qanastek/EMEA-V3 huggingface dataset:
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. •
All 3 regimens were administered in combination with prednisone or prednisolone 5 mg twice daily, continuously.
Mitoxantrone 12 mg/ m2 mogħti kull 3 ġimghat għal 10 ċikli. • It- tliet gruppi ħadu l- kimoterapija flimkien ma ’ prednisone jew prednisolone 5 mg darbtejn kuljum, bla waqfien.
Patients who received docetaxel every three weeks demonstrated significantly longer overall survival compared to those treated with mitoxantrone.
Il- pazjenti li rċevew docetaxel kull tliet ġimgħat urew sopravivenza totali b’ mod sinifikattiv itwal, meta mqabbla ma ’ dawk ittrattati b’ mitoxantrone.
The increase in survival seen in the docetaxel weekly arm was not statistically significant compared to the mitoxantrone control arm.
Iż- żieda fis- sopravivenza murija fil- fergħa tal - pazjenti li ħadu docetaxel kull ġimgħa ma kienitx statistikament sinifikanti meta mqabbla mal- fergħa ta ’ kontroll b’ mitoxantrone.
Efficacy endpoints for the docetaxel arms versus the control arm are summarized in the following table:
17. 4
Endpoint
(17. 0- 21. 2)
Docetaxel every Docetaxel every 3 weeks week
(15. 7- 19. 0)
Mitoxantrone every 3 weeks
Il- proporzjon tar- riskju
335 334 18.9 17.4 (17.0-21.2) (15.7-19.0) 0.761 0.912 (0.619-0.936) (0.747-1.113) 0.0094 0.3624 291 282 45.4 47.9 (39.5-51.3) (41.9-53.9) 0.0005 < 0.0001 153 154 34.6 31.2 (27.1-42.7) (24.0-39.1) 0.0107 0.0798 141 134 12.1 8.2 (7.2-18.6) (4.2-14.2) 0.1112 0.5853
95% CI
337 16.5 (14.4-18.6) -- -- -- 300 31.7 (26.4-37.3) -- 157 21.7 (15.5-28.9) -- 137 6.6 (3.0-12.1) --
(0. 619- 0. 936)
*Threshold for statistical significance = 0.0175 **PSA:
(0. 747- 1. 113)
Prostate-Specific Antigen
Prostate- Specific Antigen
Given the fact that docetaxel every week presented a slightly better safety profile than docetaxel every 3 weeks, it is possible that certain patients may benefit from docetaxel every week.
Peress li l- fatt li docetaxel meta ngħata kull ġimgħa wera komportament ta ’ sigurtà daqxejn aħjar, milli meta docetaxel ingħata kull 3 ġimgħat, huwa possibbli li ċerti pazjenti jistgħu jibbenefikaw billi jieħdu docetaxel kull ġimgħa.
No statistical differences were observed between treatment groups for Global Quality of Life.
Ma nstabux differenzi statistikament validi bejn iż- żewġ gruppi ta ’ trattament rigward il Kwalità tal - Ħajja Globali.
29 adenocarcinoma of the gastroesophageal junction, who had not received prior chemotherapy for metastatic disease.
Adenokarċinoma ta ’ l- istonku 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 length of a treatment cycle was 3 weeks for the TCF arm and 4 weeks for the CF arm.
It- tul ta ’ ċiklu ta ’ trattament kien ta ’ 3 ġimgħat fil - fergħa TCF u 4 ġimgħat għal fergħa CF.
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.
Iż -
Time to progression (TTP) was the primary endpoint.
29 żmien li ħa t- tumur biex avvanza (TTP) kien l- aħħar stadju primarju tal- proċess.
The risk reduction of progression was 32.1% and was associated with a significantly longer TTP (p = 0.0004) in favor of the TCF arm.
Ir- riskju fit tnaqqis ta ’ l- avvanz kien ta ’ 32. 1%, u kien assoċjat ma ’ TPP b’ mod sinifikattiv itwal (p = 0. 0004) favur il- fergħa TCF.
Overall survival was also significantly longer (p = 0.0201) in favor of the TCF arm with a risk reduction of mortality of 22.7%.
Is- sopravivenza totali kienet ukoll b’ mod sinifikattiv itwal (p = 0. 0201) favur il- fergħa TCF b’ riskju mnaqqas ta ’ mortalità ta ’ 22. 7%.
Efficacy results are summarized in the following table:
Ir- riżultati ta ’ l- effikaċja huma murija fil- qosor hawn taħt fit - tabella li tmiss:
Efficacy of docetaxel in the treatment of patients with gastric adenocarcinoma
L- Effikaċja ta ’ docetaxel fit- trattament ta ’ pazjenti b’ adenokarċinoma ta ’ l- istonku
Endpoint
L- aħħar stadju tal- proċess
Median TTP (months)
TTP medjan (xhur)
= 221 5.6
= 221 5. 6
= 224 3.7
= 224 3. 7
(4.86-5.91)
(4. 86- 5. 91)
(3.45-4.47)
(3. 45- 4. 47)
Hazard ratio
Il- proporzjon tar- riskju
1.473
1. 473
(95% CI) *p-value
(95% CI) * p- value
(1.189-1.825) 0.0004
(1. 189- 1. 825) 0. 0004
Median survival (months)
Sopravivenza medjana (xhur)
(95% CI) 2-year estimate (%) Hazard ratio
(95% CI) Estimu ta sentejn (%) Il- proporzjon tar- riskju
(8.38-10.58) 18.4
(8. 38- 10. 58) 18. 4
1.293
1. 293
(7.16-9.46) 8.8
(7. 16- 9. 46) 8. 8
(1.041-1.606) 0.0201
(1. 041- 1. 606) 0. 0201
Overall Response Rate (CR+PR) (%) p-value Progressive Disease as Best Overall
Ir- rata totali ta ’ rispons (CR+PR) (%) p- value Mard progressiv bħala l- aħjar rispons totali
36.7
36. 7
25.4 0.0106
25. 4 0. 0106
Response (%) *Unstratified logrank test
(%)
16.7
16. 7
25.9
25. 9
Subgroup analyses across age, gender and race consistently favored the TCF arm compared to the CF arm.
