natgillin/translations-raw huggingface dataset:
Hypertensive encephalopathy (very rare) (see also section 4.4 Special warnings and precautions for use, and Hypertension in section 4.8 Undesirable Effects)
hipertenzivna encefalopatija (zelo redko) (glejte tudi poglavje 4. 4 Bolezni živčevja Posebna opozorila in previdnostni ukrepi in odstavek Hipertenzija v poglavju 4. 8 Neželeni učinki) sindrom reverzibilne posteriorne levkoencefalopatije (redko) (glejte tudi poglavje 4. 4 Posebna opozorila in previdnostni ukrepi)
Renal Thrombotic Microangiopathy, clinically manifested as proteinuria (frequency not known).
Renalna trombotična mikroangiopatija, ki se klinično izrazi kot Žilne bolezni proteinurija (pogostnost ni znana).
For further information on proteinuria see section 4.4 Special warnings and precautions for use, and Proteinuria in section 4.8 Undesirable Effects.
Za dodatne informacije glede proteinurije glejte poglavje 4. 4 Posebna opozorila in previdnostni ukrepi in poglavje 4. 8 Neželeni učinki.
Dysphonia (common) * if specified, the frequency has been derived from clinical trial data
perforacija nosnega pretina (ni znano) Bolezni dihal, prsnega koša in pljučna hipertenzija (ni znano) mediastinalnega disfonija (pogosto) prostora * Kjer je pogostnost navedena, so jo pridobili iz podatkov kliničnih preskušanj.
4.9 Overdose
12 4. 9 Preveliko odmerjanje
The highest dose tested in humans (20 mg/ kg of body weight, intravenous every 2 weeks) was associated with severe migraine in several patients.
Največji odmerek, ki so ga preizkušali pri ljudeh (20 mg/ kg telesne mase, intravensko na 2 tedna), je bil pri nekaj bolnikih povezan s hudo migreno.
Antineoplastic agents, monoclonal antibody, ATC code:
Oznaka ATC:
Mechanism of action Bevacizumab binds to vascular endothelial growth factor (VEGF), the key driver of vasculogenesis and angiogenesis, and thereby inhibits the binding of VEGF to its receptors, Flt-1 (VEGFR-1) and KDR (VEGFR-2), on the surface of endothelial cells.
Mehanizem delovanja Bevacizumab se veže na vaskularni endotelijski rastni faktor (VEGF - vascular endothelial growth factor), ki je ključni dejavnik vaskulogeneze in angiogeneze, in s tem zavira vezavo VEGF na njegova receptorja Flt- 1 (VEGFR- 1) in KDR (VEGFR- 2) na površini endotelijskih celic.
Neutralising the biological activity of VEGF regresses the vascularisation of tumours, normalises remaining tumour vasculature, and inhibits the formation of new tumour vasculature, thereby inhibiting tumour growth.
S tem se rast tumorja zavre.
Pharmacodynamic effects Administration of bevacizumab or its parental murine antibody to xenotransplant models of cancer in nude mice resulted in extensive anti-tumour activity in human cancers, including colon, breast, pancreas and prostate.
Farmakodinamični učinki Injiciranje bevacizumaba ali njegovega izvornega murinskega protitelesa v ksenotransplantantne modele raka pri golih miškah je povzročilo široko antitumorsko aktivnost v tumorju človeškega izvora, vključno z rakom debelega črevesa, dojke, pankreasa in prostate.
12 Clinical efficacy
Klinična učinkovitost
The safety and efficacy of the recommended dose (5 mg/ kg of body weight every two weeks) in metastatic carcinoma of the colon or rectum were studied in three randomised, active-controlled clinical trials in combination with fluoropyrimidine-based first-line chemotherapy.
Varnost in učinkovitost priporočenega odmerka (5 mg/ kg telesne mase vsaka dva tedna) v kombinaciji s kemoterapijo prve izbire na osnovi fluoropirimidina so proučevali v treh randomiziranih, aktivno kontroliranih kliničnih preskušanjih pri bolnikih z metastatskim rakom debelega črevesa in danke.
