qanastek/EMEA-V3 huggingface dataset:
The results of a meta-analysis of 13 clinical trials with data from over 3800 patients treated with capecitabine showed that in all studies combined, the following covariates were statistically significantly associated with an increased risk of developing diarrhea: increasing capecitabine starting dose (gram), increasing duration of study treatment (weeks), increasing age (by 10 year increments), and female gender.
15 Ir- riżultati ta ’ meta- analiżi ta ’ 13- il prova klinika b’ tagħrif minn aktar minn 3800 pazjent kkurati b’ capecitabine wrew li fl- istudji kollha kombinati, l- kovarjanti li ġejjin kienu assoċjati b’ mod statistikament sinifikanti ma ’ żjieda fir- riskju ta ’ żvilupp ta ’ dijarea: żjieda fid- doża (grammi) tal- bidu ta ’ capecitabine, żjieda fit- tul ta ’ kura taħt studju (ġimgħat), żjieda fl- età (b’ żjidiet ta ’ 10 snin), u sess femminili.
The following covariates were statistically significantly associated with a decreased risk of developing diarrhea: increasing cumulative capecitabine dose (0.1*kg) and increasing relative dose intensity in the first six weeks.
Il- kovarjanti li ġejjin kienu assoċjati b’ mod statistikament sinifikanti ma ’ tnaqqis fir- riskju ta ’ żvilupp ta ’ dijarea: żjieda fid- doża kumulattiva ta ’ capecitabine (0. 1 *) u żjieda fl- intensità tad- doża relattiva fl- ewwel sitt ġimgħat.
Cardiotoxicity (see section 4.4):
Kardjotossiċità (ara sezzjoni 4. 4):
In addition to the ADRs described in Tables 4 and 5, the following ADRs with an incidence of less than 0.1% were associated with the use of Xeloda monotherapy based on a pooled analysis from clinical safety data from 7 clinical trials including 949 patients (2 phase III and 5 phase II clinical trials in metastatic colorectal cancer and metastatic breast cancer): cardiomyopathy, cardiac failure, sudden death, and ventricular extrasystoles.
Barra mill- ADRs deskritti f’ Tabelli 4 u 5, ibbażat fuq analiżi globali minn tagħrif dwar is- sigurtà klinika minn 7 provi kliniċi li kienu jinkludu 949 pazjent (2 provi kliniċi ta ’ fażi III u 5 ta ’ fażi II f’ kanċer metastatiku tal- kolorektum u kanċer metastatiku tas- sider), l- ADRs li ġejjin, b’ inċidenza ta ’ inqas minn 0. 1%, kienu assoċjati ma ’ l- użu ta ’ Xeloda bħala monoterapija: kardjomijopatija, insuffiċjenza kardijaka, mewt f’ daqqa, u ekstrasistoli ventrikulari.
Encephalopathy:
Enċefalopatija:
In addition to the ADRs described in Tables 4 and 5, and based on the above pooled analysis from clinical safety data from 7 clinical trials, encephalopathy was also associated with the use of Xeloda monotherapy with an incidence of less than 0.1%.
Barra mill- ADRs deskritti fit- Tabelli 4 u 5, u bbażat fuq analiżi globali minn tagħrif kliniku dwar is - sigurtà minn 7 provi kliniċi, enċefalopatija wkoll kienet assoċjata ma ’ l- użu ta ’ Xeloda bħala monoterapija b’ inċidenza ta ’ inqas minn 0. 1%.
Elderly patients (see section 4.2):
Pazjenti anzjan (ara sezzjoni 4. 2):
An analysis of safety data in patients ≥ 60 years of age treated with Xeloda monotherapy and an analysis of patients treated with Xeloda plus docetaxel combination therapy showed an increase in the incidence of treatment-related grade 3 and 4 adverse reactions and treatment-related serious adverse
Analiżi ta ’ tagħrif dwar is- sigurtà f’ pazjenti b’ età ta ’ ≥ 60 sena kkurati b’ monoterapija ta ’ Xeloda u analiżi ta ’ pazjenti kkurati b’ terapija mħalta ta ’ Xeloda flimkien ma ’ docetaxel uriet żjieda fl- inċidenza ta ’ reazzjonijiet avversi ta ’ grad 3 u 4 u ta ’ reazzjonijiet avversi serji relatati mal- kura meta mqabbla ma ’ pazjenti b’ età ta ’ < 60 sena.
Patients ≥ 60 years of age treated with Xeloda plus docetaxel also had more early withdrawals from treatment due to adverse reactions compared to patients < 60 years of age.
Barra dan, pazjenti b’ età ta ’ ≥ 60 sena kkurati b’ Xeloda flimkien ma ’ docetaxel kellhom irtirar aktar kmieni mill- kura minħabba reazzjonijiet avversi meta mqabbla ma ’ pazjenti b’ età ta ’ < 60 sena
The results of a meta-analysis of 13 clinical trials with data from over 3800 patients treated with capecitabine showed that in all studies combined, increasing age (by 10 year increments) was statistically significantly associated with an increased risk of developing HFS and diarrhea and with a decreased risk of developing neutropenia.
Ir- riżultati ta ’ meta- analiżi ta ’ 13- il prova klinika b’ tagħrif minn aktar minn 3800 pazjent kkurati b’ capecitabine wrew li fl- istudji kollha kombinati, żjieda fl- età (b’ żjidiet ta ’ 10 snin) kienet assoċjati b’ mod statistikament sinifikanti ma ’ żjieda fir- riskju ta ’ żvilupp ta ’ HFS u dijarea u ma ’ riskju mnaqqas ta ’ żvilupp ta ’ newtropenija.
Gender The results of a meta-analysis of 13 clinical trials with data from over 3800 patients treated with capecitabine showed that in all studies combined, female gender was statistically significantly associated with an increased risk of developing HFS and diarrhea and with a decreased risk of developing neutropenia.
Sess Ir- riżultati ta ’ meta- analiżi ta ’ 13- il prova klinika b’ tagħrif minn aktar minn 3800 pazjent kkurati b’ capecitabine wrew li fl- istudji kollha kombinati, sess femminili kien assoċjati b’ mod statistikament sinifikanti ma ’ żjieda fir- riskju ta ’ żvilupp ta ’ HFS u dijarea u ma ’ riskju mnaqqas ta ’ żvilupp ta ’ newtropenija.
Patients with renal impairment (see section 4.2, 4.4, and 5.2):
Pazjenti b’ indeboliment tal- kliewi (ara sezzjoni 4. 2, 4. 4, u 5. 2):
An analysis of safety data in patients treated with Xeloda monotherapy (colorectal cancer) with baseline renal impairment showed an increase in the incidence of treatment-related grade 3 and 4 adverse reactions compared to patients with normal renal function (36% in patients without renal impairment n=268, vs.
Analiżi ta ’ tagħrif dwar is- sigurtà f’ pazjenti kkurati b’ monoterapija ta ’ Xeloda (kanċer tal- kolon u tar - rektum) u b’ indeboliment tal- kliewi fil- linja bażi, uriet żjieda fl- inċidenza ta ’ reazzjonijiet avversi ta ’ grad 3 u 4 relatati mal- kura meta mqabbla ma ’ pazjenti b’ funzjoni renali normali (36% f’ pazjenti mingħajr indeboliment tal- kliewi n=268, vs.
41% in mild n=257 and 54% in moderate n=59, respectively) (see section 5.2).
41% f’ indeboliment ħafif n=257 u 54% f’ indeboliment moderat n=59, rispettivament) (ara sezzjoni 5. 2).
Patients with moderately impaired renal function show an increased rate of dose reduction (44%) vs.
Pazjenti b’ indeboliment moderat fil- funzjoni renali wrew żjieda fir- rata ta ’ tnaqqis fid- doża (44%) vs.