Analiżi tal- gruppi meta wieħed jikkonsidra l- età, is- sess u r- razza tiffavorixxi konsistentement il - fergħa TCF meta mqabbla mal- fergħa CF.
A survival update analysis conducted with a median follow-up time of 41.6 months no longer showed a statistically significant difference although always in favour of the TCF regimen and showed that the benefit of TCF over CF is clearly observed between 18 and 30 months of follow up.
Analiżi aġġornata ta ’ sopravivenza, maħduma fuq osservazzjoni wara l- kura, fuq medda ta ’ żmien medjan ta ’ 41. 6 xhur, ma baqgħetx turi differenza statistikament sinifikanti, iżda dejjem iffavorixiet it - tip ta ’ trattament b’ TCF, u uriet li l- benefiċċju ta ’ TCF fuq CF kien jidher sew bejn it- 18 u t- 30 xahar tal- perijodu ta ’ osservazzjoni wara l- kura.
Overall, quality of life (QoL) and clinical benefit results consistently indicated improvement in favor of the TCF arm.
Il- kwalità sħiħa tal- ħajja (QoL) u r- riżultati tal- benefiċċju kliniku konsistentement indikaw titjib favur il- fergħa ta ’ TCF.
Patients treated with TCF had a longer time to 5% definitive deterioration of global health status on the QLQ-C30 questionnaire (p = 0.0121) and a longer time to definitive worsening of Karnofsky performance status (p = 0.0088) compared to patients treated with CF.
Il- pazjenti ittrattati b’ TCF kellhom żmien itwal biex jaslu għal- deterjorament definittiv ta ’ 5% ta ’ l- istat globali ta ’ saħħa fil- kwestjonarju QLQ- C30 (p = 0. 0121) u żmien itwal biex jeħżienu definittivament skond il- performance status ta ’ Karnofsky (p = 0. 0088), meta mqabbla ma ’ pazjenti ittrattati b’ CF.
Head and neck cancer
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 segwita 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).
In this study, 358 patients with inoperable locally advanced SCCHN, and WHO perfomance status 0 or 1, were randomized to one of two treatment arms.
F’ dan l- istudju, 358 pazjent li kellhom SCCHN inoperabbli u lokalment avvanzat u b’ performance status ta ’ WHO ta ’ 0 jew 1, tqassmu lil waħda miż - żewġ friegħi tat- trattament mingħajr għażla.
Patients on the docetaxel arm received docetaxel (T) 75 mg/ m2 followed by cisplatin (P) 75 mg/ m2 followed by 5-fluorouracil (F) 750 mg/ m2 per day as a continuous infusion for 5 days.
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.
At the end of chemotherapy, with a minimal interval of 4 weeks and a maximal interval of 7 weeks, patients whose disease did not
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).
30 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.
Din
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.
30 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 (PF/ 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 (PF/ RT).
Locoregional therapy with radiation was delivered either with a conventional fraction (1.8 Gy - 2.0 Gy once a day, 5 days per week for a total dose of 66 to 70 Gy), or accelerated/ hyperfractionated regimens of radiation therapy (twice a day, with a minimum interfraction interval of 6 hours, 5 days per week).
It- terapija lokoreġjonali bir- radjazzjoni kienet mogħtija jew permezz ta ’ sistemi ta ’ frazzjoni konvenzjonali (1. 8 Gy - 2. 0 Gy darba kuljum, 5 ijiem fil- ġimgħa sa doża totali ta ’ 66 to 70 Gy), jew bħala terapija ta ’ radjazzjoni mgħaġġla/ iperfrazzjonata (darbtejn kuljum, b’ intervall minimu ta ’ interfraction ta ’ 6 sigħat, 5 ijiem fil- ġimgħa).
A total of 70 Gy was recommended for accelerated regimens and 74 Gy for hyperfractionated schemes.
Total ta ’ 70 Gy kien irrakkomandat għal sistemi ta ’ trattamenti mgħaġġla u 74 Gy ghal skemi iperfrazzjonati.
Surgical resection was allowed following chemotherapy, before or after radiotherapy.
It- tneħħija kirurġika tat- tumur kienet permessa wara l- kimoterapija, qabel jew wara r- radjuterapija.
Patients on the TPF arm received antibiotic prophylaxis with ciprofloxacin 500 mg orally twice daily for 10 days starting on day 5 of each cycle, or equivalent.
Il- pazjenti tal- fergħa ta ’ TPF irċevew il- profilassi bl- antibijotiċi permezz ta ’ ciprofloxacin 500 mg oralment darbtejn kuljum għal 10 ijiem, mibdi fil- hames jum ta ’ kull ċiklu, jew l- ekwivalenti.
The primary endpoint in this study, progression-free survival (PFS), was significantly longer in the TPF arm compared to the PF arm, p = 0.0042 (median PFS:
L- aħħar stadju primarju tal- proċess f’ dan l- istudju, is- sopravivenza mingħajr l- avvanz (PFS), kien b’ mod sinifikattiv itwal tal- fergħa ta ’ TPF, meta mqabbel mal- grupp ta ’ PF, p = 0. 0042 (PFS medjan:
8.3 months respectively) with an overall median follow up time of 33.7 months.
11. 4 kontra 8. 3 xhur, rispettivament) b’ tul ta ’ żmien sħiħ u medjan ta ’ osservazzjoni wara l- kura ta ’ 33. 7 xhur.
Median overall survival was also significantly longer in favor of the TPF arm compared to the PF arm (median OS:
Is- sopravivenza totali u medjana kienet anke b’ mod sinifikattiv itwal fil- każ tal- grupp TPF, meta mqabbel ma ’ dak tal- fergħa PF (OS medjan:
14.5 months respectively) with a 28% risk reduction of mortality, p = 0.0128.
