natgillin/translations-raw huggingface dataset:
Single doses of Herceptin alone greater than 10 mg/ kg have not been administered in the clinical trials.
Enkratnih odmerkov zdravila Herceptin samega, večjih od 10 mg/ kg, v kliničnih preskušanjih niso dajali.
Antineoplastic agents, ATC code:
Farmakoterapevtska skupina: zdravila z delovanjem na novotvorbe; ATC oznaka:
L01XC03
L01XC03.
Overexpression of HER2 is observed in 20 %-30% of primary breast cancers.
Čezmerno izražanje HER2 so opazili pri 20- 30% primarnega raka dojk.
Studies indicate that patients whose tumours overexpress HER2 have a shortened disease-free survival compared to patients whose tumours do not overexpress HER2.
Študije kažejo, da imajo bolniki, katerih tumorji čezmerno izražajo HER2, krajše preživetje brez bolezni v primerjavi z bolniki, katerih tumorji ne izražajo HER2.
The extracellular domain of the receptor (ECD, p105) can be shed into the blood stream and measured in serum samples.
Ekstracelularna domena receptorja (ECD, p105) se lahko odcepi v krvni obtok in jo lahko določamo v serumskih vzorcih.
Trastuzumab has been shown, in both in vitro assays and in animals, to inhibit the proliferation of human tumour cells that overexpress HER2.
Trastuzumab je tako v in vitro študijah kot tudi pri živalih zaviral delitev človeških tumorskih celic, ki čezmerno izražajo HER2.
Additionally, trastuzumab is a potent mediator of antibody-dependent cell-mediated cytotoxicity (ADCC).
Trastuzumab je tudi močan mediator od protiteles odvisne celične citotoksičnosti (ADCC).
In vitro, trastuzumab-mediated ADCC has been shown to be preferentially exerted on HER2 overexpressing cancer cells compared with cancer cells that do not overexpress HER2.
V in vitro študijah je do s trastuzumabom posredovane ADCC preferenčno prihajalo na rakastih celicah, ki so čezmerno izražale HER2 v primerjavi s celicami, pri katerih se HER2 ne izraža.
Detection of HER2 overexpression or HER2 gene amplification Herceptin should only be used in patients whose tumours have HER2 overexpression or HER2 gene amplification as determined by an accurate and validated assay.
Ugotavljanje čezmernega izražanja HER2 ali amplifikacije gena HER2 Zdravilo Herceptin se uporablja le pri bolnikih, katerih tumorji čezmerno izražajo HER2 ali imajo amplifikacijo gena HER2, določeno s točno in validirano metodo.
HER2 overexpression should be detected using an immunohistochemistry (IHC)-based assessment of fixed tumour blocks (see 4.4).
Čezmerno izražanje HER2 ugotavljamo z imunohistokemično (IHC) metodo fiksiranih tumorskih blokov (glejte 4. 4).
HER2 gene amplification should be detected using fluorescence in situ hybridisation (FISH) or chromogenic in situ hybridisation (CISH) of fixed tumour blocks.
Amplifikacijo gena HER2 določamo z metodo fluorescenčne in situ hibridizacije (FISH) ali metodo kromogenske in situ hibridizacije (CISH) fiksiranih tumorskih blokov.
Patients are eligible for Herceptin treatment if they show strong HER2 overexpression as described by a 3+ score by IHC or a positive FISH or CISH result.
Za zdravljenje z zdravilom Herceptin so primerni bolniki, katerih rezultat čezmernega izražanja HER2 po IHC metodi znaša 3+ ali bolniki, katerih rezultat metod FISH ali CISH je pozitiven.
The recommended scoring system to evaluate the IHC staining patterns is as follows:
Priporočen način vrednotenja rezultatov obarvanja preparatov po IHC metodi:
Staining Intensity Score
Rezultat intenzitete obarvanja
Staining pattern
Izgled preparata po barvanju
HER2 Overexpression Assessment
Ocena čezmernega izražanja HER2
No staining is observed or membrane staining is observed in < 10% of the tumour cells
Obarvanje ni prisotno ali pa so obarvane membrane pri < 10% vseh tumorskih celic v preparatu.
