
More grade 3/ 4 adverse events were observed for docetaxel monotherapy (55.4%) compared to paclitaxel (23.0%).
Aktar ġrajjiet avversi kienu innotati b’ docetaxel bħala monoterapija (55. 4%) meta mqabbel ma ’ paclitaxel (23%).
62 Docetaxel Winthrop in combination with doxorubicin
Docetaxel Winthrop użat flimkien ma ’ doxorubicin
One large randomized phase III study, involving 429 previously untreated patients with metastatic disease, has been performed with doxorubicin (50 mg/ m²) in combination with docetaxel (75 mg/ m²) (AT arm) versus doxorubicin (60 mg/ m²) in combination with cyclophosphamide (600 mg/ m²) (AC arm).
Dawn ingħataw doxorubicin (50 mg/ m2) flimkien ma ’ docetaxel (75 mg/ m2) (il- fergħa AT) kontradoxorubicin (60 mg/ m2) flimkien ma ’ cyclophosphamide (600 mg/ m2) (il- fergħa AC).
In this trial, AT arm showed a higher incidence of severe neutropenia (90% versus 68.6%), febrile neutropenia (33.3% versus 10%), infection (8% versus 2.4%), diarrhea (7.5% versus 1.4%), asthenia (8.5% versus 2.4%), and pain (2.8% versus 0%) than AC arm.
Minn naħa l- oħra, il- fergħa
On the other hand, AC arm showed a higher incidence of severe anemia (15.8% versus 8.5%) than AT arm, and, in addition, a higher incidence of severe cardiac toxicity: congestive heart failure (3.8% versus 2.8%), absolute LVEF decrease ≥ 20% (13.1% versus 6.1%), absolute LVEF decrease ≥ 30% (6.2% versus 1.1%).
62 AC uriet inċidenza ogħla ta ’ anemija severa (15. 8% kontra 8. 5%) mill- fergħa AT, kif ukoll inċidenza ogħla ta ’ tossiċita severa kardijaka: insuffiċenza konġestiva tal- qalb (3. 8% kontra 2. 8%), ir- rata assoluta tal- LVEF tnaqqset ≥ 20% (13. 1% kontra 6. 1%), ir- rata assoluta tal- LVEF tnaqqset ≥ 30% (6. 2% kontra 1. 1%).
Docetaxel Winthrop in combination with trastuzumab
Docetaxel Winthrop użat flimkien ma ’ trastuzumab
Non-small cell lung cancer
63 Kanċer tal- pulmun li mhux ikkaratterizzat b’ ċelluli żgħar
There was less use of morphinic analgesic (p < 0.01), non-morphinic analgesics (p < 0.01), other disease-related medications (p = 0.06) and radiotherapy (p < 0.01) in patients treated with docetaxel at 75 mg/ m² compared to those with BSC.
Kien hemm inqas użu tal- morfina għall - uġigħ (p < 0. 01), sustanzi ghall- ugigħ mhux tat- tip tal- morfina (p < 0. 01), mediċini oħra relatati mal - marda (p = 0. 06) u r- radjuterapija (p < 0. 01), f’ pazjenti ittrattati b’ docetaxel b’ doża ta ’ 75 mg/ m2, komparat ma dawk fuq l- AKS.
64 Secondary end-points included change of pain, global rating of quality of life by EuroQoL-5D, Lung Cancer Symptom Scale, and changes in Karnosfky performance status.
L- aħħar stadji sekondarji tal- proċess kienu jinkludu bidla fl- uġigħ, ir- rata globali tal- kwalità tal- ħajja bl- użu tal- EuroQoL- 5D, Skala ta ’ Sintomi għall- Kanċer tal- Pulmun, u bidliet fl- istatus tal- wirja ta ’ Karnosfky.
For docetaxel/ carboplatin combination, neither equivalent nor non-inferior efficacy could be proven compared to the reference treatment combination VCis.
Għad- docetaxel/ carboplatin flimkien, l- effikaċja, li kienet la ekwivalenti u anqas ma kienet inferjuri, ma setgħetx tkun ippruvata meta mqabbla mat- trattament ta ’ referenza, iġifieri VCis.
Prostate cancer
64 Kanċer tal- prostata
The safety and efficacy of docetaxel in combination with prednisone or prednisolone in patients with hormone refractory metastatic prostate cancer were evaluated in a randomized multicenter phase III trial.