18. 6 kontra 14. 5 xhur, rispettivament), b’ tnaqqis tar- riskju ta ’ mortalità b’ 28%, p = 0. 0128.
Efficacy results are presented in the table below:
Ir - riżultati ta ’ l- effikaċja huma murija fit- tabella hawn taħt:
Efficacy of docetaxel in the induction treatment of patients with inoperable 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)
Docetaxel + Cis + 5-FU
docetaxel + Cis + 5- FU
(95% CI) Adjusted Hazard ratio
javvanza (xhur) (95% CI)
(10.1-14.0)
(10. 1- 14. 0)
(0.55-0.89) 0.0042
(0. 55- 0. 89) 0. 0042
Median survival (months)
Sopravivenza madjana (xhur)
18.6
18. 6
14.5
14. 5
(95% CI) Hazard ratio
(95% CI) Il- proporzjon tar- riskju
(15.7-24.0)
(15. 7- 24. 0)
(11.6-18.7)
(11. 6- 18. 7)
(95% CI) **p-value
(95% CI) ** p- value
(0.56-0.93) 0.0128
(0. 56- 0. 93) 0. 0128
Best overall response to chemotherapy (%)
L- aħjar rizultat sħiħ bil- kimoterapija (%)
67.8
67. 8
53.6
53. 6
(95% CI) ***p-value Best overall response to study treatment
(95% CI) *** p- value L- aħjar rizultat sħiħ bit- trattament studjat
(60.4-74.6)
(60. 4- 74. 6)
0.006
0. 006
(46.0-61.0)
(46. 0- 61. 0)
[chemotherapy +/ - radiotherapy] (%) (95% CI) ***p-value
[kimoterapija + / - radjuterapija] (%) (95% CI) *** p- value It- tul medjan taż- żmien għar- rispons tal -
72.3 (65.1-78.8)
72. 3 (65. 1- 78. 8) n = 128
58.6 (51.0-65.8)
58. 6 (51. 0- 65. 8) n = 106
Median duration of response to chemotherapy ± radiotherapy (months) (95% CI) Hazard ratio
kimoterapija ± radjuterapija (xhur) (95% CI)
n = 128 15.7 (13.4-24.6)
15. 7 (13. 4- 24. 6)
0.72
11. 7 (10. 2- 17. 4)
n = 106 11.7 (10.2-17.4)
Il- proporzjon tar- riskju
(0.52-0.99) 0.0457
(0. 52- 0. 99) 0. 0457
A Hazard ratio of less than 1 favors docetaxel + cisplatin + 5-FU *Cox model (adjustment for Primary tumor site, T and N clinical stages and PSWHO) **Logrank test *** Chi-square test
Proporzjon ta ’ riskju ta ’ anqas minn 1 huwa favur docetaxel + cisplatin + 5- FU * Cox model (aġġustament għas- sit tat- tumur Primarju, T and N stadji kliniċi u PSWHO) ** Logrank test *** Chi- square test
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).
31 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.
31 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.
Median time to first deterioration of WHO performance status was significantly longer in the TPF arm compared to PF.
Iż- żmien medjan ghall- bidu tad- deterjorazzjoni skond l- istatus ta ’ komportament ta ’ WHO kien b’ mod sinifikattiv itwal fil- grupp TPF meta mqabbel ma ’ PF.
Pain intensity score improved during treatment in both groups indicating adequate pain management.
L- iskala ta ’ l- intensità ta ’ l- uġigħ tjiebet waqt it- trattament fiż- żewġ gruppi li jindika l- immaniġġar adegwat ta ’ l- uġigħ.
• Induction chemotherapy followed by chemoradiotherapy (TAX324) The safety and efficacy of docetaxel in the induction treatment of patients with locally advanced squamous cell carcinoma of the head and neck (SCCHN) was evaluated in a randomized, multicenter open-label, phase III, trial (TAX324).
• Kimoterapija Induttiva segwita bi kimoradjuterapija (TAX324) 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) lokalment avvanzat kienu evalwati fil fażi III ta ’ studju, open- label magħmul minn ċentri multipli, u fejn il- pazjenti tqassmu mingħajr għażla (TAX324).
In this study, 501 patients, with locally advanced SCCHN, and a WHO performance status of 0 or 1, were randomized to one of two arms.
F’ dan l- istudju, 501 pazjent li kellhom SCCHN inoperabbli u lokalment avvanzat u b’ performance status ta ’ WHO ta ’ 0 jew 1, tqassmu lil waħda miż- żewġ friegħi tat- trattament mingħajr għażla.
The study population comprised patients with technically unresectable disease, patients with low probability of surgical cure and patients aiming at organ preservation.
Il- popolazzjoni ta ’ l- istudju hija magħmula minn pazjenti b’ marda li teknikalment ma tistax titneħħa, minn pazjenti bi probabilita baxxa ta ’ kura kirurġika u minn pazjenti bi skop ta ’ preservazzjoni ta ’ l- organi.
The efficacy and safety evaluation solely addressed survival endpoints and the success of organ preservation was not formally addressed.
L- effikaċja u s- sigurta ’ konsidrata tindirizza biss l- aħħar studju ta ’ proċess ta ’ sopravivenza u s- suċċess ta preservazzjoni ta ’ l- organi ma kienx indirizzat formalment.
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 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.
The cycles were repeated every 3 weeks for 3 cycles.
Iċ- ċikli ngħataw ripetutament kull tliet ġimgħat għal 3 ċikli..
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 (TPF/ CRT).
Patients on the comparator arm received cisplatin (P) 100 mg/ m² as a 30-minute to three-hour intravenous infusion on day 1 followed by the continuous intravenous infusion of 5-fluorouracil (F) 1000 mg/ m²/ day from day 1 to day 5.
Pazjenti tal- fergħa kompettitiva rċevew cisplatin (P) 100 mg/ m2 bħala infużjoni fil- vini fuq tul ta ’ 30 minuta sa 3 sigħat f’ jum 1, segwit minn 5- fluorouracil (F) 1000 mg/ m2 kuljum bħala infużjoni kontinwa minn jum 1 sa jum 5.