A faint/ barely perceptible membrane staining is detected in > 10% of the tumour cells.
Bledo, komaj zaznavno obarvanje membrane je prisotno pri > 10% tumorskih celic.
A weak to moderate complete membrane staining is detected in > 10% of the tumour cells.
Šibko do srednje močno obarvane celotne membrane pri > 10% tumorskih celic.
Weak to moderate overexpression
Šibko do srednje čezmerno izražanje.
A moderate to strong complete membrane staining is detected in > 10% of the tumour cells.
Srednje do močno obarvane celotne membrane pri > 10% tumorskih celic.
Moderate to strong overexpression
Srednje do močno čezmerno izražanje.
15 In general, FISH is considered positive if the ratio of the HER2 gene copy number per tumour cell to the chromosome 17 copy number is greater than or equal to 2, or if there are more than 4 copies of the HER2 gene per tumour cell if no chromosome 17 control is used.
V splošnem velja, da je rezultat metode FISH pozitiven, če je razmerje med številom kopij gena HER2 na tumorsko celico in številom kopij kromosoma 17 večje ali enako 2, ali če je število kopij gena HER2 na tumorsko celico večje od 4, če ne uporabimo kontrole s kromosomom 17.
In general, CISH is considered positive if there are more than 5 copies of the HER2 gene per nucleus in greater than 50% of tumour cells.
V splošnem velja, da je rezultat metode CISH pozitiven, če obstaja več kot 5 kopij gena HER2 na jedro v več kot 50% tumorskih celic.
For full instructions on assay performance and interpretation please refer to the package inserts of validated FISH and CISH assays.
Za popolna navodila o učinkovitosti metod in interpretaciji rezultatov prosimo glejte navodila za uporabo validiranih metod FISH in CISH.
Official recommendations on HER2 testing may also apply.
Veljajo tudi uradna priporočila za HER2 testiranje.
For any other method that may be used for the assessment of HER2 protein or gene expression, the analyses should only be performed by laboratories that provide adequate state-of-the-art performance of validated methods.
16 Za katerokoli drugo metodo, ki se lahko uporablja za oceno ekspresije HER2 proteina ali gena, lahko analize izvajajo le laboratoriji, ki uporabljajo ustrezne sodobne validirane metode.
Clinical Data Herceptin has been used in clinical trials as monotherapy for patients with metastatic breast cancer who have tumours that overexpress HER2 and who have failed one or more chemotherapy regimens for their metastatic disease (Herceptin alone).
Klinični podatki Zdravilo Herceptin so v kliničnih preskušanjih uporabljali kot monoterapijo pri bolnikih z metastatsko obliko raka dojk, katerih tumorji čezmerno izražajo HER2 in pri katerih je prišlo do napredovanja bolezni po eni ali več kemoterapevtskih zdravljenjih njihove metastatske bolezni (le zdravilo Herceptin).
Patients who had previously received anthracycline-based adjuvant chemotherapy were treated with paclitaxel (175 mg/ m2 infused over 3 hours) with or without Herceptin.
Bolnike, ki so predhodno prejemali adjuvantno kemoterapijo na osnovi antraciklinov, so zdravili s paklitakselom (175 mg/ m2 infundirano v 3 urah) samim ali skupaj z zdravilom Herceptin.
In the pivotal trial of docetaxel (100 mg/ m2 infused over 1 hour) with or without Herceptin, 60% of the patients had received prior anthracycline-based adjuvant chemotherapy.
V ključnem preskušanju docetaksela (100 mg/ m2 infudirano v 1 uri) z zdravilom Herceptin ali brez, je 60% bolnikov predhodno prejelo adjuvantno kemoterapijo na osnovi antraciklinov.