Is- sigurtà u l- effikaċja ta ’ docetaxel użat flimkien ma ’ prednisone jew prednisolone, f’ pazjenti li qed ibatu minn kanċer metastatiku tal- prostata li mhux sensittiv għall- kura bl- ormoni kienu studjati f’ ċentri multipli, mingħajr għażla tal- pazjenti, fil- prova fażi III.
A total of 1006 patients with KPS ≥ 60 were randomized to the following treatment groups: • Docetaxel 75 mg/ m2 every 3 weeks for 10 cycles. • Docetaxel 30 mg/ m2 administered weekly for the first 5 weeks in a 6 week cycle for 5 cycles. • Mitoxantrone 12 mg/ m2 every 3 weeks for 10 cycles.
Docetaxel 75 mg/ m2 kull 3 ġimgħat għal 10 ċikli. • Docetaxel 30 mg/ m2 li ngħata kull ġimgħa, ghall- ewwel 5 ġimgħat, f’ ċiklitwil ta ’ 6 ġimghat, • mogħti għal 5 ċikli.
65 Gastric adenocarcinoma
65 Adenokarċinoma ta ’ l- istonku
A multicenter, open-label, randomized trial, was conducted to evaluate the safety and efficacy of docetaxel for the treatment of patients with metastatic gastric adenocarcinoma, including adenocarcinoma of the gastroesophageal junction, who had not received prior chemotherapy for metastatic disease.
Studju f’ ċentri multipli fejn kemm l- investigatur kif ukoll il- pazjent kienu jafu x’ mediċini kienu qed jintużaw, u li il- pazjenti tqassmu f’ gruppi mingħajr għażla, sar biex ikunu evalwati s- sigurtà u l - effikaċja ta ’ docetaxel, għat- trattament ta ’ pazjenti li kellhom adenokarċinoma metastatika ta ’ l - istonku, inklużi dawk li kellhom adenokarċinoma fil- parti fejn l- istonku jagħqad ma ’ l- esofagu, u li ma kienux ħadu qabel kimoterapija għall- mard metastatiku.
A total of 445 patients with KPS > 70 were treated with either docetaxel (T) (75 mg/ m2 on day 1) in combination with cisplatin (C) (75 mg/ m2 on day 1) and 5-fluorouracil (F) (750 mg/ m2 per day for 5 days) or cisplatin (100 mg/ m2 on day 1) and 5-fluorouracil (1000 mg/ m2 per day for 5 days).
Total ta ’ 445 pazjent b’ KPS > 70 kienu ittrattati b’ docetaxel (T) (75 mg/ m2 fl- ewwel jum) flimkien ma ’ cisplatin (C) (75 mg/ m2 fl- ewwel jum) u 5- fluorouracil (F) (750 mg/ m2 kuljum għal 5 ijiem), jew cisplatin (100 mg/ m2 fl- ewwel jum) u 5 - fluorouracil (1000 mg/ m2 kuljum għal 5 ijiem).
The median number of cycles administered per patient was 6 (with a range of 1-16) for the TCF arm compared to 4 (with a range of 1-12) for the CF arm.
In- numru medjan ta ’ ċikli li ngħataw lil kull pazjent kien ta ’ 6 (b’ medda ta ’ 1- 16) għall- fergħa TCF, meta mqabbel ma ’ 4 (b’ medda ta ’ 1- 12) għall- fergħa CF.
Time to progression (TTP) was the primary endpoint.
Iż - żmien li ħa t- tumur biex avvanza (TTP) kien l- aħħar stadju primarju tal- proċess.
Head and neck cancer
66 Kanċer tar- ras u ta ’ l- għonq
• Induction chemotherapy followed by radiotherapy (TAX323) The safety and efficacy of docetaxel in the induction treatment of patients with squamous cell carcinoma of the head and neck (SCCHN) was evaluated in a phase III, multicenter, open-label, randomized trial (TAX323).
• Kimoterapija Induttiva sefgwita bi radjuterapija (TAX323) Is- sigurtà u l- effikaċja ta ’ docetaxel fit- trattament induttiv ta ’ pazjenti li kellhom kanċer tat- tip squamous cell tar- ras u l- għonq (SCCHN), kienu evalwati fil fażi III ta ’ studju magħmul minn ċentri multipli, fejn kemm l- investigatur kif ukoll il- pazjent kienu jafu x’ mediċini qed jintużaw, u fejn il - pazjenti tqassmu mingħajr għażla (TAX323).