All patients who did not have progressive disease were to receive CRT as per protocol (PF/ CRT).
Il- pazjenti kollha fejn il- marda m’ avvanzatx ingħataw CRT skond il- protokoll (PF/ CRT).
Patients in both treatment arms were to receive 7 weeks of CRT following induction chemotherapy with a minimum interval of 3 weeks and no later than 8 weeks after start of the last cycle (day 22 to day 56 of last cycle).
Pazjenti fi zewġ friegħi tat- trattament ingħataw CRT għal 7 ġimgħat wara il- kimoterapija induttiva, b’ intervall minimu ta ’ 3 ġimgħat u mhux aktar tard minn 8 ġimgħat mill- bidu ta ’ l- aħħar ċiklu (jum 22 sa jum 56 ta ’ l- aħħar ċiklu).
During radiotherapy, carboplatin (AUC 1.5) was given weekly as a one-hour intravenous infusion for a maximum of 7 doses.
Matul ir- radjuterapija, carboplatin (AUC 1. 5) kien jingħata kull ġimgħa bħala infużjoni fil- vini fuq tul ta ’ siegħa sa massimu ta ’ 7 dożi.
Radiation was delivered with megavoltage equipment using once daily fractionation (2 Gy per day, 5 days per week for 7 weeks, for a total dose of 70-72 Gy).
Ir- radjazzjoni kienet mogħtija permess ta ’ apparat megavoltage b’ użu kuljum ta frazzjoni (2 Gy kull jum, 5 jiem fil- ġimgħa għal 7 ġimgħat, għad doża totali ta ’ 70- 72 Gy).
Surgery on the primary site of disease and/ or neck could be considered at anytime following completion of CRT.
Il- kirurġija fuq sit primarju tal- marda u/ jew l- għonq huwa kunsidrat f’ kull ħin wara it- teħid komplet ta ’ CRT.
All patients on the docetaxel-containing arm of the study received prophylactic antibiotics.
Il- pazjenti kollha tal- fergħa ta ’ docetaxel fl- istudju kienu mogħtija antibijotiċi profilatiċi.
The primary efficacy endpoint in this study, overall survival (OS) was significantly longer (log-rank test, p = 0.0058) with the docetaxel-containing regimen compared to PF (median OS:
L- aħħar stadju primarju effikaċju tal- proċess f’ dan l- istudju, l- aħjar sopravivenza (OS), kien b’ mod sinifikattiv itwal (log- rank test, p=0. 0058) fil- fergħa ta ’ docetaxel, meta mqabbel mal- grupp ta ’ PF (OS medjan:
70.6 versus 30.1 months respectively), with a 30% risk reduction in mortality compared to PF (hazard ratio (HR) = 0.70, 95% confidence interval (CI) = 0.54-0.90) with an overall median follow up time of 41.9 months.
70. 6 kontra 30. 1 xhur rispettivament) b’ tnaqqis tar- riskju ta ’ mortalità b’ 30% meta mqabbel ma ’ dak tal- fergħa PF (Il- proporzjon tar- riskju (HR) = 0. 70, 95% confidence interval (CI) = 0. 54- 0. 90) l- aħjar tul medjan tal- perijodu ta ’ osservazzjoni ta ’ 41. 9 xhur.
The secondary endpoint, PFS, demonstrated a 29% risk reduction of progression or death and a 22 month improvement in median PFS (35.5 months for TPF and 13.1 for PF).
L - aħħar stadju sekondarju, PFS, wera tnaqqis tar- riskju mingħajr avvanz u mortalità ta ’ 29% u titjib ta ’ 22 xhur tal- medjan PFS (35. 5 xhur għal TPF u 13. 1 ta ’ PF).
This was also statistically significant with an HR of 0.71; 95% CI 0.56-0.90; log-rank test p = 0.004.
Din kienet ukoll statistikament sinifikanti bi HR ta ’ 0. 71; 95% CI 0. 56- 0. 90; log- rank test p = 0. 004.
Efficacy results are presented in the table below:
Ir- riżultati ta ’ l- effikaċja huma murija fit - tabella hawn taħt:
32 Efficacy of docetaxel in the induction treatment of patients with locally advanced SCCHN (Intent-to-Treat Analysis)
32 L- Effikaċja ta ’ docetaxel fit- trattament induttiv ta ’ pazjenti b’ SCCHN inoperabbli u lokalment avvanzat (Analiżi bl- Iskop li Titratta)
Docetaxel + Cis + 5-FU n = 255
Docetaxel + Cis + 5- FU
Cis + 5-FU n = 246
= 246
Median overall survival (months) (95% CI) Hazard ratio:
(95% CI) Il- proporzjon tar- riskju
70.6 (49.0-NA)
(49. 0- NA)
30.1 (20.9-51.5)
(20. 9- 51. 5)
Median PFS (months)
PFS madjana (xhur)
(95% CI) Hazard ratio:
(95% CI) Il- proporzjon tar- riskju
(10.6 - 20.2)
(10. 6- 20. 2)
(0.56 - 0.90) 0.004
(0. 56- 0. 90) 0. 004
Best overall response (CR + PR) to
L- aħjar rizultat sħiħ (CR + PR) bil- kimoterapija
chemotherapy (%) (95% CI)
(%) (95% CI)
***p-value
*** p- value L- aħjar rizultat sħiħ (CR + PR) bit- trattament
Best overall response (CR + PR) to study treatment [chemotherapy +/ - chemoradiotherapy] (%) (95%CI)
studjat [kimoterapija + / - kimoradjuterapija] (%) (95% CI) *** p- value
71.5 (65.5-77.1)
0. 209
***p-value
71. 5 (65. 5- 77. 1)
A Hazard ratio of less than 1 favors docetaxel + cisplatin + fluorouracil *un-adjusted log-rank test **un-adjusted log-rank test, not adjusted for multiple comparisons ***Chi square test, not adjusted for multiple comparisons NA-not applicable
Proporzjon ta ’ riskju ta ’ anqas minn 1 huwa favur docetaxel + cisplatin + fluorouracil * Log- rank test mhux aġġustat ** Logrank test mhux aġġustat, mhux aġġustat għal paraguni multipli *** Chi- square test, mhux aġġustat għal paraguni multipli NA - Ma jgħoddx f’ dan il- każ.