A weekly schedule of irinotecan/ bolus 5-fluorouracil/ folinic acid (IFL) for a total of 4 weeks of each 6 week-cycle (Saltz regimen). • AVF0780g:
• AVF2107g: tedenska shema irinotekana/ bolusa 5- fluorouracila/ folinske kisline (IFL), ki jo bolnik prejema 4 tedne zapored v 6- tedenskih ciklih (shema Saltz). • AVF0780g: v kombinaciji z bolusom 5- fluorouracila/ folinske kisline (5- FU/ FA).
In combination with bolus 5-fluorouracil/ folinic acid (5-FU/ FA) for a total of 6 weeks of each 8 week-cycle (Roswell Park regimen). • AVF2192g:
Bolnik prejema shemo skupaj 6 tednov v 8- tedenskih ciklih (shema Roswell Park). • AVF2192g: v kombinaciji z bolusom 5- FU/ FA.
In combination with bolus 5-FU/ FA for a total of 6 weeks of each 8 week-cycle (Roswell Park regimen) in patients who were not optimal candidates for first-line irinotecan treatment.
Shemo prejemajo bolniki, ki niso bili najprimernejši za prvo linijo zdravljenja z irinotekanom, in sicer skupaj 6 tednov v 8- tedenskih ciklih (shema Roswell Park).
Two additional studies were conducted in first (NO16966) and second line (E3200) treatment of metastatic carcinoma of the colon or rectum, with Avastin administered in the following dosing regimens, in combination with FOLFOX-4 (5FU/ LV/ Oxaliplatin) and XELOX (Capecitabine/ Oxaliplatin):
V prvi (NO16966) in drugi liniji (E3200) zdravljenja metastatskega raka debelega črevesa in danke so izvedli dve dodatni študiji, pri čemer so zdravilo Avastin v kombinaciji s shemo FOLFOX- 4 (5 - FU/ LV/ oksaliplatin) in shemo XELOX (kapecitabin/ oksaliplatin) aplicirali po naslednji shemi odmerjanja:
Avastin 7.5 mg/ kg of body weight every 3 weeks in combination with oral capecitabine and intravenous oxaliplatin (XELOX) or Avastin 5 mg/ kg every 2 weeks in combination with leucovorin plus 5-fluorouracil bolus, followed by 5-fluorouracil infusion, with intravenous oxaliplatin (FOLFOX-4).
• NO16966: zdravilo Avastin 7, 5 mg/ kg telesne mase vsake 3 tedne v kombinaciji s kapecitabinom peroralno in oksaliplatinom intravensko (shema XELOX) ali zdravilo Avastin 5 mg/ kg telesne mase vsaka 2 tedna v kombinaciji z levkovorinom in bolusom 5- fluorouracila, sledila je infuzija 5- fluorouracila z oksaliplatinom intravensko (shema FOLFOX- 4).
Avastin 10 mg/ kg of body weight every 2 weeks in combination with leucovorin and 5-fluorouracil bolus, followed by 5-fluorouracil infusion, with intravenous oxaliplatin (FOLFOX-4).
• E3200: zdravilo Avastin 10 mg/ kg telesne mase enkrat na 2 tedna v kombinaciji z levkovorinom in bolusom 5- fluorouracila, sledila je infuzija 5- fluorouracila z oksaliplatinom intravensko (shema FOLFOX- 4).
Eight hundred and thirteen patients were randomised to receive IFL + placebo (Arm 1) or IFL + Avastin (5 mg/ kg every 2 weeks, Arm 2).
Randomiziranih je bilo 813 bolnikov, ki so prejeli IFL + placebo (skupina 1) ali IFL + Avastin (5 mg/ kg vsaka 2 tedna, skupina 2).
A third group of 110 patients received bolus 5-FU/ FA+Avastin (Arm3).
Tretja skupina 110 bolnikov je prejela bolus 5- FU/ FA + Avastin (skupina 3).
Enrollment in Arm 3 was discontinued, as pre-specified, once safety of Avastin with the IFL regimen was established and considered acceptable.
Ko je bila varnost kombinacije IFL in zdravila Avastin dokazana in sprejeta, je bilo vključevanje v tretjo skupino prekinjeno, kot je bilo že prej predvideno.