Patients on the docetaxel arm received docetaxel (T) 75 mg/ m2 followed by cisplatin (P) 75 mg/ m2 followed by
Pazjenti tal- fergħa ta ’ docetaxel, ingħataw docetaxel (T) 75 mg/ m2, segwit minn cisplatin (P) 75 mg/ m2, segwit minn 5- fluorouracil (F) 750 mg/ m2 kuljum bħala infużjoni kontinwa għal 5 ijiem.
This regimen was administered every three weeks for 4 cycles in case at least a minor response (≥ 25% reduction in bidimensionally measured tumour size) was observed after 2 cycles.
Din is- sistema ta ’ kura ingħatat kull tliet ġimgħat għal 4 ċikli fil- każ li, ta ’ l- anqas, rispons ċkejken kien ikun osservat wara żewġ ċikli (≥ 25% tnaqqis fid- daqs tat - tumur permezz ta ’ kejl f’ żewġ dimensjonijiet).
At the end of chemotherapy, with a minimal interval of 4 weeks and a maximal interval of 7 weeks, patients whose disease did not progress received radiotherapy (RT) according to institutional guidelines for 7 weeks (TPF/ RT).
Fit- tmiem tal- kimoterapija, b’ intervall minimu ta ’ 4 ġimgħat u intervall massimu ta ’ 7 ġimgħat, il- pazjenti fejn it- tumur m’ avvanzax, ingħataw ir - radjuterapija (RT), skond il- gwidi stabbiliti, ghal 7 ġimgħat. (TPF/ RT).
Patients on the comparator arm received cisplatin (P) 100 mg/ m2 followed by 5-fluorouracil (F) 1000 mg/ m2 per day for 5 days.
Pazjenti tal- fergħa kompettitiva rċevew cisplatin (P) 100 mg/ m2 segwit minn 5- fluorouracil (F) 1000 mg/ m2 kuljum għal 5 ijiem.
This regimen was administered every three weeks for 4 cycles in case at least a minor response (≥ 25% reduction in bidimensionally measured tumour size) was observed after 2 cycles.
Din is- sistema ta ’ kura ingħatat kull tliet ġimgħat għal 4 ċikli fil- każ li, ta ’ l- anqas, rispons ċkejken kien ikun osservat wara żewġ ċikli (≥ 25% tnaqqis fid- daqs tat- tumur permezz ta ’ kejl f’ żewġ dimensjonijiet).
Efficacy of docetaxel in the induction treatment of patients with inoperable locally advanced SCCHN (Intent-to-Treat Analysis)
67 L- Effikaċja ta ’ docetaxel fit- trattament induttiv ta ’ pazjenti b’ SCCHN inoperabbli u lokalment avvanzat (Analiżi bl- Iskop li Titratta)
Endpoint
docetaxel + Cis+5 - FU
Cis + 5-FU
n
n = 177
= 177 11. 4
n = 181
= 181 8. 3
Median progression free survival (months) (95% CI) Adjusted Hazard ratio
javvanza (xhur) (95% CI)
11.4 (10.1-14.0)
(10. 1- 14. 0)
67 Quality of life parameters Patients treated with TPF experienced significantly less deterioration of their Global health score compared to those treated with PF (p = 0.01, using the EORTC QLQ-C30 scale).
Il- parametri tal- kwalità tal- ħajja Il- pazjenti ittrattati b’ TPF kellhom b’ mod sinifikattiv anqas ta ’ deterjorazzjoni fil- kejl tas- saħħa Globali, meta mqabbla ma ’ dawk ittrattati bi PF (p = 0. 01, meta tintuża l- iskala EORTC QLQ- C30).
Clinical benefit parameters The performance status scale, for head and neck (PSS-HN) subscales designed to measure understandability of speech, ability to eat in public, and normalcy of diet, was significantly in favor of TPF as compared to PF.