33% and 32% in patients with no or mild renal impairment and an increase in early withdrawals from treatment (21% withdrawals during the first two cycles) vs.
33% u 32% f’ pazjenti bl- ebda indeboliment jew indeboliment ħafif tal- kliewi, u żjieda ta ’ rtirar kmieni mill- kura (rtirar ta ’ 21% waqt l- ewwel żewġ ċikli) vs.
5% and 8% in patients with no or mild renal impairment.
5% u 8% f’ pazjenti bl- ebda indeboliment jew indeboliment moderat tal- kliewi.
The manifestations of acute overdose include nausea, vomiting, diarrhoea, mucositis, gastrointestinal irritation and bleeding, and bone marrow depression.
Is- sintomi ta ’ doża eċċessiva akuta jinkludu tqalligħ, rimettar, dijarea, mukożite, irritazzjoni gastro - intestinali u fsada, u depressjoni tal- mudullun.
Medical management of overdose should include customary therapeutic and supportive medical interventions aimed at correcting the presenting clinical manifestations and preventing their possible complications.
L- immaniġġjar mediku ta ’ doża eċċessiva għandu jinkludi interventi mediċi u terapewtiċi tas- soltu u li huma maħsuba biex jikkoreġu is- sintomi kliniċi preżenti u biex jevitaw il- kumplikazzjoniet possibbli tagħhom.
Pharmacotherapeutic group: cytostatic (antimetabolite), ATC code:
Kategorija farmakoterapewtika: ċitostatiku (anti- metabolita), Kodiċi ATC:
Capecitabine is a non-cytotoxic fluoropyrimidine carbamate, which functions as an orally administered precursor of the cytotoxic moiety 5-fluorouracil (5-FU).
Capecitabine huwa fluoropyrimidine carbamate mhux ċitotossiku, li jiffunzjona bħala prekursur mogħti mill- ħalq tal- parti tal- molekola ċitotossika 5- fluorouracil (5- FU).
Capecitabine is activated via several enzymatic steps (see section 5.2).
Capecitabine huwa attivat permezz ta ’ diversi passi enżimatiċi (ara sezzjoni 5. 2).
The enzyme involved in the final conversion to 5-FU, thymidine phosphorylase (ThyPase), is found in tumour tissues, but also in normal tissues, albeit usually at lower levels.
L- enżima involuta fil- bidla finali għal 5- FU, thymidine phosphorylase (ThyPase), tinstab f’ tessuti bit- tumur, iżda wkoll f’ tessuti normali, għalkemm is- soltu fl- livell aktar baxx.
In human cancer xenograft models capecitabine demonstrated a synergistic effect in combination with docetaxel, which may be related to the upregulation of thymidine phosphorylase by docetaxel.
F’ mudelli tax- xenograft ta ’ kanċer uman, capecitabine wera effett sinerġistiku meta jittieħed flimkien ma ’ docetaxel, li jista ’ jkun relatat maż- żjieda ta ’ thymidine phosphorylase minn docetaxel.
There is evidence that the metabolism of 5-FU in the anabolic pathway blocks the methylation reaction of deoxyuridylic acid to thymidylic acid, thereby interfering with the synthesis of deoxyribonucleic acid (DNA).
Hemm evidenza li l- metaboliżmu ta ’ 5- FU fis- sensiela ta ’ reazzjonijiet anaboliċi jwaqqaf ir- reazzjoni tal- methylation ta ’ deoxyuridylic acid għal thymidylic acid, u b’ hekk jinterferixxi mas- sintesi ta ’ deoxyribonucleic acid (DNA).
The incorporation of 5-FU also leads to inhibition of RNA and protein synthesis.
L- inkorporazzjoni ta ’ 5- FU twassal wkoll għall- inibizzjoni tas- sintesi ta ’ l- RNA u tal- proteini.
Since DNA and RNA are essential for cell division and growth, the effect of 5-FU may be to create a thymidine deficiency that provokes unbalanced growth and death of a cell.
Billi DNA u RNA huma essenzjali għad- diviżjoni u l- iżvilupp taċ- ċelluli, l - effett tal- 5- FU jista ’ jkun li joħloq defiċjenza ta ’ thymidine li tikkawża żvilupp żbilanċjat u l- mewt taċ- ċellula.
The effects of DNA and RNA deprivation are most marked on those cells which proliferate more rapidly and which metabolise 5-FU at a more rapid rate.
L- effetti ta ’ nuqqas ta ’ DNA u RNA jidhru l- aktar fuq dawk iċ- ċelluli li jipproliferaw l - iżjed malajr u li jimmetabolizzaw 5- FU b’ rata aktar mgħaġġla.
15 Colon and colorectal cancer:
Kanċer fil- kolon u kanċer fil- kolon u fir- rektum:
Adjuvant Therapy with Xeloda in colon cancer Data from one multicentre, randomised, controlled phase III clinical trial in patients with stage III (Dukes’ C) colon cancer supports the use of Xeloda for the adjuvant treatment of patients with colon cancer (XACT Study; M66001).
Terapija Awżiljarja ma ’ Xeloda f’ kanċer fil- kolon Tagħrif minn prova klinika ta ’ fażi III multicentre, randomized u kkontrollata f’ pazjenti b’ kanċer fil - kolon ta ’ stadju III (Dukes ’ C) jissapportja l- użu ta ’ Xeloda għall- kura awżiljarja ta ’ pazjenti b’ kanċer tal- kolon (Studju XACT; M66001).
In this trial, 1987 patients were randomised to treatment with Xeloda (1250 mg/ m2 twice daily for 2 weeks followed by a 1-week rest period and given as 3-week cycles for 24 weeks) or 5-FU and leucovorin (Mayo Clinic regimen:
F’ din il- prova, 1987 pazjent kienu randomised għall- kura b’ Xeloda (1250 mg/ m2 darbtejn kuljum għal ġimagħtejn segwit minn perjodu ta ’ waqfien ta ’ ġimgħa u mogħti bħala ċikli ta ’ 3 ġimgħat għal 24 ġimgħa) jew 5- FU u leucovorin (program ta ’ Mayo Clinic:
20 mg/ m2 leucovorin IV followed by 425 mg/ m2 IV bolus 5-FU, on days 1 to 5, every 28 days for 24 weeks).
20 mg/ m2 leucovorin IV segwit minn 425 mg/ m2 5- FU IV bolus, mill- ewwel sal- ħames jum, kull 28 jum għal 24 ġimgħa).
Xeloda was at least equivalent to IV 5-FU/ LV in disease-free survival in per protocol population (hazard ratio 0.92; 95% CI 0.80- 1.06).
Xeloda kien mill- inqas ekwivalenti għal 5- FU/ LV IV fis- sopravvivenza bla marda fil- protokoll għal kull popolazzjoni (hazard ratio 0. 92; 95% CI 0. 80- 1. 06).
In the all-randomised population, tests for difference of Xeloda vs 5-FU/ LV in disease-free and overall survival showed hazard ratios of 0.88 (95% CI 0.77 – 1.01; p = 0.068) and 0.86 (95% CI 0.74 – 1.01; p = 0.060), respectively.
Fil- popolazzjonijiet randomised kollha, testijiet għad- differenza ta ’ Xeloda vs 5- FU/ LV fis- sopravivenza bla marda u fis - sopravivenza globali wrew hazard ratios ta ’ 0. 88 (95% CI 0. 77 – 1. 01; p = 0. 068) u 0. 86 (95% CI 0. 74 – 1. 01; p = 0. 060), rispettivament.
The median follow up at the time of the analysis was 6.9 years.
Il- medjan tal- vista ta ’ wara fil- ħin ta ’ l- analiżi kien 6. 9 snin.
In a preplanned multivariate Cox analysis, superiority of Xeloda compared with bolus 5-FU/ LV was demonstrated.