The pharmacokinetics of docetaxel have been evaluated in cancer patients after administration of 20-115 mg/ m2 in phase I studies.
Il- komportament farmakokinetiku ta ’ docetaxel kien studjat f’ pazjenti bil- kanċer wara l- għoti ta ’ 20 sa 115 mg/ m2 fil- fażi I ta ’ l- istudji.
The kinetic profile of docetaxel is dose independent and consistent with a three-compartment pharmacokinetic model with half lives for the α, β and γ phases of 4 min, 36 min and 11.1 h, respectively.
Il- profil kinetiku ta ’ docetaxel huwa indipendenti mid- doża użata u huwa konsistenti ma ’ mudell farmakokinetiku bi tliet oqsma, biż- zmien kemm idum biex jonqos bin - nofs fil- livell tad- demm għall- fażijiet α, β u γ huwa ta ’ 4 minuti, 36 minuta u 11. 1 sigħat, rispettivament.
The late phase is due, in part, to a relatively slow efflux of docetaxel from the peripheral compartment.
Il- fażi ta ’ l- aħħar hija dovuta partjalment għall- effluss relattivament bil- mod ta ’ docetaxel mill- kompartiment periferika.
Following the administration of a 100 mg/ m2 dose given as a one-hour infusion a mean peak plasma level of 3.7 µg/ ml was obtained with a corresponding AUC of 4.6 h. µg/ ml.
Wara l- għoti ta ’ doża ta ’ 100 mg/ m2 li ngħatat bħala infużjoni fi żmien siegħa, l- ogħla livell medju fil- plażma kien ta ’ 3. 7 μg/ ml b’ AUC korrispondenti ta ’ 4. 6 sigħat. μg/ ml.
Mean values for total body clearance and steady-state volume of distribution were 21 l/ h/ m2 and 113 l, respectively.
Il- valuri medji tat- tneħħija totali mill- ġisem u l- volum ta ’ distribuzzjoni meta jintlaħaq stat stabbli u miżmum kienu 21 l/ siegħa/ m2 u 1131 l, rispettivament.
Inter individual variation in total body clearance was approximately 50%.
Varjazzjoni bejn individwu u ieħor fit- tneħħija totali tas- sustanza mill- ġisem kien ta ’ madwar 50%.
Docetaxel is more than 95% bound to plasma proteins.
Docetaxel huwa iktar minn 95% marbut mal- proteini tal- plażma.
A study of 14C-docetaxel has been conducted in three cancer patients.
Studju b’ 14C- docetaxel sar fi tliet pazjenti bil- kanċer.
Docetaxel was eliminated in both the urine and faeces following cytochrome P450-mediated oxidative metabolism of the tert-butyl ester group, within seven days, the urinary and faecal excretion accounted for about 6% and 75% of the administered radioactivity, respectively.
Dawn ġraw fi żiem sebgħat ijiem u l- ammont imneħħi fl- awrina u fl- ippurgar kienu ta ’ madwar 6% u 75% tar- radjuattività li ngħatat, rispettivament.
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 ta ’ prodott mediċinali mhux mibdula.
A population pharmacokinetic analysis has been performed with docetaxel in 577 patients.
Analiżi farmakokinetika tmexxiet f’ popolazzjoni ta ’ 577 pazjent fuq docetaxel.
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.
The pharmacokinetics of docetaxel were not altered by the age or sex of the patient.
Il - komportmanet farmakokinetiku ta ’ docetaxel ma kienux mibdula mħabba l- età jew is- sess tal- pazjent.
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
33 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.
When used in combination, docetaxel does not influence the clearance of doxorubicin and the plasma levels of doxorubicinol (a doxorubicin metabolite).
Meta ntużaw flimkien, doetaxel ma jeffetwax it- tneħħija ta ’ doxorubicin u anqas l- livelli tal- plasma ta ’ doxorubicinol (prodott metaboliku tad- doxorubicin).
The pharmacokinetics of docetaxel, doxorubicin and cyclophosphamide were not influenced by their coadministration.
Il- komportamenti farmakokinetiċi ta ’ docetaxel, doxorubicin u cyclophosphamide ma kienux effettwati meta ngħataw flimkien.
Phase I study evaluating the effect of capecitabine on the pharmacokinetics of docetaxel and vice versa showed no effect by capecitabine on the pharmacokinetics of docetaxel (Cmax and AUC) and no effect by docetaxel on the pharmacokinetics of a relevant capecitabine metabolite 5’ -DFUR.
Il- capecitabine m’ uriex effett fuq il- komportament farmakokinetiku ta ’ docetaxel (Cmax u l- AUC) u ma kien hemm l- ebda effett minn docetaxel fuq il- komportament farmakokinetiku ta ’ prodott metaboliku 5 ’ - DFUR, rilevanti għal capecitabine.
Clearance of docetaxel in combination therapy with cisplatin was similar to that observed following monotherapy.
It- tneħħija ta ’ docetaxel meta ngħata ma ’ cisplatin kienet l- istess bħal meta ngħata waħdu.
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.
The combined administration of docetaxel, cisplatin and 5-fluorouracil in 12 patients with solid tumors had no influence on the pharmacokinetics of each individual medicinal product.
L- għatien flimkien ta ’ docetaxel, cisplatin u 5- fluorouracil fi 12- il pazjent b’ tumuri solidi ma kellhux effett fuq il- komportament farmakokinetiku ta ’ kull prodott mediċinali individwali.
The effect of prednisone on the pharmacokinetics of docetaxel administered with standard dexamethasone premedication has been studied in 42 patients.
L- effett ta ’ prednisone fuq il- komportament farmakokinetiku ta ’ docetaxel meta ngħata mal - premedikazzjoni ta ’ dexamethasone, bħas- soltu, kien studjat f’ 42 pazjent.