However, Herceptin plus docetaxel was efficacious in patients whether or not they had received prior adjuvant anthracyclines.
Zdravilo Herceptin pa je bilo skupaj z docetakselom učinkovito neglede na to, ali so bolniki prej prejeli adjuvantno terapijo z antraciklini ali ne.
The test method for HER2 overexpression used to determine eligibility of patients in the pivotal Herceptin monotherapy and Herceptin plus paclitaxel clinical trials employed immunohistochemical staining for HER2 of fixed material from breast tumours using the murine monoclonal antibodies CB11 and 4D5.
Testna metoda za določanje čezmerno izraženega HER2, s čimer ugotovijo primernost bolnika, ki so jo uporabili v ključnih kliničnih preskušanjih monoterapije zdravila Herceptin in zdravila Herceptin z docetakselom, je osnovana na imunohistokemičnem barvanju HER2 v fiksiranih preparatih tumorjev dojk, po uporabi murinih monoklonskih protiteles CB11 in 4D5.
These tissues were fixed in formalin or Bouin’ s fixative.
Tkiva so bila fiksirana s formalinom ali v Bouinsovem fiksativu.
This investigative clinical trial assay performed in a central laboratory utilised a 0 to 3+ scale.
Preiskovalno metodo so za potrebe kliničnega preskušanja izvajali v centralnem laboratoriju in za vrednotenje rezultatov uporabili lestvico od 0 do 3+.
Greater than 70% of patients enrolled exhibited 3+ overexpression.
Več kot 70% vključenih bolnikov je izkazovalo čezmerno izražanje stopnje 3+.
The main test method used to determine HER2 positivity in the pivotal trial of docetaxel, with or without Herceptin, was immunohistochemistry.
Glavna preskusna metoda, ki so jo uporabili za določitev HER2 pozitivnosti v ključnem preskušanju docetaksela skupaj z zdravilom Herceptin ali brez, je bila imunohistokemija.
A minority of patients were tested using fluorescence in-situ hybridisation (FISH).
Manjši del bolnikov so testirali z metodo fluorescenčne hibridizacije in- situ (FISH).
In this trial, 87% of patients entered had disease that was IHC3+, and 95% of patients entered had disease that was IHC3+ and/ or FISH-positive.
V tem preskušanju je 87% vključenih bolnikov imelo bolezen, ki je bila IHC3+, 95% vključenih bolnikov pa je imelo bolezen, ki je bila IHC3+ in/ ali FISH- pozitivna.
Weekly dosing in MBC
Tedensko odmerjanje pri metastatskem raku dojk
The efficacy results from the monotherapy and combination therapy studies are summarised in the following table:
Naslednja preglednica navaja rezultate učinkovitosti monoterapije in kombiniranega zdravljenja:
16 Parameter
17 Parameter
Monotherapy
Zdravilo
Combination Therapy
docetaksel3
Herceptin Paclitaxel2 Herceptin Docetaxel3 plus plus 2 paclitaxel docetaxel3
Herceptin in
N=172
n = 77
N=68 N=77 N=92 N=94
docetaksel3
Response rate (95%CI)
delež odgovora (95 -
(13 - 25)
34%
(36 - 61) (9 - 27) (50-71)
% interval zaupanja)
(25-45)
(9−27)
Median duration of response (months)
mediana časa odgovora (meseci)
8.3 4.6 11.7
11, 7 (9, 3−15, 0)
(95%CI)
(5, 6−10, 3)
(5.6-10.3)
(7, 3−8, 8)
(7.3-8.8) (3.7-7.4) (9.3 – 15.0)
(3, 7−7, 4)
(4.6-7.6)
(4, 6−7, 6)
Median TTP (months) (95%CI)
mediana TTP
(2.6-3.5)
(2, 0−4, 4)
(6.2-12.0) (2.0-4.4) (9.2-13.5)
(9, 2−13, 5)
(5.4-7.2)
(5, 4−7, 2)
Median Survival (months) (95%CI)
mediana preživetja
16.4
17, 9
24.8 17.9 31.2
31, 2
22.74
22, 74
(12.3-ne)
(12, 3−ne)
(18.6-33.7) (11.2-23.8) (27.3-40.8) (19.1-30.8)
(18, 6−33, 7) (11, 2−23, 8) (27, 3−40, 8) (19, 1−30, 8)
TTP = time to progression; "ne" indicates that it could not be estimated or it was not yet reached.