F’ analiżi Cox multivarjat, ippjanat minn qabel, kienet dimostrata is- superjorità ta ’ Xeloda meta mqabbel ma ’ 5- FU/ LV bħala bolus.
The following factors were pre-specified in the statistical analysis plan for inclusion in the model: age, time from surgery to randomization, gender, CEA levels at baseline, lymph nodes at baseline, and country.
Il- fatturi li ġejjin kienu speċifikati minn qabel fil- pjan ta ’ analiżi statistika għall- inklużjoni fil- mudell: età, ħin mill- kirurġija sar- randomisation, sess, livelli ta ’ CEA fil - linja bażi, glandoli limfatiċi fil- linja bażi, u pajjiż.
In the all-randomised population, Xeloda was shown to be superior to 5FU/ LV for disease-free survival (hazard ratio 0.849; 95% CI 0.739 - 0.976; p = 0.0212), as well as for overall survival (hazard ratio 0.828; 95% CI 0.705 - 0.971; p = 0.0203).
Fil- popolazzjoni randomised kompletament, Xeloda ntwera li huwa superjuri għal 5- FU/ LV għal sopravivenza mingħajr il- marda (hazard ratio 0. 849; 95% CI 0. 739 - 0. 976; p = 0. 0212), kif ukoll għal sopravivenza totali (hazard ratio 0. 828; 95% CI 0. 705 - 0. 971; p = 0. 0203).
Currently, data on the use of Xeloda in combination with other chemotherapeutic agents in adjuvant therapy of colon cancer is not available.
Bħalissa mhux disponibbli tagħrif dwar l- użu ta ’ Xeloda f’ taħlita ma ’ sustanzi kemjoterapewtiċi fil- kura awżiljarja ta ’ kanċer tal- kolon.
Monotherapy with Xeloda in metastatic colorectal cancer Data from two identically-designed, multicentre, randomised, controlled phase III clinical trials (SO14695; SO14796) support the use of Xeloda for first line treatment of metastatic colorectal cancer.
Monoterapija b’ Xeloda f’ kanċer metastatiku tal- kolon u tar- rektum Informazzjoni minn żewġ provi kliniċi kkontrollati ta ’ fażi 3 iddisinjati b’ mod identiku, multicentre u randomised (SO14695; SO14796), jissapportjaw l- użu ta ’ Xeloda għall- kura primarja ta ’ kanċer metastatiku tal- kolon u tar- rektum.
In these trials, 603 patients were randomised to treatment with Xeloda (1250 mg/ m2 twice daily for 2 weeks followed by a 1-week rest period and given as 3-week cycles).
F’ dawn il- provi, 603 pazjenti kienu randomised għall- kura b’ Xeloda (1250 mg/ m2 darbtejn kuljum għal ġimagħtejn segwiti minn perjodu ta ’ ġimgħa ta ’ waqfien tal- kura u mogħtija bħala ċikli ta ’ 3 ġimgħat).
604 patients were randomised to treatment with 5-FU and leucovorin (Mayo regimen:
604 pazjenti ġew randomised għall- kura b’ 5- FU u leucovorin (kors ta ’ Mayo:
20 mg/ m2 leucovorin IV followed by 425 mg/ m2 IV bolus 5-FU, on days 1 to 5, every 28 days).
20 mg/ m2 leucovorin IV segwit minn 425 mg/ m2 5- FU IV bolus, mill - ewwel sal- ħames jum, kull 28 jum).
The overall objective response rates in the all- randomised population (investigator assessment) were 25.7% (Xeloda) vs.
Ir- rati oġġettivi tar- respons totali fil- popolazzjoni randomised kollha (valutazzjoni investigattiva) kienu ta ’ 25. 7% (Xeloda) vs.
16.7% (Mayo regimen); p < 0.0002.
16. 7% (kors ta ’ Mayo); p < 0. 0002.
The median time to progression was 140 days (Xeloda) vs.
Iż- żmien medju għall- progressjoni kien ta ’ 140 jum (Xeloda) vs.
144 days (Mayo regimen).
144 jum (kors ta ’ Mayo).
Median survival was 392 days (Xeloda) vs.
Is - sopravivenza medja kienet ta ’ 392 jum (Xeloda) vs.
391 days (Mayo regimen).
391 jum (kors ta ’ Mayo).
Currently, no comparative data are available on Xeloda monotherapy in colorectal cancer in comparison with first line combination regimens.
17 informazzjoni komparattiva ma hi disponibbli dwar monoterapija b’ Xeloda f’ kanċer tal- kolon u tar - rektum f’ paragun ma ’ l- ewwel għażla ta ’ kura ta ’ mediċini li jittieħdu flimkien.
16 Combination therapy in first-line treatment of metastatic colorectal cancer Data from a multicentre, randomised, controlled phase III clinical study (NO16966) support the use of Xeloda in combination with oxaliplatin or in combination with oxaliplatin and bevacizumab for the first-line treatment of metastatic colorectal cancer.
Terapija ta ’ taħlita għall- kura preferita ta ’ kanċer metastatiku tal- kolorektum Tagħrif minn studju kliniku multicentre, randomised, ikkontrollat ta ’ fażi III (NO16966) isostni l- użu ta ’ Xeloda f’ taħlita ma ’ oxaliplatin jew f’ taħlita ma ’ oxaliplatin u bevacizumab għall- kura preferita ta ’ kanċer metastatiku tal- kolorektum.
The study contained two parts: an initial 2-arm part in which 634 patients were randomised to two different treatment groups, including XELOX or FOLFOX-4, and a subsequent 2x2 factorial part in which 1401 patients were randomised to four different treatment groups, including XELOX plus placebo, FOLFOX-4 plus placebo, XELOX plus bevacizumab, and FOLFOX-4 plus bevacizumab.
L- istudju kien fih żewġ partijiet: il- parti tal- bidu b’ żewġ gruppi fejn 634 pazjent kienu randomised għal żewġ gruppi ta ’ kura differenti, inkluż XELOX jew FOLFOX - 4, u l- parti ta ’ 2x2 fatturi ta ’ wara fejn 1401 pazjent kienu randomised għal erba ’ gruppi ta ’ kura differenti, inkluż XELOX flimkien ma ’ plaċebo, FOLFOX- 4 flimkien ma ’ plaċebo, XELOX flimkien ma ’ bevacizumab, u FOLFOX- 4 flimkien ma ’ bevacizumab.
See Table 6 for treatment regimens.
Ara Tabella 6 għall- korsijiet ta ’ kura.
Treatment Regimens in Study NO16966 (mCRC) Treatment Starting Dose
ta ’ Kura fl- Istudju NO16966 (mCRC) Kura Doża tal- Bidu 2
Schedule
Skeda
85 mg/ m2 200 mg/ m
85 mg/ m IV 2 hr
Oxaliplatin on Day 1, every 2 weeks Leucovorin on Days 1 and 2, every 2
Oxaliplatin fl- Ewwel Ġurnata, kull ġimagħtejn
FOLFOX-4 +
jew
Bevacizumab
200 mg/ m2 IV 2 hr
5-Fluorouracil
Leucovorin fl- Ewwel u fit- Tieni
400 mg/ m2 IV bolus,
FOLFOX- 4 + 400 mg/ m2 IV bolus, Bevacizumab
5-fluorouracil IV bolus/ infusion,
Ġurnata, kull ġimagħtejn
followed by 600 mg/ m2 IV 22 hr
segwit minn 600 mg / m2 IV 22 hr
each on Days 1 and 2, every 2 weeks
Bolus/ injezzjoni IV ta ’ 5 - fluorouracil, kull wieħed fl- Ewwel u fit- Tieni Ġurnata, kull ġimagħtejn
Placebo or Bevacizumab
Plaċebo jew Bevacizumab
5 mg/ kg IV 30-90 mins
5 mg/ kg IV 30- 90 mins 130 mg/ m2 IV 2 hr
Day 1, prior to FOLFOX-4, every 2 weeks
Fl- Ewwel Ġurnata, qabel FOLFOX - 4, kull ġimagħtejn
XELOX or
XELOX jew
130 mg/ m2 IV 2 hr 2 1000 mg/ m oral
2
Oxaliplatin on Day 1, every 3 weeks Capecitabine oral twice daily for 2
Oxaliplatin Ġurnata, kull 3 ġimgħat Capecitabine mill- ħalq darbtejn
twice daily
darbtejn kuljum
weeks (followed by 1 week off- treatment)
minn ġimgħa waħda mingħajr kura)
7.5 mg/ kg IV 30-90 mins
7. 5 mg/ kg IV 30- 90 mins
Day 1, prior to XELOX, every 3 weeks
Fl- Ewwel Ġurnata, qabel XELOX, kull 3 ġimgħat
IV bolus injection immediately after leucovorin
Injezzjoni bolus IV immedjatament wara leucovorin
Non-inferiority of the XELOX-containing arms compared with the FOLFOX-4-containing arms in the overall comparison was demonstrated in terms of progression-free survival in the eligible patient population and the intent-to-treat population (see Table 7).