No effect of prednisone on the pharmacokinetics of docetaxel was observed.
Ebda effett ta ’ prednisone fuq il- komportament farmakokinetiku ta ’ docetaxel ma kien innotat.
The carcinogenic potential of docetaxel has not been studied.
Il- potenzjal karċinoġeniku ta ’ docetaxel ma kienx studjat.
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.
Docetaxel intwera li huwa mutaġeniku in vitro fil- mikronukleju u fit- test għall- aberrazzjoni tal - kromosomi fiċ- ċelluli CHO- K1 u fit- test in vivo fuq il- mikronukleju fil- ġurdien.
However, it did not induce mutagenicity in the Ames test or the CHO/ HGPRT gene mutation assay.
Madankollu, m’ induċix mutaġeniċita fit- test t’ Ames jew fi studju mutaġeniku tal- ġene CHO/ HGPRT.
These results are consistent with the pharmacological activity of docetaxel.
Dawn ir - riżultati huma konsistenti ma ’ l- attività farmakoloġika ta ’ docetaxel.
Undesirable effects on the testis observed in rodent toxicity studies suggest that docetaxel may impair male fertility.
L- effetti mhux mixtieqa osservati fuq it- testikola, fit- testijiet ta ’ tossiċità fuq l- annimali gerriema jissuġerixxu li docetaxel jista ’ jinpedixxi l- fertilità tas- sess maskil.
Concentrate vial: polysorbate 80.
Kunjett bis- solvent: ethanol 95% Ilma għall- injezzjonijiet
34 6.3 Shelf-life
34 6. 3 Żmien kemm idum tajjeb il- prodott mediċinali
• 2 years. • Premix solution:
• Sentejn • Soluzzjoni mħallta għal- lest -:
The premix solution contains 10 mg/ ml docetaxel and should be used immediately after preparation.
Is- soluzzjoni tal- bidu għandha 10 mg/ ml docetaxel u għandha tintuża immedjatament wara li tkun kostitwita.
However the chemical and physical stability of the premix solution has been demonstrated for 8 hours when stored either between 2 °C and 8 °C or at room temperature (below 25 °C). • Infusion solution: the infusion solution should be used within 4 hours at room temperature (below 25 °C).
Is- soluzzjoni għall- infuzjoni għandha tintuża fi żmien 4 sigħat f’ temperatura ambjentali (taħt 25 °Ċ).
For storage conditions of the diluted medicinal product, see section 6.3.
Tahżinx 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 20 mg concentrate for solution for infusion vial
Kunjett ta ’ Docetaxel Winthrop 20 mg konċentrat għalsoluzzjoni għall- infużjoni:
7 ml clear glass Type I vial with a green 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 0.5 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.
24.4 mg/ 0.61 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 2 ml containing 10 mg/ ml docetaxel which corresponds to the labelled amount of 20 mg per vial.
Dan jikkorrispondi għal ammont ta ’ 20 mg imsemmi fuq it- tabella tal- kunjett.
Solvent vial
Il- kunjett tas- solvent:
7 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 1.5 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 fl- ilma għall - injezzjonijiet.
1.98 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 20 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 20 mg konċentrat għal soluzzjoni għall- infużjoni, is- soluzzjoni inizjali li tirriżulta tkun ta ’ 10 mg/ ml docetaxel.
Docetaxel Winthrop is an antineoplastic agent and, as with other potentially toxic compounds, caution should be exercised when handling it and preparing Docetaxel Winthrop solutions.
Docetaxel Winthrop hija sustanza kimika għall- użu kontra t- tumuri u, bħal kull sustanza potenzjalment tossika, trid tkun eżerċitata l- kawtela fl- immaniġġar u fil- preparazzjoni tat- taħlitiet ta ’ Docetaxel Winthrop.
The use of gloves is recommended.
L- użu ta ’ l- ingwanti huwa irrakkomandat.
If Docetaxel Winthrop concentrate, premix solution or infusion solution should come into contact with skin, wash immediately and thoroughly with soap and water.
Jekk Docetaxel Winthrop konċentrat, jew is- soluzzjoni ta ’ qabel l- infużjoni, jew l- infużjoni nnifisha tiġi f’ kuntatt mal- ġilda, aħsel immedjatament u sew bis- sapun u l- ilma.
If Docetaxel Winthrop concentrate, premix solution or infusion solution should come into contact with mucous membranes, wash immediately and thoroughly with water.
Jekk Docetaxel Winthrop konċentrat, jew is- soluzzjoni ta ’ qabel l- infużjoni, jew l- infużjoni innifisha tiġi f’ kuntatt mal- mukoża, aħsel immedjatament u sew bl- ilma.
35 Preparation for the intravenous administration
35 Il- preparazzjoni tal- prodott għall- għoti ġol- vini
a) Preparation of the Docetaxel Winthrop premix solution (10 mg docetaxel/ ml)
a) Preparazzjoni ta’ Docetaxel Winthrop, soluzzjoni inizjali (10 mg docetaxel/ ml)
If the vials are stored under refrigeration, allow the required number of Docetaxel Winthrop boxes to stand at room temperature (below 25 °C) for 5 minutes.
Jekk il- kunjetti kienu maħżuna fil- friġġ, ħalli n- numru ta ’ kaxex ta’ Docetaxel Winthrop li għandek bżonn f’ temperatura ambjentali (taħt 25 °Ċ) għal 5 minuti.
Using a syringe fitted with a needle, aseptically withdraw the entire contents of the solvent for Docetaxel Winthrop vial by partially inverting the vial.
Uża siringa b’ labra mwaħħla magħha u tella ’ il- kontenut sħiħ tal- kunjett tas- solvent ta ’ Docetaxel Winthrop, b’ mod asettiku, billi taqleb il- kunjett tas- solvent parzjalment rasu ’ l isfel.
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.
Remove the syringe and needle and mix manually by repeated inversions for at least 45 seconds.