Il- parametri tal- benefiċċju kliniku L- iskaletti ta ’ l- iskala ta ’ l- istatus ta ’ kapaċità, għar- ras u l- għonq (PSS- HN), maħduma biex jitkejlu l - ftehim fid- diskors, il- kapaċità biex wieħed jiekol fil- publiku, u jsegwi dieta normali, kienu b’ mod sinifikattiv favur TPF meta mqabbel ma ’ PF.
Patients on the docetaxel arm received docetaxel (T) 75 mg/ m² by intravenous infusion on day 1 followed by cisplatin (P) 100 mg/ m² administered as a 30-minute to three-hour intravenous infusion, followed by the continuous intravenous infusion of 5-fluorouracil (F) 1000 mg/ m²/ day from day 1 to day 4.
Pazjenti tal- fergħa ta ’ docetaxel ingħataw 68 docetaxel (T) 75 mg/ m2 bħala infużjoni fil- vini fl- ewwel jum segwit minn cisplatin (P) 100 mg/ m2 li jingħata bħala infużjoni fil- vini fuq tul ta ’ 30 minuta sa 3 sigħat, segwit minn 5- fluorouracil (F) 1000 mg/ m2 kuljum bħala infużjoni kontinwa minn jum 1 sa jum 4.
All patients who did not have progressive disease were to receive chemoradiotherapy (CRT) as per protocol (TPF/ CRT).
Il- pazjenti kollha fejn it- tumur m’ avvanzax, ingħataw (CRT), skond il - protokol (PF/ CRT).
68 Efficacy of docetaxel in the induction treatment of patients with locally advanced SCCHN (Intent-to-Treat Analysis)
L- Effikaċja ta ’ docetaxel fit- trattament induttiv ta ’ pazjenti b’ SCCHN inoperabbli u lokalment avvanzat (Analiżi bl- Iskop li Titratta)
5.2 Pharmacokinetic properties
69 5. 2 Tagħrif farmakokinetiku
About 80% of the radioactivity recovered in faeces is excreted during the first 48 hours as one major inactive metabolite and 3 minor inactive metabolites and very low amounts of unchanged medicinal product.
Madwar 80% tar- radjuattività irkuprata fl - ippurgar titneħħa waqt l- ewwel 48 siegħa bħala prodott metaboliku inattiv, wieħed ewlieni u tliet prodotti oħra inattivi u minuri, kif ukoll ammonti żgħar ħafna tal- prodotti mediċinali mhux mibdula.
Pharmacokinetic parameters estimated by the model were very close to those estimated from phase I studies.
Il- parametri farmakokinetiċi stmati b’ dan il- mudell kienu viċin ħafna għal dawk stmati mill- istudji fil- Fażi I.
Docetaxel clearance was not
F’ numru żgħir ta ’ pazjenti (n = 23) li kellhom data bijokimiku kliniku suġġestiv ta ’ indebolimenttal - fwied minn grad ħafif sa moderat, (ALT, AST ≥ 1. 5 drabi ta ’ l- OLN assoċjat ma ’ livelli ta ’ l- enzima alkaline phosphatase ≥ 2. 5 drabi ta ’ l- OLN), it- tneħħija totali tbaxxiet b’ medja ta ’ 27% (ara sezzjoni 4. 2).
69 modified in patients with mild to moderate fluid retention and there are no data available in patients with severe fluid retention.
It- tneħħija ta ’ docetaxel ma kienx immodifikat f’ pazjenti bi grad ħafif sa wieħed moderat taż - żamm ta ’ fluwidu, u m’ hemmx data fuq pazjenti bi grad sever taż- żamm ta ’ fluwidu.
The pharmacokinetic profile of cisplatin administered shortly after docetaxel infusion is similar to that observed with cisplatin alone.
Il- profil farmakokinetiku ta ’ cisplatin, li ngħata ftit wara l- infużjoni ta ’ docetaxel, huwa simili għal dak osservat b’ cisplatin waħdu.
Docetaxel has been shown to be mutagenic in the in vitro micronucleus and chromosome aberration test in CHO-K1 cells and in the in vivo micronucleus test in the mouse.
Madankollu,
However, it did not induce mutagenicity in the Ames test or the CHO/ HGPRT gene mutation assay.
70 m’ induċix mutaġeniċita fit- test t’ Ames jew fi studju mutaġeniku tal- ġene CHO/ HGPRT.
• 3 years. • Premix solution:
6. 3 Żmien kemm idum tajjeb il- prodott mediċinali
For storage conditions of the diluted medicinal product, see section 6.3.