TTP = čas do napredovanja bolezni; "ne" – ni bilo možno oceniti ali pa še ni bilo doseženo.
Study H0649g:
Študija H0649g:
IHC3+ patient subset 2.
IHC3+ podskupina bolnikov 2.
Study H0648g:
Študija H0648g:
IHC3+ patient subset 3.
IHC3+ podskupina bolnikov 3.
Full analysis set (intent-to-treat)
Študija M77001: celotna skupina bolnikov (z namenom zdraviti, intent- to- treat)
Herceptin has been studied in combination with anastrozole for first line treatment of metastatic breast cancer in HER2 overexpressing, hormone-receptor (i. e. estrogen-receptor (ER) and/ or progesterone- receptor (PR)) positive postmenopausal patients.
Zdravilo Herceptin so proučevali v kombinaciji z anastrozolom v prvi liniji zdravljenja metastatskega raka dojk pri bolnicah v postmenopavzi s čezmerno izraženim HER2 in pozitivnimi hormonskimi receptorji (estrogenski ali progesteronski receptorji ali oboje).
Progression free survival was doubled in the Herceptin plus anastrozole arm compared to anastrozole (4.8 months versus 2.4 months).
Preživetje brez napredovanja bolezni je bilo v skupini, ki je prejemala zdravilo Herceptin in anastrozol, dvakrat daljše (4, 8 meseca) kot v skupini, ki je jemala le anastrozol (2, 4 meseca).
For the other parameters the improvements seen for the combination were for overall response (16.5% versus 6.7%); clinical benefit rate (42.7% versus 27.9%); time to progression (4.8 months versus 2.4 months).
Pri drugih parametrih so bila izboljšanja pri kombinaciji vidna pri celokupnem odgovoru (16, 5% v primerjavi s 6, 7%), deležu klinične koristi (42, 7% v primerjavi s 27, 9%) in času do napredovanja bolezni (4, 8 mesece v primerjavi z 2, 4 meseca).
The median overall survival was extended by 4.6 months for patients in the combination arm.
Mediana celokupnega preživetja je bila v skupini, ki je jemala kombinacijo zdravil, daljša za 4, 6 meseca.
The difference was not statistically significant, however more than half of the patients in the anastrozole alone arm crossed over to a Herceptin containing regimen after progression of disease.
Razlika ni bila statistično značilna, vendar pa je več kot polovica bolnikov iz skupine, ki je jemala le anastrozol po napredovanju bolezni prešla na shemo, ki je vsebovala zdravilo Herceptin.
3-weekly dosing in MBC
Odmerjanje enkrat na tri tedne pri metastatskem raku dojk
The efficacy results from the non-comparative monotherapy and combination therapy studies are summarised in the following table:
Naslednja preglednica navaja rezultate učinkovitosti monoterapije in kombiniranega zdravljenja iz študij brez primerjalne skupine:
17 Parameter
18 Parameter
Monotherapy
monoterapija
Combination Therapy
kombinirano zdravljenje
Herceptin2
Zdravilo Zdravilo
Herceptin plus paclitaxel3
Zdravilo Herceptin
Herceptin plus Docetaxel4
Zdravilo Herceptin in
N=105
Herceptin1 n = 105
N=72
Herceptin2 n = 72
N=32
in paklitaksel3 n = 32
N=110
docetaksel4 n = 110
(15 - 35)
(15- 35)
(14 - 43)
(14- 43)
Median duration of response (months)
mediana časa
10.5 (1.8-21)
10, 5
13.4
13, 4
Study WO16229: loading dose 8 mg/ kg, followed by 6 mg/ kg 3 weekly schedule 2.