F’ paragun globali ntwera li l- gruppi li fihom XELOX ma kienux inferjuri meta mqabbla ma ’ gruppi li fihom FOLFOX- 4 f’ termini ta ’ sopravivenza mingħajr progressjoni fil- popolazzjoni ta ’ pazjenti eliġibbli u tal- popolazzjoni b’ intenzjoni li jiġu kkurati (ara Tabella 7).
The results indicate that XELOX is equivalent to FOLFOX-4 in terms of overall survival (see Table 7).
Ir- riżultati jindikaw li XELOX huwa ekwivalenti għal FOLFOX- 4 f’ termini ta ’ sopravivenza globali (ara Tabella 7).
A comparison of XELOX plus bevacizumab versus FOLFOX-4 plus bevacizumab was a pre-specified exploratory analysis.
Paragun ta ’ XELOX u bevacizumab kontra FOLFOX- 4 u bevacizumab kien analiżi esploratorju speċifikat minn qabel.
In this treatment subgroup comparison, XELOX plus bevacizumab was similar compared to FOLFOX-4 plus bevacizumab in terms of progression-free survival (hazard ratio 1.01; 97.5% CI 0.84 - 1.22).
F’ dan il- paragun ta ’ sottogrupp ta ’ kura, XELOX u bevacizumab kien simili meta mqabbel ma ’ FOLFOX- 4 u bevacizumab f’ termini ta ’ sopravivenza mingħajr progressjoni (hazard ratio 1. 01; 97. 5% CI 0. 84 - 1. 22).
The median follow up at the time of the primary analyses in the intent-to-treat population was 1.5 years; data from analyses following an additional 1 year of follow up are also included in Table 7.
Il- medjan tal- vista ta ’ wara fil- ħin tal- analiżi primarja fil- popolazzjoni b’ intenzjoni li tiġi kkurata kien ta ’ sena punt ħamsa; tagħrif minn analiżi wara sena oħra ta ’ visti ta ’ wara huwa nkluż ukoll f ’ Tabella 11.
However, the on-treatment PFS analysis did not confirm the results of the general PFS and OS analysis: the hazard ratio of XELOX versus FOLFOX-4 was 1.24 with 97.5% CI 1.07 - 1.44.
Madankollu, l- analiżi tal- PFS wara l- kura ma kkonfermax ir- riżultati ta ’ l- analiżi ġenerali tal- PFS u tal- OS: il- hazard ratio ta ’ XELOX kontra FOLFOX- 4 kien ta ’ 1. 24 b’ 97. 5% CI 1. 07 - 1. 44.
Although sensitivity analyses show that differences in regimen schedules and timing of tumor assessments impact the on- treatment PFS analysis, a full explanation for this result has not been found.
Għalkemm analiżi tas- sensittività juri li differenza fl- iskeda tal- kors u fil- ħinijiet ta ’ l - istima tat- tumur ikollhom impatt fuq l- analiżi tal- PFS wara l- kura, ma nstabitx spjegazzjoni kompleta għal dan ir- riżultat.
the non-inferiority analysis of Study NO16966 P R I M A R Y A N A L Y S IS
Riżultati importanti ta ’ l- effikaċja għall- analiżi ta ’ nuqqas ta ’ inferjorità ta ’ NO16966 ANALIŻI PRIMARJA FOLFOX- 4/ FOLFOX- 4+P / XELOX/ XELOX+P / FOLFOX- 4+BV XELOX+BV (EPP *:
N= 1017)
N=1017) 1017)
HR
Studju HR
Population
Popolazzjoni
Median Time to Event (Days)
Ħin Medjan sa l- Avveniment (Ġranet)
(97.5% CI)
(97. 5% CI)
Progression-free Survival
Sopravivenza mingħajr Progressjoni 241
1.05 (0.94; 1.18) 1.04 (0.93; 1.16)
1. 04 (0. 93; 1. 16)
Overall Survival
Sopravivenza Globali
577 581 ADDITIONAL 1 YEAR OF FOLLOW UP
577 581 SENA OĦRA TA ’ VISTI TA ’ WARA
0.97 (0.84; 1.14) 0.96 (0.83; 1.12) HR
0. 97 (0. 84; 1. 14) 0. 96 (0. 83; 1. 12) HR
Progression-free Survival
Sopravivenza mingħajr Progrssjoni
1.02 (0.92; 1.14) 1.01 (0.91; 1.12)
1. 02 (0. 92; 1. 14)
1.00 (0.88; 1.13) 0.99 (0.88; 1.12)
1. 00 (0. 88; 1. 13) 0. 99 (0. 88; 1. 12)
*EPP=eligible patient population; **ITT=intent-to-treat population
* EPP=popolazzjoni ta ’ pazjenti eliġibbli; ** ITT=popolazzjoni b’ intenzjoni li jiġu kkurati
Data from a randomised, controlled phase III study (CAIRO) support the use of Xeloda at a starting dose of 1000 mg/ m2 for 2 weeks every 3 weeks in combination with irinotecan for the first-line treatment of patients with metastatic colorectal cancer.
Tagħrif minn studju randomised u kkontrollat ta ’ fażi III (CAIRO) isostni l- użu ta ’ Xeloda f’ doża tal - bidu ta ’ 1000 mg/ m2 għal ġimagħtejn kull 3 ġimgħat flimkien ma ’ irinotecan għall- kura primarja ta ’ pazjenti b’ kanċer metastatiku tal- kolorektum.
820 Patients were randomized to receive either sequential treatment (n=410) or combination treatment (n=410).
820 pazjent kienu randomized biex jirċievu kura sekwenzjali (n=410) jew kura ta ’ taħlita (n=410).
Sequential treatment consisted of first-line treatment with Xeloda (1250 mg/ m2 twice daily for 14 days), second-line irinotecan (350 mg/ m2 on day 1), and third-line combination of capecitabine (1000 mg/ m2 twice daily for 14 days) with oxaliplatin (130 mg/ m2 on day 1).
Kura sekwenzjali ikkonsistiet minn kura primarja b’ Xeloda (1250 mg/ m2 darbtejn kuljum għal 14- il ġurnata), irinotecan bħala kura sekondarja (350 mg/ m2 fl- ewwel ġurnata), u bħala kura terzjarja taħlita ta ’ capecitabine (1000 mg/ m2 darbtejn kuljum għal 14- il ġurnata) ma ’ oxaliplatin (130 mg/ m2 fl- ewwel ġurnata).