All treatments were continued until disease progression.
Vsa zdravljenja so izvajali dokler ni bolezen napredovala.
The overall mean age was 59.4 years; 56.6% of patients had an ECOG performance status of 0, 43% had a value of 1 and 0.4% had a value of 2.
Celokupna povprečna starost je bila 59, 4 let; splošno stanje zmogljivosti po ECOG (Eastern Cooperative Oncology Group) so pri 56, 6% bolnikov ocenili z 0, pri 43% z 1, pri 0, 4% pa z 2.
15.5% had received prior radiotherapy and 28.4% prior chemotherapy.
15, 5% jih je predhodno prejemalo radioterapijo, 28, 4% pa kemoterapijo.
The addition of Avastin to IFL resulted in statistically significant increases in overall survival, progression-free survival and overall response rate (see Table 3).
Dodatek zdravila Avastin k shemi IFL je statistično značilno podaljšal celokupno preživetje, preživetje brez napredovanja bolezni in celokupen odgovor na zdravljenje teh bolnikov (glejte preglednico 3).
The clinical benefit, as measured by overall survival, was seen in all pre-specified patient subgroups, including those defined by age, sex, performance status, location of primary tumour, number of organs involved and duration of metastatic disease.
Klinična korist, katere merilo je bilo celokupno preživetje, se je pokazala pri vseh že prej izbranih podskupinah, vključno s podskupinami osnovanimi glede na starost, spol, splošno stanje zmogljivosti, lokalizacijo primarnega tumorja, število prizadetih organov in trajanje metastatske bolezni.
The efficacy results of Avastin in combination with IFL-chemotherapy are displayed in Table 3.
Preglednica 3.
Efficacy results for study AVF2107g
Rezultati študije AVF2107g glede učinkovitosti
Number of Patients Overall survival
IFL + Avastina IFL + placebo
IFL
Število bolnikov Celokupno preživetje
95% Confidence Interval b
95 -% interval zaupanja
18.46 – 24.18
18, 46– 24, 18
Hazard ratio
razmerje ogroženostib
(p-value = 0.00004) Progression-free survival
(p- vrednost = 0, 00004) Preživetje brez napredovanja bolezni
Median time (months) Hazard ratio
mediana časa (meseci) razmerje ogroženosti
(p-value < 0.0001)
(p- vrednost < 0, 0001)
44.8
(p- vrednost = 0, 0036)
Relative to control arm.
5 mg/ kg vsake 2 tedna b glede na kontrolno skupino
Among the 110 patients randomised to Arm 3 (5-FU/ FA + Avastin) prior to discontinuation of this arm, the median overall survival was 18.3 months and the median progression free survival was 8.8 months.
Med 110 bolniki, randomiziranimi v skupino 3 (5- FU/ FA + Avastin), je bila mediana celokupnega preživetja pred ukinitvijo te skupine 18, 3 meseca, mediana preživetja brez napredovanja bolezni pa 8, 8 meseca.
This was a phase II randomised, double-blind, active-controlled clinical trial evaluating the efficacy and safety of Avastin in combination with 5-FU/ FA as first-line treatment for metastatic colorectal cancer in patients who were not optimal candidates for first-line irinotecan treatment.
To je bilo randomizirano, aktivno kontrolirano, dvojno slepo klinično preskušanje faze II, v katerem so proučevali učinkovitost in varnost zdravila Avastin v kombinaciji s kemoterapevtsko shemo 5- FU/ FA v prvi liniji zdravljenja bolnikov z metastatskim rakom debelega črevesa in danke, ki niso bili najprimernejši kandidati za prvo linijo zdravljenja z irinotekanom.
One hundred and five patients were randomised to 5-FU/ FA + placebo arm and 104 patients to 5-FU/ FA + Avastin (5 mg/ kg every 2 weeks) arm.
Randomiziranih je bilo 105 bolnikov, ki so prejeli 5- FU/ FA + placebo, in 104 bolniki, ki so prejeli 5- FU/ FA + Avastin (5 mg/ kg vsaka dva tedna).