Študija WO16229: uvajalni odmerek 8 mg/ kg, sledil je odmerek 6 mg/ kg po 3- tedenskem režimu 2.
Study MO16982: loading dose 6mg/ kg weekly x 3; followed by 6mg/ kg 3-weekly schedule 3.
Študija MO16982: uvajalni odmerek 6 mg/ kg tedensko 3 tedne; sledil je odmerek 6 mg/ kg po 3 - tedenskem režimu 3.
MO16419EBC
Zgodnji rak dojk
Early breast cancer in the HERA trial was limited to operable, primary, invasive adenocarcinoma of the breast, with axillary nodes positive or axillary nodes negative if tumours at least 1 cm in diameter.
Zgodnji rak dojk v kliničnem preskušanju HERA je bil omejen na operabilni, primarni, invazivni adenokarcinom dojk, s pozitivnimi aksilarnimi bezgavkami ali negativnimi aksilarnimi bezgavkami, če so tumorji v premeru znašali vsaj 1 cm.
In the adjuvant setting, Herceptin was investigated in a multicentre, randomised, trial (HERA) designed to compare one year of three-weekly Herceptin treatment versus observation in patients with HER2 positive early breast cancer following surgery, established chemotherapy and radiotherapy (if applicable).
Pri adjuvantnem zdravljenju so zdravilo Herceptin proučevali v multicentričnem, randomiziranem preskušanju (HERA), ki je bilo zasnovano za primerjavo enoletnega zdravljenja z zdravilom Herceptin z odmerjanjem na 3 tedne in opazovanja bolnikov z zgodnjo obliko HER2 pozitivnega raka dojk po operaciji, standardni kemoterapiji in radioterapiji (če je primerno).
Patients assigned to receive Herceptin were given an initial loading dose of 8 mg/ kg, followed by 6 mg/ kg every three weeks for one year.
Bolniki, ki so bili določeni za prejemanje zdravila Herceptin, so prejeli začetni uvajalni odmerek 8 mg/ kg telesne mase, nato pa eno leto 6 mg/ kg telesne mase vsak tretji teden.
The efficacy results from the Hera trial are summarized in the following table:
19 Rezultati učinkovitosti kliničnega preskušanja HERA so povzeti v sledeči preglednici:
Parameter Disease-free survival
Parameter Preživetje brez bolezni
Observation N=1693
Opazovanje n = 1. 693
Herceptin 1 Year N = 1693
Zdravilo Herceptin 1 leto n = 1. 693
P-value vs Observation
p- vrednost v primerjavi z opazovanjem
Hazard Ratio vs Observation
Razmerje tveganja v primerjavi z Opazovanjem
- No. patients with event - No. patients without event Recurrence-free survival
- število bolnikov z dogodkom
- No. patients with event - No. patients without event Distant disease-free survival
Preživetje brez ponovitve bolezni -
- No. patients with event - No. patients without event
Preživetje brez pojava oddaljenih metastaz -
For the primary endpoint, DFS, the hazard ratio translates into an absolute benefit, in terms of a 2-year disease-free survival rate, of 7.6 percentage points (85.8% vs 78.2%) in favour of the Herceptin arm.
Za primarni cilj, preživetje brez bolezni, razmerje tveganja kaže absolutno korist v smislu 2- letnega preživetja brez bolezni 7, 6 odstotnih točk (85, 8% v primerjavi z 78, 2%) v korist skupine, ki je prejemala zdravilo Herceptin.
Immunogenicity Nine hundred and three patients treated with Herceptin, alone or in combination with chemotherapy, have been evaluated for antibody production.
Imunogenost Na tvorbo protiteles so bili testirani 903 bolniki zdravljeni z zdravilom Herceptin samim ali v kombinaciji s kemoterapijo.
Human anti-trastuzumab antibodies were detected in one patient, who had no allergic manifestations.