Combination treatment consisted of first-line treatment of Xeloda (1000 mg/ m2 twice daily for 14 days) combined with irinotecan (250 mg / m2 on day 1) (XELIRI) and second-line capecitabine (1000 mg/ m2 twice daily for 14 days) plus oxaliplatin (130 mg/ m2 on day 1).
Kura kombinata ikkonsistiet minn kura primarja b’ Xeloda (1000 mg/ m2 darbtejn kuljum għal 14- il ġurnata) flimkien ma ’ irinotecan (250 mg / m2 fl- ewwel ġurnata) (XELIRI) u capecitabine bħala kura sekondarja (1000 mg/ m2 darbtejn kuljum għal 14- il ġurnata) u oxaliplatin (130 mg/ m2 fl- ewwel ġurnata).
All treatment cycles were administered at intervals of 3 weeks.
Iċ- ċikli kollha ta ’ kura ingħataw f’ intervalli ta ’ 3 ġimgħat.
In first-line treatment the median progression-free survival in the intent-to-treat population was 5.8 months (95%CI 5.1 - 6.2 months) for Xeloda monotherapy and 7.8 months (95%CI 7.0 - 8.3 months; p=0.0002) for XELIRI.
Fil- kura primarja il- medjan tas- sopravivenza mingħajr progessjoni fil- popolazzjoni b’ intenzjoni li jiġu kkurati kien ta ’ 5. 8 xhur (95% CI 5. 1 - 6. 2 xhur) għall- monoterapija b’ Xeloda u 7. 8 xhur (95% CI 7. 0 - 8. 3 xhur; p=0. 0002) għal XELIRI.
Data from an interim analysis of a multicentre, randomised, controlled phase II study (AIO KRK 0604) support the use of Xeloda at a starting dose of 800 mg/ m2 for 2 weeks every 3 weeks in combination with irinotecan and bevacizumab for the first-line treatment of patients with metastatic colorectal cancer.
Tagħrif minn analiżi interim ta ’ studju b’ ħafna ċentri, randomised u kkontrollat ta ’ fażi II (AIO KRK 0604) isostni l- użu ta ’ Xeloda f’ doża tal- bidu ta ’ 800 mg/ m2 għal ġimagħtejn kull 3 ġimgħat flimkien ma ’ irinotecan u bevacizumab għall- kura primarja ta ’ pazjenti b’ kanċer metastatiku tal- kolorektum.
115 Patients were randomised to treatment with Xeloda combined with irinotecan (XELIRI) and bevacizumab:
115- il Pazjent kienu randomised għall- kura b’ Xeloda flimkien ma ’ irinotecan (XELIRI) u bevacizumab:
Xeloda (800 mg/ m2 twice daily for two weeks followed by a 7-day rest period), irinotecan (200 mg/ m2 as a 30 minute infusion on day 1 every 3 weeks), and bevacizumab (7.5 mg/ kg as a 30 to 90 minute infusion on day 1 every 3 weeks); a total of 118 patients were randomised to treatment with Xeloda combined with oxaliplatin plus bevacizumab:
Xeloda (800 mg/ m2 darbtejn kuljum għal ġimagħtejn segwit minn perjodu ta ’ waqfien ta ’ 7 ijiem), irinotecan (200 mg/ m2 bħala infużjoni ta ’ 30 minuta fl- ewwel ġurnata kull 3 ġimgħat), u bevacizumab (7. 5 mg/ kg bħala infużjoni ta ’ 30 sa 90 minuta fl- ewwel ġurnata kull 3 ġimgħat); total ta ’ 118- il pazjent kienu randomised għall- kura b’ Xeloda flimkien ma ’ oxaliplatin u bevacizumab:
Xeloda (1000 mg/ m2 twice daily for two weeks followed by a 7-day rest period), oxaliplatin (130 mg/ m2 as a 2 hour infusion on day 1 every 3 weeks), and bevacizumab (7.5 mg/ kg as a 30 to 90 minute infusion on day 1 every 3 weeks).
Xeloda (1000 mg/ m2 darbtejn kuljum għal ġimagħtejn segwit minn perjodu ta ’ waqfien ta ’ 7 ijiem), oxaliplatin (130 mg/ m2 bħala infużjoni ta ’ sagħtejn fl- ewwel ġurnata kull 3 ġimgħat), u bevacizumab (7. 5 mg/ kg bħala infużjoni ta ’ 30 sa 90 minuta fl- ewwel ġurnata kull 3 ġimgħat).
Progression-free survival at 6 months in the intent-to-treat population was 80% (XELIRI plus bevacizumab) versus 74% (XELOX plus bevacizumab).
Sopravivenza mingħajr progressjoni wara 6 xhur fil- popolazzjoni b’ intenzjoni li jiġu kkurati kienet 80% (XELIRI u bevacizumab) kontra 74% (XELOX u bevacizumab).
Overall response rate (complete response plus partial response) was 45% (XELOX plus bevacizumab) versus 47% (XELIRI plus bevacizumab).
Ir- rata ta ’ rispons globali (rispons komplut u rispons parzjali) kienet 45% (XELOX u bevacizumab) kontra 47% (XELIRI u bevacizumab).
Combination therapy in second-line treatment of metastatic colorectal cancer Data from a multicentre, randomised, controlled phase III clinical study (NO16967) support the use of Xeloda in combination with oxaliplatin for the second-line treatment of metastastic colorectal cancer.
19 Terapija ta ’ taħlita fil- kura tat- tieni linja ta ’ kanċer metastatiku tal- kolorektum Tagħrif minn studju kliniku b’ ħafna ċentri, randomised, ikkontrollat ta ’ fażi III (NO16967) isostni l - użu ta ’ Xeloda f’ taħlita ma ’ oxaliplatin għall- kura tat- tieni linja ta ’ kanċer metastatiku tal- kolorektum.
In this trial, 627 patients with metastatic colorectal carcinoma who have received prior treatment with irinotecan in combination with a fluoropyrimidine regimen as first line therapy were randomised to treatment with XELOX or FOLFOX-4.
F’ din il- prova, 627 pazjent b’ karċinoma metastatika tal- kolorektum li rċevew kura minn qabel b’ irinotecan flimkien ma ’ kors ta ’ fluoropyrimidine bħala kura primarja kienu randomised għall- kura b’ XELOX jew FOLFOX- 4.
XELOX was demonstrated to be non-inferior to
Għall- iskeda ta ’ dożaġġ ta ’ XELOX u FOLFOX- 4 (mingħajr iż- żjieda ta ’ plaċebo jew bevacizumab), irreferi għal Tabella 6.
18 FOLFOX-4 in terms of progression-free survival in the per-protocol population and intent-to-treat population (see Table 8).
Intwera li XELOX ma kienx inferjuri għal FOLFOX- 4 f’ termini ta ’ sopravivenza mingħajr progressjoni fil- popolazzjoni skond protokoll u fil - popolazzjoni b’ intenzjoni li jiġu kkurati (ara Tabella 8).
The results indicate that XELOX is equivalent to FOLFOX-4 in terms of overall survival (see Table 8).
Ir- riżultati jindikaw li XELOX huwa ekwivalenti għal FOLFOX- 4 f’ termini ta ’ sopravivenza globali (ara Tabella 8).
The median follow up at the time of the primary analyses in the intent- to-treat population was 2.1 years; data from analyses following an additional 6 months of follow up are also included in Table 8.
Il- medjan tal- vista ta ’ wara fil- ħin ta ’ l- analiżi primarja fil- popolazzjoni b’ intenzjoni li jiġu kkurati kien ta ’ 2. 1 sena; tagħrif minn analiżi wara 6 xhur oħra ta ’ visti ta ’ wara wkoll huma inklużi f” Tabella 8.