The addition of Avastin 5 mg/ kg every two weeks to 5-FU/ FA resulted in higher objective response rates, significantly longer progression-free survival, and a trend in longer survival as compared to 5-FU/ FA chemotherapy alone.
Dodatek 5 mg zdravila Avastin/ kg telesne mase vsake dva tedna h kemoterapiji po shemi 5- FU/ FA je povečal objektivni odgovor na zdravljenje in značilno podaljšal preživetje brez napredovanja bolezni.
This was a phase II randomised, active-controlled, open-labelled clinical trial investigating Avastin in combination with 5-FU/ FA as first-line treatment of metastatic colorectal cancer.
AVF0780g: to je bilo randomizirano, aktivno kontrolirano, odprto klinično preskušanje faze II, v katerem so proučevali kombinacijo zdravila Avastin s 5- FU/ FA kot prvo linijo zdravljenja metastatskega raka debelega črevesa in danke.
19% of the patients had received prior chemotherapy and 14% prior radiotherapy.
19% teh bolnikov je predhodno prejemalo kemoterapijo, 14% pa radioterapijo.
Seventy-one patients were randomised to receive bolus 5-FU/ FA or 5-FU/ FA + Avastin (5 mg/ kg every 2 weeks).
Randomiziranih je bilo 71 bolnikov, ki so prejeli bolus 5- FU/ FA ali 5- FU/ FA + Avastin (5 mg/ kg vsaka dva tedna).
A third group of 33 patients received bolus 5-FU/ FA + Avastin (10 mg/ kg every 2 weeks).
Tretja skupina 33- ih bolnikov je prejela bolus 5- FU/ FA + Avastin (10 mg/ kg vsaka dva tedna).
The primary endpoints of the trial were objective response rate and progression-free survival.
Dodatek 5 mg Avastina/ kg telesne mase vsake dva tedna h kemoterapiji po shemi 5- FU/ FA je povečal objektivni odgovor na zdravljenje in podaljšal preživetje brez znakov bolezni.
The addition of Avastin 5 mg/ kg every two weeks to 5-FU/ FA resulted in higher objective response rates, longer progression-free survival, and a trend in longer survival, compared with 5-FU/ FA chemotherapy alone (see Table 4).
Pokazala se je tudi težnja k daljšemu preživetju v primerjavi s preživetjem bolnikov, ki so bili zdravljeni samo s kemoterapijo po shemi 5- FU/ FA (glejte preglednico 4).
These efficacy data are consistent with the results from study AVF2107g.
Dobljeni podatki o učinkovitosti se ujemajo z izsledki študije AVF2107g.
The efficacy data from studies AVF0780g and AVF2192g investigating Avastin in combination with 5-FU/ FA-chemotherapy are summarised in Table 4.
Podatki o učinkovitosti iz študij AVF0780g in AVF2192g, ki sta proučevali zdravilo Avastin v kombinaciji s kemoterapevtsko shemo 5- FU/ FA, so povzeti v preglednici 4.
14 Table 4:
Preglednica 4.
Efficacy results for studies AVF0780g and AVF2192g
študij AVF0780g in AVF2192g
Avastina Avastinb placebo
Avastina
Avastin
Avastinb
Number of Patients Overall survival
Število bolnikov Celokupno preživetje
35 33 105
35
104
33
13.6
12, 9
95% Confidence Interval c
mediana časa (meseci) 95 -% interval zaupanja
0.52
13, 6
1.01
17, 7
0.79
15, 2
p-value
10, 35– 16, 95
0.073
13, 63– 19, 32 0, 79
0.978
razmerje ogroženosti p- vrednost Preživetje brez napredovanja bolezni
0.16
-
Median time (months)
0, 52 0, 073
9.0
1, 01 0, 978
7.2
0, 16
Hazard ratio
mediana časa (meseci) razmerje ogroženosti
0.5
5, 2
-value -
9, 0 0, 44
0.0049
7, 2 0, 69
0.0002
0, 5 0, 0002
Overall response rate
p- vrednost Odgovor na zdravljenje
16.7
-
40.0
0, 0049
24.2
0, 217
95% CI
95 -% interval zaupanja
24.4 − 57.8
24, 4−57, 8
11.7 – 42.6
p- vrednost Trajanje odgovora
9.2 - 23.9
0, 029
p-value
0, 43
0.029
0, 055
6.8
3, 8– 7, 8
9.2
5, 59– 9, 17
a
5, 88– 13, 01
25– 75 percentile (months)
25– 75 percentila (meseci) a 5 mg/ kg vsaka 2 tedna b 10 mg/ kg vsaka 2 tedna c glede na kontrolno skupino NR = ni bilo doseženo
5.5 − NR
5, 5−NR
6.1 − NR
6, 1−NR
3.8 – 7.8
NO16966
5.59 - 9.17
Slednje so bolniki prejemali na 2 tedna.