Humana protitelesa proti trastuzumabu so odkrili le pri enem bolniku, ki ni imel izražene alergije.
19 Sites of progression After Herceptin and paclitaxel therapy for metastatic breast cancer in patients in the pivotal trial the following sites of disease progression were found:
Mesta napredovanja bolezni V ključnem preskušanju so po zdravljenju metastatske oblike raka dojk z zdravilom Herceptin in paklitakselom opazili naslednja mesta napredovanja bolezni:
Site*
Mesto *
Herceptin plus paclitaxel (N=87)%
Herceptin in paklitaksel (n = 87)
paclitaxel (N=92)%
= 92)%
Any site
70, 1
70.1
95, 7
95.7
trebuh
Abdomen Bone Chest Liver Lung Dist.
kosti prsni koš jetra pljuča distalni limfni vozli mediastinum CŽS drugo
Node Mediastinum CNS Other
17, 2 5, 7 21, 8 16, 1 3, 4 4, 6 12, 6 4, 6
0 17.2 5.7 21.8 16.1 3.4 4.6 12.6 4.6
16, 3 13, 0 45, 7 18, 5 6, 5 2, 2 6, 5 9, 8
0 16.3 13.0 45.7 18.5 6.5 2.2 6.5 9.8
0, 986 0, 250 0, 004 0, 915 0, 643 0, 667 0, 377 0, 410
- 0.986 0.250 0.004 0.915 0.643 0.667 0.377 0.410
* Bolniki so lahko imeli več mest napredovanja.
*Patients may have had multiple sites of disease progression
Pogostost napredovanja v jetrih je bila signifikantno zmanjšana pri bolnikih, zdravljenih s kombinacijo
The frequency of progression in the liver was significantly reduced in patients treated with the combination of Herceptin and paclitaxel.
20 zdravila Herceptin in paklitaksela.
More patients treated with Herceptin and paclitaxel progressed in the central nervous system than those treated with paclitaxel alone.
Progresija v osrednjem živčnem sistemu je bila pri bolnikih, zdravljenih z zdravilom Herceptin in paklitakselom pogostejša kot pri tistih, ki so prejemali le paklitaksel.
The pharmacokinetics of trastuzumab have been studied in patients with metastatic breast cancer and early breast cancer.
Farmakokinetiko trastuzumaba so proučevali pri bolnikih z metastatsko in zgodnjo obliko raka dojk.
Short duration intravenous infusions of 10, 50, 100, 250, and 500 mg trastuzumab once weekly in patients demonstrated dose-dependent pharmacokinetics.
S kratkimi intravenskimi infuzijami po 10, 50, 100, 250 in 500 mg trastuzumaba enkrat tedensko, so ugotovili, da je farmakokinetika odvisna od odmerka.
Drug interaction studies have not been performed with Herceptin.
Raziskav medsebojnega delovanja zdravila Herceptin z drugimi zdravili niso opravili.
Half-life The half-life is approximately 28.5 days (95% confidence interval, 25.5 – 32.8 days).
Razpolovni čas Razpolovni čas je približno 28, 5 dni (95 -% interval zaupanja, 25, 5– 32, 8 dni).
The washout period is up to 24 weeks (95% confidence interval, 18-24 weeks)
Doba izpiranja je do 24 tednov (95 -% interval zaupanja, 18- 24 tednov).
Steady State Concentration Steady state pharmacokinetics should be reached by approximately 20 weeks (95% confidence interval, 18 – 24 weeks).
Stanje dinamičnega ravnovesja Stanje dinamičnega ravnovesja dosežemo po približno 20 tednih (95 -% interval zaupanja, 18- 24 tednov).
In a population pharmacokinetic assessment of Phase I, II and III clinical trials in metastatic breast cancer, the estimated mean AUC was 578 mg day/ L and the estimated mean peak and trough concentrations were 110 mg/ L and 66 mg/ L, respectively.