Neħħi s- siringa u l- labra u ħawwad b’ idejk billi ddawwar repetutament il- kunjett rasu ’ l isfel għal mhux inqas minn 45 sekonda.
Do not shake.
Iċċekċikx il- kunjett.
Allow the premix vial to stand for 5 minutes at room temperature (below 25 °C) and then check that the solution is homogenous and clear (foaming is normal even after 5 minutes due to the presence of polysorbate 80 in the formulation).
Ħalli l- kunjett li issa fih is- soluzzjoni inizjali tal- bidu togħqod għal 5 minuti f’ temperatura ambjentali (taħt 25 °Ċ) u ara li t- taħlita hija omoġenja u ċara (il- formazzjoni ta’ ragħwa hija ħaġa normali u tista ’ tibqa ’ anke wara 5 minuti minħabba l- preżenza ta ’ polysorbate 80 fil- formulazzjoni).
The premix solution contains 10 mg/ ml docetaxel and should be used immediately after preparation.
Is- soluzzjoni inizjali għandha 10 mg/ ml docetaxel u għandha tintuża immedjatament wara li tkun ippreparata.
However the chemical and physical stability of the premix solution has been demonstrated for 8 hours when stored either between 2 °C and 8 °C or at room temperature (below 25 °C).
Madankollu, l- istabbiltà kimika u fiżika tas- soluzzjoni inizjali ntweriet li ddum għal 8 sigħat meta tkun maħzuna bejn 2°Ċ u 8°Ċ jew f’ temperatura ambjentali (taħt 25 °Ċ).
b) Preparation of the infusion solution
b) Preparazzjoni ta ’ soluzzjoni għall- infużjoni
More than one premix vial may be necessary to obtain the required dose for the patient.
Jista ’ jagħti l- każ li jkollok tuża aktar minn kunjett wieħed ta ’ konċentrat imħallat biex tilħaq id- doża indikata għall- pazjent.
Based on the required dose for the patient expressed in mg, aseptically withdraw the corresponding premix volume containing 10 mg/ ml docetaxel from the appropriate number of premix vials using graduated syringes fitted with a needle.
Wara li tkun ikkalkulata d- doża għall- pazjent, espressa f’ numru ta ’ milligrammi, u b’ mod asettiku tella ’ l- ammont meħtieġ tas- soluzzjoni inizjali, li issa fiha 10 mg/ ml ta ’ docetaxel, minn numru appropjat ta ’ kunjetti b’ użu ta ’ siringi immarkati bil- labar fil- post.
For example, a dose of 140 mg docetaxel would require 14 ml docetaxel premix solution.
Biex nieħdu eżempju, doża ta ’ 140 mg ta ’ docetaxel tkun tirrikjedi 14 ml ta ’ soluzzjoni inizjali ta ’ docetaxel imħallat u ppreparat mill- konċentrat bis- solvent.
Inject the required premix volume into a 250 ml infusion bag or bottle containing either 5% glucose solution or 0.9% sodium chloride solution.
Injetta l- volum meħtieġ tas- soluzzjoni inizjali tal- bidu f’ borża jew flixkun għall- infużjoni ta ’ 250 ml, li għandha/ għandu soluzzjoni ta ’ 5% glukosju jew 0. 9% kloridu tas- sodju.
If a dose greater than 200 mg of docetaxel is required, use a larger volume of the infusion vehicle so that a concentration of 0.74 mg/ ml docetaxel is not exceeded.
Jekk hija meħtieġa doża akbar minn 200 mg ta ’ docetaxel, uża volum t’ infużjoni akbar biex tiżgura li ma teċċedix il- konċentrazzjoni ta ’ 0. 74 mg/ ml ta ’ docetaxel.
Mix the infusion bag or bottle manually using a rocking motion.
Ħawwad il- borża jew il- flixkun ta ’ l- infużjoni b’ idejk billi iċċaqlaqha/ iċċaqalqu minn naħa għall- oħra.
The Docetaxel Winthrop infusion solution should be used within 4 hours and should be aseptically administered as a 1-hour infusion under room temperature (below 25 °C) and normal lighting conditions.
Is- soluzzjoni għall- infużjoni ta ’ Docetaxel Winthrop għandha tintuża fi żmien 4 sigħat u għandha tingħata b’ mod asettiku bħala infużjoni fuq tul ta ’ siegħa f’ temperatura ambjentali (taħt 25 °Ċ) u f’ dawl normali.
As with all parenteral products, Docetaxel Winthrop premix solution and infusion solution should be visually inspected prior to use, solutions containing a precipitate should be discarded.
Bħall- prodotti kollha parenterali, is- soluzzjoni mħallta lesta ta ’ Docetaxel Winthrop u s- soluzzjoni għall- infużjoni likwida għall- użu għandhom ikunu eżaminati viżwalment qabel l- użu; is- soluzzjonijiet li juru xi partikoli jew frak żgħir m’ għandhomx jintużaw.
Aventis Pharma S. A., 20 avenue Raymond Aron, 92165 Antony Cedex, France
Aventis Pharma S. A., 20, avenue Raymond Aron, 92165 Antony Cedex, Franza
Docetaxel Winthrop 80 mg concentrate and solvent for solution for infusion
Docetaxel Winthrop 80 mg konċentrat u solvent għal soluzzjoni għall- infużjoni
Each single-dose vial of Docetaxel Winthrop 80 mg concentrate contains docetaxel which is a trihydrate corresponding to 80 mg of docetaxel (anhydrous).
Kull kunjett b’ doża waħda ta ’ Docetaxel Winthrop 80 mg, konċentrat, li fih docetaxel li huwa tri- idrat, korrispondenti għal 80 mg ta ’ docetaxel (anidru).
Docetaxel Winthrop in combination with doxorubicin and cyclophosphamide is indicated for the adjuvant treatment of patients with operable node- positive breast cancer.
Docetaxel Winthrop) flimkien ma ’ doxorubicin u cyclophosphamide huwa indikat għat- trattament miżjud f’ pazjenti li għandhom kanċer operabbli, u li nfirex fil- glandoli limfatiċi, tas- sider.