Taħżinx f’ temperatura ’ l fuq minn 25 °Ċ jew taħt 2 °Ċ Aħżen fil- pakkett oriġinali sabiex tilqa ’ mid- dawl Għall- kundizzjonijiet ta ’ ħażna tal- prodott mediċinali dilwit, ara sezzjoni 6. 3.
Each blister pack contains: • one single-dose vial of concentrate and, • one single-dose vial of solvent.
Kull pakkett bil- fojl fih: • kunjett b’ doża waħda - ta ’ konċentrat u, • kunjett b’ doża waħda ta ’ solvent ’.
Docetaxel Winthrop 80 mg concentrate for solution for infusion vial
Kunjett ta ’ Docetaxel Winthrop 80 mg konċentrat għal soluzzjoni għall- infużjoni:
15 ml clear glass Type I vial with a red flip-off cap.
Kunjett ta ’ 7 ml magħmul minn ħġieġ ċar tat- Tip I u li għandu tapp aħdar li tista ’ tiftħu billi tgħolliħ.
This vial contains 2 ml of a 40 mg/ ml solution of docetaxel in polysorbate 80 (fill volume:
Dan il- kunjett fih 0. 5 ml ta ’ soluzzjoni ta ’ 40 mg/ ml ta ’ docetaxel f’ polysorbate 80.
94.4 mg/ 2.36 ml).
(Il- volum attwali huwa ta ’ 24. 4 mg/ 0. 61 ml).
This fill volume has been established during the development of Docetaxel Winthrop to compensate for liquid loss during preparation of the premix due to foaming, adhesion to the walls of the vial and "dead-volume".
Dan il- volum attwali, stabbilit waqt l- iżvilupp ta’ Docetaxel Winthrop, qiegħed hemm biex ipatti għat- telf ta ’ likwidu waqt il- preparazzjoni ta ’ soluzzjoni inizjali, dovut għall- formazzjoni ta’ ragħwa, għal dak li jibqa ’ f’ kuntatt mal- ħġieġ tal- kunjett u għall- ammont ċkejken li jibqa ’ fil- flixkun u li ma jkunx jista ’ jitella ’ bil- labra tas- siringa.
This overfill ensures that after dilution with the entire contents of the accompanying solvent for Docetaxel Winthrop vial, there is a minimal extractable premix volume of 8 ml containing 10 mg/ ml docetaxel which corresponds to the labelled amount of 80 mg per vial.
Dan jikkorrispondi għal ammont ta ’ 20 mg imsemmi fuq it- tabella tal- kunjett.
Solvent vial
71 Il- kunjett tas- solvent:
15 ml clear glass Type I vial with a transparent colourless flip-off cap.
Il- kunjett tas- solvent għandu volum ta ’ 7 ml, hi magħmula minn ħġieġ ċar b’ tapp trasparenti bla kulur, li tista ’ tiftħu billi tgħolliħ.
Solvent vial contains 6 ml of a 13% w/ w solution of ethanol 95% in water for injections (fill volume:
Il- kunjett tas- solvent għandu volum ta ’ 1. 5 ml ta ’ 13% (w/ w) ta ’ soluzzjoni ta ’ ethanol 95% fl- ilma għall- injezzjonijiet.
7.33 ml).
(Il- volum attwali huwa ta ’ 1. 98 ml).
The addition of the entire contents of the solvent vial to the contents of the Docetaxel Winthrop 80 mg concentrate for solution for infusion vial ensures a premix concentration of 10 mg/ ml docetaxel.
Meta jiżdied is- solvent kollu fil- kunjett ta’ Docetaxel Winthrop 80 mg konċentrat għal soluzzjoni għall- infużjoni, is- soluzzjoni inizjali li tirriżulta tkun ta ’ 10 mg/ ml docetaxel.
71 Preparation for the intravenous administration
Il- preparazzjoni tal- prodott għall- għoti ġol- vini
Inject the entire contents of the syringe into the corresponding Docetaxel Winthrop vial.
Injetta il- kontenut sħiħ tas- siringa fil- kunjett korrispondenti ta’ Docetaxel Winthrop.
b) Preparation of the infusion solution
b) Preparazzjoni ta ’ soluzzjonigħal- infużjoni