FOLFOX-4
Riżultati importanti ta ’ l- effikaċja għall- analiżi ta ’ nuqqas ta ’ inferjorità ta ’ Studju NO16967 ANALIŻI PRIMARJA FOLFOX- 4 XELOX (PPP *:
N= 314) HR
N=313) 314) HR
Progression-free Survival
Sopravivenza mingħajr Progressjoni
1.03 (0.87; 1.24) 0.97 (0.83; 1.14)
0. 97 (0. 83; 1. 14)
1.07 (0.88; 1.31) 1.03 (0.87; 1.23)
1. 07 (0. 88; 1. 31) 1. 03 (0. 87; 1. 23)
ADDITIONAL 6 MONTHS OF FOLLOW UP HR
6 XHUR OĦRA TA ’ VISTI TA ’ WARA HR
Progression-free Survival
Sopravivenza mingħajr Progrssjoni 154
1.04 (0.87; 1.24) 0.97 (0.83; 1.14)
0. 97 (0. 83; 1. 14)
1.05 (0.88; 1.27) 1.02 (0.86; 1.21)
1. 05 (0. 88; 1. 27) 1. 02 (0. 86; 1. 21)
*PPP=per-protocol population; **ITT=intent-to-treat population
* PPP=popolazzjoni skond il- protokoll; ** ITT= popolazzjoni b’ intenzjoni li jiġu kkurati
Advanced gastric cancer:
Kanċer avvanzat ta ’ l- istonku:
Data from a multicentre, randomised, controlled phase III clinical trial in patients with advanced gastric cancer supports the use of Xeloda for the first-line treatment of advanced gastric cancer (ML17032).
Tagħrif minn prova klinika ta ’ fażi III multicentre, randomised u kkontrollata f’ pazjenti b’ kanċer avvanzat ta ’ l- istonku jissapportja l- użu ta ’ Xeloda għall- kura primarja ta ’ kanċer avvanzat ta ’ l - istonku (ML 17032).
In this trial, 160 patients were randomised to treatment with Xeloda (1000 mg/ m2 twice daily for 2 weeks followed by a 7-day rest period) and cisplatin (80 mg/ m2 as a 2-hour infusion every 3 weeks).
F’ din il- prova, 160 pazjent kienu randomised għall kura b’ Xeloda (1000 mg/ m2 darbtejn kuljum għall- ġimagħtejn segwit minn perjodu ta ’ waqfien ta ’ 7 tijiem) u cisplatin (80 mg/ m2 bħala infużjoni fuq medda ta ’ sagħtejn kull 3 ġimgħat).
A total of 156 patients were randomised to treatment with 5-FU (800 mg/ m2 per day, continuous infusion on days 1 to 5 every 3 weeks) and cisplatin (80 mg/ m2 as a 2-hour infusion on day 1, every 3 weeks).
Total ta ’ 156 pazjent kienu randomised għall - kura b’ 5- FU (800 mg/ m2 kuljum, infużjoni kontinwa fl- ewwel sal- ħames jum kull 3 ġimgħat) u cisplatin (80 mg/ m2 bħala infużjoni fuq medda ta ’ sagħtejn fl- ewwel jum, kull 3 ġimgħat).
Xeloda in combination with cisplatin was non-inferior to 5-FU in combination with cisplatin in terms of progression-free survival in the per protocol analysis (hazard ratio 0.81; 95% CI 0.63 - 1.04).
Xeloda f’ taħlita ma ’ cisplatin ma ’ kienx inferjuri għal 5- FU f’ taħlita ma ’ cisplatin f’ termini ta ’ sopravivenza mingħajr progressjoni f’ analiżi skond il- protokoll (hazard ratio 0. 81; 95% CI 0. 63 - 1. 04).
The median progression-free survival was 5.6 months (Xeloda + cisplatin) versus 5.0 months (5-FU + cisplatin).
Il- medjan tas- sopravivenza mingħajr progressjoni kien ta ’ 5. 6 xhur (Xeloda + cisplatin) versus 5. 0 xhur (5- FU + cisplatin).
The hazard ratio for duration of survival (overall survival) was similar to the hazard ratio for progression-free survival (hazard ratio 0.85; 95% CI 0.64 - 1.13).
Il- hazard ratio għat- tul tas- sopravivenza (sopravivenza totali) kien simili għall- hazard ratio tas- sopravivenza mingħajr progressjoni (hazard ratio 0. 85; 95% CI 0. 64 - 1. 13).
The median duration of survival was 10.5 months (Xeloda + cisplatin) versus 9.3 months (5-FU + cisplatin).
Il- medjan tat- tul tas - sopravivenza kien ta ’ 10. 5 xhur (Xeloda + cisplatin) versus 9. 3 xhur (5- FU + cisplatin).
Data from a randomised multicentre, phase III study comparing capecitabine to 5-FU and oxaliplatin to cisplatin in patients with advanced gastric cancer supports the use of Xeloda for the first-line treatment of advanced gastric cancer (REAL-2).
Tagħrif minn studju ta ’ fazi III randomized u multicentre li qabbel capecitabine ma '5- FU u oxaliplatin ma ’ cisplatin f’ pazjenti b’ kanċer avvanzat ta ’ l- istonku jissapportja l- użu ta ’ Xeloda bħala kura primarja ta ’ kanċer avvanzat ta ’ l- istonku (REAL- 2).
In this trial, 1002 patients were randomised in a 2x2 factorial design to one of the following 4 arms:
F’ dan l- istudju, 1002 pazjent kienu randomised f’ disinn fattorjali ta ’ 2x2 għal wieħed minn dawn l- erba ’ gruppi li ġejjin:
- ECF: epirubicin (50 mg/ m2 as a bolus on day 1 every 3 weeks), cisplatin (60 mg/ m2 as a two
20 ECF: epirubicin (50 mg / m2 bħala bolus fl- ewwel jum kull 3 ġimgħat), cisplatin (60 mg/ m2
hour infusion on day 1 every 3 weeks) and 5-FU (200 mg/ m2 daily given by continuous infusion via a central line).
mogħti bħala infużjoni fuq medda ta ’ sagħtejn fl- ewwel jum kull 3 ġimgħat) u 5- FU (200 mg/ m2 mogħti kuljum bħala infużjoni kontinwa permezz ta ’ linja ċentrali).
- ECX: epirubicin (50 mg/ m2 as a bolus on day 1 every 3 weeks), cisplatin (60 mg/ m2 as a two
ECX: epirubicin (50 mg/ m2 bħala bolus fl- ewwel jum kull 3 ġimgħat), cisplatin (60 mg/ m2
hour infusion on day 1 every 3 weeks), and Xeloda (625 mg/ m2 twice daily continuously).
mogħti bħala infużjoni fuq sagħtejn fl- ewwel jum kull 3 ġimgħat), u Xeloda (625 mg/ m2 darbtejn kuljum b’ mod kontinwu).
- EOF: epirubicin (50 mg/ m2 as a bolus on day 1 every 3 weeks), oxaliplatin (130 mg/ m2 given as
EOF: epirubicin (50 mg/ m2 bħala bolus fl- ewwel jum kull 3 ġimgħat), oxaliplatin (130 mg/ m2
a 2 hour infusion on day 1 every three weeks), and 5-FU (200 mg/ m2 daily given by continuous infusion via a central line).
mogħti bħala infużjoni fuq medda ta ’ sagħtejn fl- ewwel jum kull 3 ġimgħat), u 5- FU (200 mg/ m2 mogħti kuljum bħala infużjoni kontinwa permezz ta ’ linja ċentrali).
- EOX: epirubicin (50 mg/ m2 as a bolus on day 1 every 3 weeks), oxaliplatin (130 mg/ m2 given as
EOX: epirubicin (50 mg/ m2 bħala bolus fl- ewwel jum kull 3 ġimgħat), oxaliplatin (130 mg/ m2
a 2 hour infusion on day 1 every three weeks), and Xeloda (625 mg/ m2 twice daily continuously).
mogħti bħala infużjoni fuq medda ta ’ sagħtejn fl- ewwel jum kull 3 ġimgħat), u Xeloda (625 mg/ m2 darbtejn kuljum b’ mod kontinwu).