V populacijski farmakokinetični oceni faz I, II in III kliničnih preskušanj pri metastatskem raku dojk, je bila ocenjena srednja AUC 578 mg. dan/ l, ocenjene srednje maksimalne koncentracije 110 mg/ l, srednje minimalne koncentracije pa 66 mg/ l.
In patients with early breast cancer administered Herceptin at a loading dose of 8 mg/ kg followed every three weeks by 6 mg/ kg, steady state trough concentrations of 63 mg/ L were achieved by cycle 13 (week 37).
Pri bolnikih z zgodnjim rakom dojk, ki so prejeli uvajalni odmerek 8 mg/ kg telesne mase zdravila Herceptin, nato pa 6 mg/ kg telesne mase na tri tedne, je bila minimalna koncentracija v stanju dinamičnega ravnovesja 63 mg/ l dosežena do 13 cikla (37 teden).
The concentrations were comparable to those reported previously in patients with metastatic breast cancer.
Koncentracije so bile primerljive s tistimi, o katerih so prej poročali pri bolnikih z metastatskim rakom dojk.
Clearance Clearance decreased with increased dose level.
Očistek Očistek se je s povečanjem odmerka zmanjšal.
In clinical trials where a loading dose of 4 mg/ kg trastuzumab followed by a subsequent weekly dose of 2 mg/ kg was used, the mean clearance was 0.225L/ day.
V kliničnih preskušanjih, kjer je začetni odmerek znašal 4 mg/ kg trastuzumaba, nato pa so mu sledili tedenski odmerki 2 mg/ kg, je bil srednji očistek 0, 225 l/ dan.
The effects of patient characteristics (such as age or serum creatinine) on the disposition of trastuzumab have been evaluated.
Proučevali so tudi vpliv karakteristik bolnikov (kot sta starost ali serumski kreatinin) na razpoložljivost trastuzumaba.
The data suggest that the disposition of trastuzumab is not altered in
Podatki nakazujejo, da razpoložljivost trastuzumaba ni spremenjena v nobeni od omenjenih skupin bolnikov (glejte poglavje 4. 2), vendar je treba upoštevati, da študije niso specifično načrtovane za proučevanje vpliva odpovedi ledvic na farmakokinetiko.
Volume of Distribution In all clinical studies, volume of distribution approximated serum volume, 2.95 L.
Volumen porazdelitve V vseh kliničnih študijah je volumen porazdelitve približno ustrezal serumskemu volumnu 2, 95 l.
Circulating Shed Antigen Detectable concentrations of the circulating extracellular domain of the HER2 receptor (shed antigen) are found in the serum of some patients with HER2 overexpressing breast cancers.
Krožeči odcepljeni antigen V serumu nekaterih bolnikov z rakom dojk in čezmerno izraženim HER2 so našli krožeče ekstracelularne domene receptorja HER2 (odcepljeni antigen) v merljivih koncentracijah.
Determination of shed antigen in baseline serum samples revealed that 64% (286/ 447) of patients had detectable shed antigen, which ranged as high as 1880 ng/ ml (median = 11 ng/ ml).
Določitev odcepljenega antigena v serumskih vzorcih v stanju ravnotežja je pokazala, da ima 64% (286/ 447) bolnikov merljiv odcepljen antigen, katerega koncentracija je znašala do 1. 880 ng/ ml (srednja vrednost 11 ng/ ml).
Patients with higher baseline shed antigen levels were more likely to have lower serum trough concentrations of trastuzumab.
Pri bolnikih z visoko koncentracijo odcepljenega antigena v stanju dinamičnega ravnovesja so bile pogostejše nižje serumske koncentracije trastuzumaba.
However, with weekly dosing, most patients with elevated shed antigen levels achieved target serum concentrations of trastuzumab by week 6 and no significant relationship has been observed between baseline shed antigen and clinical response.
Med koncentracijami odcepljenega antigena v stanju ravnotežja in kliničnim odzivom ni bilo signifikantnih povezav.