Docetaxel Winthrop is indicated for the treatment of patients with locally advanced or metastatic non- small cell lung cancer after failure of prior chemotherapy.
Kanċer tal- pulmun mhux ta ’ l- għamla ta ’ ċelluli żgħar
Docetaxel Winthrop in combination with cisplatin is indicated for the treatment of patients with unresectable, locally advanced or metastatic non-small cell lung cancer, in patients who have not previously received chemotherapy for this condition.
Docetaxel Winthrop huwa indikat għat- trattament ta ’ pazjenti b’ kanċer tal- pulmun lokalment avvanzat jew dak metastatiku li mhux ta ’ ċelluli żgħar wara falliment ta ’ kimoterapija ċitotossika li ngħatat qabel.
38 Prostate cancer
38 Docetaxel Winthrop flimkien ma ’ cisplatin huwa indikat għat- trattament ta ’ pazjenti b’ kanċer tal - pulmun lokalment avvanzat jew dak metastatiku li mhux ta ’ ċelluli żgħar u li ma jistax jitneħħa f’ pazjenti li ma kinux ħadu qabel terapija ċitotossika għal din il- marda.
Docetaxel Winthrop in combination with cisplatin and 5-fluorouracil is indicated for the induction treatment of patients with locally advanced squamous cell carcinoma of the head and neck.
Docetaxel Winthrop flimkien ma ’ cisplatin u 5- fluorouracil huwa indikat għat- trattament induttiv f’ pazjenti b’ kanċer tat- tip squamous tal- ġilda,, lokalment avvanzat, tar- ras u l- għonq.
Recommended dose
Doża irrakkomandat:
For the treatment of patients with locally advanced or metastatic breast cancer, the recommended dose of docetaxel is 100 mg/ m2 in monotherapy.
Fit- trattament ta ’ pazjenti li għandhom kanċer tas- sider lokalment avvanzat jew dak metastatiku, id - doża irrakkomandata ta ’ docetaxel huwa 100 mg/ m2 meta jintuża waħdu.
For treatment
Kanċer tal- pulmun fejn iċ ċelluli m’ humiex żgħar F’ pazjenti li qatt ma ħadu l- kimoterapija qabel u li qed jiġu ikkurati għall- kanċer tal- pulmun li mhux ta ’ ċelluli żgħar, is- sistema tad- dożaġġi irrakkomandata hija docetaxel 75 mg/ m2 segwit immedjatament b’ cisplatin 75 mg/ m2 fuq perjodu ta ’ bejn 30 u 60 minuta.
39 after failure of prior platinum-based chemotherapy, the recommended dose is 75 mg/ m² as a single agent.
Għall- kura fejn il - kimoterapija preċedenti ibbażata fuq il- platinum falliet, id- doża irrakkomandata hija ta ’ 75 mg/ m2 bħala sustanza waħda.
General Docetaxel should be administered when the neutrophil count is ≥ 1,500 cells/ mm3.
Ġenerali Docetaxel għandu jingħata meta l- għadd taċ- ċelluli newtrofiliċi fid- demm huwa ≥1, 500 ċelluli/ mm3.
In patients who experienced either febrile neutropenia, neutrophil < 500 cells/ mm3 for more than one week, severe or cumulative cutaneous reactions or severe peripheral neuropathy during docetaxel therapy, the dose of docetaxel should be reduced from 100 mg/ m2 to 75 mg/ m2 and/ or from 75 to 60 mg/ m².
F’ pazjenti li kellhom jew id- deni flimkien man- newtropenija, b’ numru ta ’ < 500 ċelluli/ mm3 għal aktar minn ġimgħa, jew reazzjonijiet severi jew kumulattivi fil- ġilda, jew newropatija severa u periferika, waqt it- terapija bid- docetaxel, id- doża ta ’ docetaxel trid titnaqqas minn 100 mg/ m2 għal 75 mg/ m2
Adjuvant therapy for breast cancer In the pivotal trial in patients who received adjuvant therapy for breast cancer and who experienced complicated neutropenia (including prolonged neutropenia, febrile neutropenia, or infection), it was recommended to use G-CSF to provide prophylactic coverage (eg, day 4 to 11) in all subsequent cycles.
Terapija miżjuda għal kanċer tas- sider Fil- prova tal- pern f’ pazjenti li ħadu terapija miżjuda għall- kanċer tas- sider u li kellhom newtropenija b’ komplikazzjonijiet (inklużi n- newtropenija fit- tul u n- newtrpenija akkompanjata bid- deni, jew l - infezzjoni), kien irrakkomandat l- użu ta ’ G- CSF biex jipprovdi protezzjoni profilattika (e. g. ir- 4 jum sal- 11- il jum) fiċ - ċikli kollha sussegwenti.
40 However, in clinical practice neutropenia could occur earlier.
Madankollu, fil- prattika klinika, in- newtropenija tista ’ tiġri qabel.
In combination with cisplatin For patients who are dosed initially at docetaxel 75 mg/ m2 in combination with cisplatin and whose nadir of platelet count during the previous course of therapy is < 25,000 cells/ mm3, or in patients who experience febrile neutropenia, or in patients with serious non-hematologic toxicities, the docetaxel dose in subsequent cycles should be reduced to 65 mg/ m2.
F’ dawk il- pazjenti li fil- bidu qegħdin jieħdu docetaxel 75 mg/ m2, flimkien ma ’ cisplatin, u meta l - għadd tal- plejtlits laħaq il- livell baxx (in- nadir) ta ’ < 25, 000 ċelluli/ mm3, waqt il- kors preċedenti ta ’ terapija, jew f’ pazjenti li jiżviluppaw id- deni flimkien ma ’ newtropenija, jew f’ dawk il- pazjenti li għandhom effetti tossiċi u serji mhux ematoloġiċi, id- doża ta ’ docetaxel f ’ sussegwenti għandha titnaqqas għal 65 mg/ m2.