5.88 - 13.01
15 XELOX ali po shemi FOLFOX- 4.
b
V vsako od štirih skupin študije v delu II preskušanja je bilo randomiziranih približno 350 bolnikov.
5
Preglednica 5.
mg/ kg every 2 weeks.
Zdravljenje
NR = Not reached.
Začetni odmerek
15 Table 5
Shema
Treatment Regimens in Study N016966 (mCRC)
85
Schedule
mg/ m2 i. v.
FOLFOX-4
FOLFOX- 4 ali
Oxaliplatin on Day 1
oksaliplatin levkovorin
200 mg/ m IV 2 h
200 mg/ m2 i. v.
Leucovorin on Day 1 and 2
oksaliplatin 1. dan levkovorin 1. in 2. dan
5-Fluorouracil Placebo or Avastin
5- fluorouracil
400 mg/ m2 IV bolus, 600 mg/ m2 IV 22 h 5 mg/ kg IV 30-90 min
400 mg/ m2 i. v. v
5-fluorouracil IV bolus/ infusion, each on Days 1 and 2 Day 1, prior to FOLFOX-4, every 2 weeks
5- fluorouracil i. v. bolus/ infuzija,
XELOX
Avastin
Oxaliplatin
30– 90 min
Oxaliplatin on Day 1
XELOX
or XELOX+ Avastin
ali
Capecitabine
oksaliplatin kapecitabin
1000 mg/ m oral bid
1000 mg/ m2 peroralno
Capecitabine oral bid for 2 weeks (followed by 1 week off treatment)
oksaliplatin 1. dan kapecitabin peroralno dvakrat na dan 2 tedna (sledi 1- tedenski odmor)
Placebo or Avastin
XELOX+ Avastin
7.5 mg/ kg IV 30-90 min
dvakrat na dan
5-Fluorouracil:
5- fluorouracil:
IV bolus injection immediately after leucovorin
kot i. v. injekcija v bolusu neposredno po levkovorinu
In this study, there were two primary objectives: to show that XELOX was non-inferior to FOLFOX-4 and to show that Avastin in combination with FOLFOX-4 or XELOX chemotherapy was superior to chemotherapy alone.
V tej študiji sta bila primarna cilja dva: pokazati, da je shema XELOX neinferiorna shemi FOLFOX- 4, in da je zdravilo Avastin v kombinaciji s kemoterapevtskima shemama FOLFOX- 4 ali XELOX superiorno samostojni kemoterapiji.
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 and overall survival in the eligible per-protocol population.
V populaciji, ki je bila primerna glede na protokol raziskave, je bila v celokupni primerjavi glede na preživetje brez napredovanja bolezni in celokupno preživetje, dokazana neinferiornost skupin, ki so se zdravile po shemi XELOX, v primerjavi s skupinami, ki so se zdravile po shemi FOLFOX- 4.
Superiority of the Avastin-containing arms versus the chemotherapy alone arms in the overall comparison was demonstrated in terms of progression-free survival in the ITT population (Table 6)
V populaciji bolnikov, ki so jo nameravali zdraviti (ITT – intent to treat population), je bilo v celokupni primerjavi glede na preživetje brez napredovanja bolezni dokazano, da so skupine, ki so prejemale zdravilo Avastin, superiorne skupinam, ki so prejemale samo kemoterapijo (preglednica 6).