19 The primary efficacy analyses in the per protocol population demonstrated non-inferiority in overall survival for capecitabine- vs 5-FU-based regimens (hazard ratio 0.86; 95% CI 0.8 - 0.99) and for oxaliplatin- vs cisplatin-based regimens (hazard ratio 0.92; 95% CI 0.80 - 1.1).
L- analiżi ta ’ effikaċja primarja f’ popolazzjoni skond il- protokoll wriet nuqqas ta ’ inferjorità fis - sopravivenza globali għal capecitabine vs korsijiet ibbażati fuq 5- FU (hazard ratio 0. 86; 95% CI 0. 8 - 0. 99) u għal oxaliplatin vs korsijiet ibbażati fuq cisplatin (hazard ratio 0. 92; 95% CI 0. 80 - 1. 1).
The median overall survival was 10.9 months in capecitabine-based regimens and 9.6 months in 5-FU based regimens.
Il - medjan tas- sopravivenza globali kien ta ’ 10. 9 xhur f’ korsijiet bbażati fuq capecitabine u 9. 6 xhur f’ korsijiet bbażati fuq 5- FU.
The median overall survival was 10.0 months in cisplatin-based regimens and 10.4 months in oxaliplatin-based regimens.
Il- medjan tas- sopravvivenza globali kien ta ’ 10. 0 xhur f’ korsijiet bbażati fuq cisplatin u 10. 4 xhur f’ korsijiet bbażati fuq oxaliplatin.
Xeloda has also been used in combination with oxaliplatin for the treatment of advanced gastric cancer.
Xeloda intuża wkoll f’ taħlita ma ’ oxaliplatin għall- kura ta ’ kanċer avvanzat ta ’ l- istonku.
Studies with Xeloda monotherapy indicate that Xeloda has activity in advanced gastric cancer.
Studji b’ monoterapija ta ’ Xeloda jindikaw li Xeloda għandu attività f’ kanċer avvanzat ta ’ l- istonku.
Colon, colorectal and advanced gastric cancer: meta-analysis A meta-analysis of six clinical trials (studies SO14695, SO14796, M66001, NO16966, NO16967, M17032) supports Xeloda replacing 5-FU in mono- and combination treatment in gastrointestinal cancer.
Kanċer tal- kolon, tal- kolorektum u kanċer avvanzat ta ’ l- istonku: meta- analiżi Meta- analiżi ta ’ sitt provi kliniċi (studji SO14695, SO14796, M66001, NO16966, NO16967, M17032) isostnu is- sostituzzjoni ta ’ 5- FU minn Xeloda f’ kura waħedha u ta ’ taħlita f’ kanċer gastro- intestinali.
The pooled analysis includes 3097 patients treated with Xeloda-containing regimens and 3074 patients treated with 5-FU-containing regimens.
L- analiżi globali tinkludi 3097 pazjent ikkurati b’ korsijiet li fihom Xeloda u 3074 pazjent ikkurati b’ korsijiet li fihom 5- FU.
Median overall survival time was 703 days (95% CI:
Iż- żmien Medjan ta ’ sopravivenza globali kien 703 ijiem (95% CI:
671; 743) in patients treated with Xeloda-containing regimens and 683 days (95% CI:
671; 743) f’ pazjenti kkurati b’ korsijiet li fihom Xeloda u 683 jum (95% CI:
648; 715) in patients treated with 5-FU-containing regimens.
648; 715) f’ pazjenti kkurati b’ korsijiet li fihom 5- FU.
The hazard ratio for overall survival was 0.96 (95% CI:
Il- hazard ratio għas- sopravivenza globali kien 0. 96 (95% CI:
0.90; 1.02) indicating that Xeloda-containing regimens are equivalent to 5-FU-containing regimens.
0. 90; 1. 02) u jindika li korsijiet li fihom Xeloda huma ekwivalenti għall- korsijiet li fihom 5- FU.
Breast cancer:
Kanċer tas- sider:
Combination therapy with Xeloda and docetaxel in locally advanced or metastatic breast cancer Data from one multicentre, randomised, controlled phase III clinical trial support the use of Xeloda in combination with docetaxel for treatment of patients with locally advanced or metastatic breast cancer after failure of cytotoxic chemotherapy, including an anthracycline.
Terapija kombinata b’ Xeloda u docetaxel f’ kanċer avvanzat lokalment jew metastatiku tas- sider Tagħrif minn prova klinika waħda kkontrollata, multicentre u randomised ta ’ fażi III, tissapportja l - uża ta ’ Xeloda flimkien ma ’ docetaxel għall- kura ta ’ pazjenti b’ kanċer tas- sider avvanzat lokalment jew metastatiku wara l- falliment ta ’ kemjoterapija ċitotossika, li tinkludi anthracycline.
In this trial, 255 patients were randomised to treatment with Xeloda (1250 mg/ m2 twice daily for 2 weeks followed by 1-week rest period and docetaxel 75 mg/ m2 as a 1 hour intravenous infusion every 3 weeks).
F’ din il- prova, 255 pazjent ġew randomised għall- kura b’ Xeloda (1250 mg/ m2 darbtejn kuljum għal ġimagħtejn segwit minn perijodu ta ’ ġimgħa ta ’ waqfien tal- kura, u docetaxel 75 mg/ m2 bħala infużjoni fil- vini fuq medda ta ’ siegħa kull 3 ġimgħat).
256 patients were randomised to treatment with docetaxel alone (100 mg/ m2 as a 1 hour intravenous infusion every 3 weeks).
256 pazjent kienu randomised għall- kura b’ docetaxel waħdu (100 mg / m2 bħala infużjoni ġol- vini fuq medda ta ’ siegħa kull 3 ġimgħat).
Survival was superior in the Xeloda + docetaxel combination arm (p=0.0126).
Is- sopravivenza kienet ogħla fil- grupp ta ’ kura kombinata b’ Xeloda u docetaxel (p=0. 0126).
Median survival was 442 days (Xeloda + docetaxel) vs.
Is- sopravivenza medja kienet ta ’ 442 jum (Xeloda + docetaxel) vs.
352 days (docetaxel alone).
352 jum (docetaxel waħdu).
The overall objective response rates in the all-randomised population (investigator assessment) were 41.6% (Xeloda + docetaxel) vs.
Ir- rati oġġettivi tar- respons totali fil - popolazzjoni li ġiet randomised (valutazzjoni investigattiva) kienu ta ’ 41. 6% (Xeloda + docetaxel) vs.
29.7% (docetaxel alone); p = 0.0058.
29. 7% (docetaxel waħdu); p = 0. 0058.
Time to progressive disease was superior in the Xeloda + docetaxel combination arm (p < 0.0001).
Iż- żmien għall- progressjoni tal- marda kien superjuri fil- grupp ta ’ kura kombinata b’ Xeloda u docetaxel (p < 0. 0001).
The median time to progression was 186 days (Xeloda + docetaxel) vs.
Iż- żmien medju għall- progressjoni kien ta ’ 186 jum (Xeloda + docetaxel) vs.
128 days (docetaxel alone).
128 jum (docetaxel waħdu).
Monotherapy with Xeloda after failure of taxanes, anthracycline containing chemotherapy, and for whom anthracycline therapy is not indicated Data from two multicentre phase II clinical trials support the use of Xeloda monotherapy for treatment of patients after failure of taxanes and an anthracycline-containing chemotherapy regimen or for whom further anthracycline therapy is not indicated.