Secondary PFS analyses, based on ‘ on-treatment’ -based response assessments, confirmed the significantly superior clinical benefit for patients treated with Avastin (analyses shown in Table 6), consistent with the statistically significant benefit observed in the pooled analysis.
Sekundarne analize preživetja brez napredovanja bolezni, ki so temeljile na ocenah odgovora ob zdravljenju (′ on- treatment ′), so potrdile signifikantno superiorno klinično korist za bolnike, ki so jih zdravili z zdravilom Avastin (analiza prikazana v preglednici 6), kar je v skladu s statistično signifikantno koristjo, ki so jo opazili v združenih analizah podatkov.
16 Table 6
16 Preglednica 6.
Key efficacy results for the superiority analysis
Ključni rezultati učinkovitosti za analizo superiornosti
(ITT population, Study NO16966)
(populacija, ki so jo nameravali zdraviti; študija NO16966)
FOLFOX-4 or XELOX
FOLFOX- 4 ali XELOX
P Value
p- vrednost
+ Placebo (n=701)
+ placebo (n = 701)
Bevacizumab (n=699)
bevacizumab (n = 699)
Median PFS**
mediana preživetja brez napredovanja bolezni **
Hazard ratio (97.5% CI)a
razmerje tveganj (97, 5 -% interval zaupanja) a
Median PFS (on treatment)**
mediana preživetja brez napredovanja bolezni (ob zdravljenju) **
Hazard ratio (97.5% CI)
razmerje tveganj (97, 5 -% interval zaupanja)
0.63 (0.52-0.75)
0, 63 (0, 52– 0, 75)
Assessment)**
celokupni odgovor (ocena raziskovalca) **
Median overall survival*
mediana celokupnega preživetja *
0.89 (0.76-1.03)
0, 89 (0, 76– 1, 03)
* Overall survival analysis at clinical cut-off 31 January 2007 ** Primary analysis at clinical cut-off 31 January 2006 a relative to control arm
* Analiza celokupnega preživetja podatkov zbranih do 31. januarja 2007. ** Primarna analiza kliničnih podatkov zbranih do 31. januarja 2006. a glede na kontrolno skupino
In the FOLFOX treatment subgroup, the median PFS was 8.6 months in placebo and 9.4 months in bevacizumab treated patients, HR = 0.89, 97.5% CI = [0.73; 1.08]; p-value = 0.1871, the corresponding results in the XELOX treatment subgroup being 7.4 vs.
V podskupini, ki je prejemala zdravljenje po shemi FOLFOX, je bila mediana preživetja brez napredovanja bolezni 8, 6 meseca pri bolnikih, ki so prejemali placebo ter 9, 4 meseca pri bolnikih, ki so se zdravili z bevacizumabom; razmerje tveganj = 0, 89, 97, 5 -% interval zaupanja = [0, 73; 1, 08]; p - vrednost = 0, 1871.
9.3 months, HR = 0.77, 97.5% CI = [0.63; 0.94]; p-value = 0.0026.
V podskupini, ki je prejemala zdravljenje po shemi XELOX, je bila mediana preživetja brez napredovanja bolezni 7, 4 meseca pri bolnikih, ki so prejemali placebo ter 9, 3 meseca pri bolnikih, ki so se zdravili z bevacizumabom; razmerje tveganj = 0, 77, 97, 5 -% interval zaupanja = [0, 63; 0. 94]; p- vrednost = 0, 0026.
The median overall survival was 20.3 months in placebo and 21.2 months in bevacizumab treated patients in the FOLFOX treatment subgroup, HR=0.94, 97.5% CI = [0.75; 1.16]; p-value = 0.4937, the corresponding results in the XELOX, treatment subgroup being 19.2 vs.
Mediana celokupnega preživetja je pri bolnikih v podskupini, ki se je zdravila po shemi FOLFOX, znašala 20, 3 meseca, če so prejemali placebo in 21, 2 meseca, če so se zdravili z bevacizumabom: razmerje tveganj = 0, 94, 97, 5 -% interval zaupanja = [0, 75; 1, 16]; p- vrednost = 0, 4937.
21.4 months, HR = 0.84, 97.5% CI = [0.68; 1.04]; p-value = 0.0698.