21 Monoterapija b’ Xeloda wara falliment ta ’ taxanes, kemjoterapija li fiha anthracycline, u għal dawk li terapija b’ anthracycline mhix indikata Tagħrif minn żewġ provi kliniċi, multicentre ta ’ fażi II jissapportjaw l- użu ta ’ monoterapija ta ’ Xeloda għall- kura ta ’ pazjenti wara l- falliment ta ’ taxanes u kors ta ’ kemjoterapija li fiha anthracycline jew għal dawk il- pazjenti li għalihom kura b’ anthracycline mhix indikata.
In these trials, a total of 236 patients were treated with Xeloda (1250 mg/ m2 twice daily for 2 weeks followed by 1-week rest period).
F’ dawn il- provi, total ta ’ 236 pazjent kienu kkurati b’ Xeloda (1250 mg/ m2 darbtejn kuljum għal ġimagħtejn segwiti minn perijodu ta ’ waqfien tal- kura ta ’ ġimgħa).
The overall objective response rates (investigator assessment) were 20% (first trial) and 25% (second trial).
Ir- rati oġġettivi tar- respons totali (valutazzjoni investigattiva) kienu ta ’ 20% (l- ewwel prova) u ta ’ 25% (it- tieni prova).
The median time to progression was 93 and 98 days.
Iż- żmien medjan għall- progressjoni kien ta ’ 93 u 98 jum.
Median survival was 384 and 373 days.
Is- sopravivenza medjana kienet ta ’ 384 u 373 jum.
All indications:
Indikazzjonijet kollha:
A meta-analysis of 13 clinical trials with data from over 3800 patients treated with Xeloda monotherapy or Xeloda in combination with different chemotherapy regimens in multiple indications (colon, colorectal, gastric and breast cancer) showed that patients on Xeloda who developed hand-foot syndrome (HFS) had a longer overall survival compared to patients who did not develop HFS: median overall survival 29.0 months (95% CI 26.0; 31.6) vs 15.9 months (95% CI 15.0; 17.0) with a hazard ratio of 0.59 (95% CI 0.54; 0.64).
Meta- analiżi ta ’ 13- il prova klinika b’ tagħrif minn aktar minn 3800 pazjent kkurati b’ Xeloda bħala monoterapija jew Xeloda flimkien ma ’ korsijiet ta ’ kimoterapiji differenti f’ indikazzjonijiet multipli (kanċer tal- kolon, tal- kolorektum, ta ’ l- istonku u tas- sider) wriet li pazjenti fuq Xeloda li żviluppaw is - sindrome ta ’ l- idejn u s- saqajn (HFS) kellhom sopravivenża totali itwal meta mqabbel ma ’ pazjenti li ma żviluppawx HFS: sopravivenza totali medjana 29. 0 xahar (95% CI 26. 0; 31. 6) vs 15. 9- il xahar (95% CI 15. 0; 17. 0) b’ proporzjon ta ’ periklu ta ’ 0. 59 (95% CI 0. 54; 0. 64).
The pharmacokinetics of capecitabine have been evaluated over a dose range of 502-3514 mg/ m2/ day.
Il- farmakokinetika ta ’ capecitabine ġiet ikkalkulata fuq firxa ta ’ doża ta ’ 502- 3514 mg/ m2/ kuljum.
The parameters of capecitabine, 5'-deoxy-5-fluorocytidine (5'-DFCR) and 5'-deoxy-5-fluorouridine (5'-DFUR) measured on days 1 and 14 were similar.
Il - parametri ta ’ capecitabine, 5 '- deoxy- 5- fluorocytidine (5' - DFCR) u 5 '- deoxy- 5- fluorouridine (5' - DFUR) mkejla fl- ewwel u fl- 14- il jum kienu jixxiebħu.
The AUC of 5-FU was 30%-35% higher on day 14.
L- AUC ta ’ 5- FU kienet 30% - 35% ogħla fl- 14- il jum.
Capecitabine dose reduction decreases systemic exposure to 5-FU more than dose-proportionally, due to non-linear pharmacokinetics for the active metabolite.
Tnaqqis fid- doża ta ’ capecitabine tnaqqas l- espożizzjoni sistematika għal 5- FU aktar minn proporzjonali mad- doża, minħabba farmakokinetika mhux linejari għall- metabolit attiv.
Absorption: after oral administration, capecitabine is rapidly and extensively absorbed, followed by extensive conversion to the metabolites, 5'-DFCR and 5'-DFUR.
Assorbiment: wara l- għoti orali, capecitabine jiġi assorbit malajr u b’ mod estensiv, segwit minn bidla estensiva għall- metaboliti, 5 '- DFCR u 5' - DFUR.
Administration with food decreases the rate of capecitabine absorption, but only results in a minor effect on the AUC of 5'-DFUR, and on the AUC of the subsequent metabolite 5-FU.
L- għoti ma ’ l- ikel inaqqas ir- rata ta ’ l- assorbiment ta ’ capecitabine iżda jirriżulta biss f’ effett minuri fuq l- AUC ta ’ 5 '- DFUR, u fuq l- AUC tal- metabolit sussegwenti 5- FU.
At the dose of 1250 mg/ m2 on day 14 with administration after food intake, the peak plasma concentrations (Cmax in µg/ ml) for capecitabine, 5'-DFCR, 5'-DFUR, 5-FU and FBAL were 4.67, 3.05, 12.1, 0.95 and 5.46 respectively.
B’ doża ta ’ 1250 mg/ m2 fl- 14- il jum bl- għoti wara t- teħid ta ’ l- ikel, il - konċentrazzjonijiet massimi fil- plażma (Cmax f’ µg/ ml) ta ’ capecitabine, 5 '- DFCR, 5' - DFUR, 5- FU u FBAL kienu ta ’ 4. 67, 3. 05, 12. 1, 0. 95 u 5. 46 rispettivament.
The time to peak plasma concentrations (Tmax in hours) were 1.50, 2.00, 2.00, 2.00 and 3.34.
Il- ħin għall- konċentrazzjonijiet massimi fil- plażma (Tmax f’ siegħat) kienu ta ’ 1. 50, 2. 00, 2. 00, 2. 00 u 3. 34.
The AUC0-∞ values in μ g• h/ ml were 7.75, 7.24, 24.6, 2.03 and 36.3.
Il- valuri ta ’ AUC0- ∞ f’ μg• h/ ml kienu ta ’ 7. 75, 7. 24, 24. 6, 2. 03 u 36. 3.
Protein binding: in vitro human plasma studies have determined that capecitabine, 5'-DFCR, 5'-DFUR and 5-FU are 54%, 10%, 62% and 10% protein bound, mainly to albumin.
Twaħħil mal- proteini: studji in vitro dwar il- plażma umana wrew li capecitabine, 5 '- DFCR, 5' - DFUR u 5- FU huma 54%, 10%, 62% u 10% mwaħħla mal- proteini, prinċipalment ma ’ l- albumina.
Metabolism: capecitabine is first metabolised by hepatic carboxylesterase to 5'-DFCR, which is then converted to 5'-DFUR by cytidine deaminase, principally located in the liver and tumour tissues.
Metaboliżmu: capecitabine huwa immetabolizzat l- ewwel minn carboxylesterase epatika għal 5 '- DFCR, li wara huwa mibdul fi 5' - DFUR minn cytidine deaminase, li jinsab prinċipalment fil- fwied u fit- tessuti bit- tumur.
Further catalytic activation of 5'-DFUR then occurs by thymidine phosphorylase (ThyPase).
Wara sseħħ aktar attivazzjoni katalitika ta ’ 5 '- DFUR minn thymidine phosphorylase (ThyPase).
The enzymes involved in the catalytic activation are found in tumour tissues but also in normal tissues, albeit usually at lower levels.
L- enżimi involuti fl- attivazzjoni katalitika jinstabu f’ tessuti tat- tumur iżda wkoll f’ tessuti normali, għalkemm is- soltu f’ livelli aktar baxxi.