Pri podskupini bolnikov, ki so prejemali zdravljenje po shemi XELOX, je mediana celokupnega preživetja znašala 19, 2 meseca, če so prejemali placebo in 21, 4 meseca, če so se zdravili z bevacizumabom; razmerje tveganj = 0, 84, 97, 5 -% interval zaupanja = [0, 68; 1, 04]; p- vrednost = 0, 0698.
ECOG E3200 This was a phase III randomised, active-controlled, open-label study investigating Avastin 10 mg/ kg in combination with leucovorin with 5-fluorouracil bolus and then 5-fluorouracil infusional, with IV oxaliplatin (FOLFOX-4), administered on a 2-weekly schedule in previously-treated patients (second line) with advanced colorectal cancer.
Ta zdravila so prejemali v dvotedenski shemi zdravljenja.
In the chemotherapy arms, the FOLFOX-4 regimen used the same doses and schedule as shown in Table 5 for Study NO16966.
V skupini, ki je prejemala kemoterapijo, so pri zdravljenju po shemi FOLFOX- 4 uporabljali enake odmerke in sheme, kot je prikazano v preglednici 5 za študijo NO16966.
The primary efficacy parameter of the trial was overall survival, defined as the time from randomization to death from any cause.
Primarni parameter učinkovitosti kliničnega preskušanja je bilo celokupno preživetje, opredeljeno kot čas od randomizacije do smrti zaradi katerega koli vzroka.
Eight hundred and twenty-nine patients were randomised (292 FOLFOX-4, 293 Avastin +_FOLFOX-4 and 244 Avastin monotherapy).
Dodatek zdravila Avastin
The addition of Avastin to FOLFOX-4 resulted in a statistically significant prolongation of survival.
17 k zdravljenju po shemi FOLFOX- 4 je statistično značilno podaljšal preživetje.
Statistically significant improvements in progression-free survival and objective response rate were also observed (see Table 7).
Opazili so tudi statistično značilna izboljšanja v preživetju brez napredovanja bolezni in objektivnem odgovoru na zdravljenje (glejte preglednico 7).
17 Table 7
Preglednica 7.
Efficacy Results for Study E3200
Rezultati učinkovitosti za študijo E3200
Number of Patients Overall Survival
Število bolnikov Celokupno preživetje
Median (months)
mediana (meseci)
95% confidence
95 -% interval zaupanja b
(p-value = 0.0012) Progression-Free Survival
(p- vrednost = 0, 0012) Preživetje brez napredovanja bolezni
Median (months) Hazard ratio
mediana (meseci) razmerje tveganj
(p-value < 0.0001) Objective Response Rate
(p- vrednost < 0, 0001) Objektivni odgovor na zdravljenje
Rate
delež
a 10 mg/ kg every 2 weeks b Relative to control arm
(p- vrednost < 0, 0001) a 10 mg/ kg vsaka 2 tedna b glede na kontrolno skupino
No significant difference was observed in the duration of overall survival between patients who received Avastin monotherapy compared to patients treated with FOLFOX-4.
Med bolniki, ki so prejemali zdravilo Avastin kot samostojno zdravljenje, in bolniki, ki so jih zdravili po shemi FOLFOX- 4, niso opazili pomembne razlike v trajanju celokupnega preživetja.
Progression-free survival and objective response rate were inferior in the Avastin monotherapy arm compared to the FOLFOX-4 arm.
Preživetje brez napredovanja bolezni in objektivni odgovor na zdravljenje sta bila v skupini, ki se je zdravila samo z zdravilom Avastin, inferiorna v primerjavi s skupino, ki se je zdravila po shemi FOLFOX- 4.
The benefit of Avastin re-treatment in metastatic colorectal cancer patients who were exposed to Avastin in previous therapies has not been addressed in randomized clinical trials.
Koristi ponovnega zdravljenja z zdravilom Avastin pri bolnikih z metastatskim rakom debelega črevesa in danke, ki so že bili izpostavljeni zdravilu v predhodnih zdravljenjih, v randomiziranih kliničnih preskušanjih niso proučevali.