natgillin/translations-raw huggingface dataset:
Therefore, clinical drug-drug interactions are unlikely to occur as a result of crizotinib-mediated inhibition of the hepatic or renal uptake of medicinal products that are substrates for these transporters.
Stoga nisu vjerojatne kliničke interakcije s drugim lijekovima kao posljedica krizotinibom posredovane inhibicije jetrenih ili bubrežnih transportera unosa lijekova koji su njihovi supstrati.
In rat and dog repeat-dose toxicity studies up to 3-month duration, the primary target organ effects were related to the gastrointestinal (emesis, faecal changes, congestion), haematopoietic (bone marrow hypocellularity), cardiovascular (mixed ion channel blocker, decreased heart rate and blood pressure, increased LVEDP, QRS and PR intervals, and decreased myocardial contractility), or reproductive (testicular pachytene spermatocyte degeneration, single-cell necrosis of ovarian follicles) systems.
U ispitivanjima toksičnosti ponovljenih doza na štakorima i psima u trajanju do 3 mjeseca, primarni učinci na ciljnim organima zabilježeni su u probavnom (povraćanje, promjene fecesa, kongestija), hematopoetskom (hipocelularnost koštane srži), kardiovaskularnom (blokada različitih ionskih kanala, usporena srčana frekvencija i snižen krvni tlak, povišen LVEDP (krajnji dijastolički tlak lijeve pretklijetke), produljen QRS- i PR-interval te smanjena kontraktilnost miokarda) i reproduktivnom sustavu (pahitenska degeneracija spermatocita u testisima, nekroza pojedinačnih stanica folikula u jajnicima).
NR (45.8, NR)
ND (45,8; ND)
Complete blood counts including differential white blood cell counts should be monitored as clinically indicated, with more frequent repeat testing if Grade 3 or 4 abnormalities are observed, or if fever or infection occurs (see section 4.2).
Potrebno je kontrolirati kompletnu krvnu sliku, uključujući i diferencijalni broj bijelih krvnih stanica, sukladno kliničkoj indikaciji, a pretrage treba češće ponavljati ako se uoče odstupanja stupnja 3 ili 4 ili ako nastupi vrućica ili infekcija (vidjeti dio 4.2).
Carcinogenicity studies with crizotinib have not been performed.
Nisu provedena ispitivanja kancerogenosti krizotiniba.
Patient-reported symptoms and global QOL were collected using the EORTC QLQ-C30 and its lung cancer module (EORTC QLQ-LC13).
Simptomi koje su prijavili bolesnici i globalna kvaliteta života prikupljeni su upitnikom EORTC QLQ-C30 i njegovim modulom za rak pluća (EORTC QLQ-LC13).
• Cisapride, used to treat stomach problems.
• cisapridom - koristi se za liječenje želučanih tegoba.
If you have any questions about how XALKORI works or why this medicine has been prescribed for you, ask your doctor.
Ako imate pitanja o tome kako XALKORI djeluje ili zašto
In vitro studies showed that crizotinib is a weak inhibitor of UGT1A1 and UGT2B7 (see section 4.5).
In vitro ispitivanja pokazala su da je krizotinib slabi inhibitor UGT1A1 i UGT2B7 (vidjeti dio 4.5).
Chemotherapy N=171
kemoterapija N=171
If QTc increases by greater than or equal to 60 msec from baseline but QTc is <500 msec, crizotinib should be withheld and cardiologist advice should be sought.
Ako se QTc poveća za 60 msek ili više u odnosu na početne vrijednosti, ali je QTc < 500 msek, potrebno je privremeno prekinuti primjenu krizotiniba i potražiti savjet kardiologa.
Crizotinib significantly prolonged progression-free survival (PFS), the primary objective of the study, compared to chemotherapy as assessed by IRR.
Krizotinib je značajno produžio preživljenje bez progresije bolesti (engl. progression-free survival, PFS), što je bio primarni cilj ispitivanja, u usporedbi s kemoterapijom koja je procijenjena IRR-om.
k. Oesophagitis (Oesophagitis, Oesophageal ulcer).
k. Ezofagitis (ezofagitis, ezofagealni ulkus).
Patients with pulmonary symptoms indicative of ILD/pneumonitis should be monitored.
Potrebno je nadzirati bolesnike s plućnim simptomima koji ukazuju na IBP/pneumonitis.
In clinical studies with crizotinib, events of gastrointestinal perforations were reported.
U kliničkim ispitivanjima s krizotinibom prijavljeni su slučajevi gastrointestinalnih perforacija.
Patient-reported symptoms and global QOL were collected using the EORTC QLQ-C30 and its lung cancer module (EORTC QLQ-LC13) at baseline (Day 1 Cycle 1) and Day 1 of each subsequent treatment cycle.
Simptomi koje su prijavili bolesnici i globalna kvaliteta života prikupljeni su upitnikom EORTC QLQ-C30 i njegovim modulom za rak pluća (EORTC QLQ-LC13) na početku ispitivanja (1. dan 1. ciklusa) i 1. dana svakog naknadnog ciklusa liječenja.
Grapefruit or grapefruit juice may also increase plasma concentrations of crizotinib and should be avoided (see sections 4.2 and 4.4).
Grejp i sok od grejpa također mogu povećati koncentracije krizotiniba u plazmi te ih treba izbjegavati (vidjeti dijelove 4.2 i 4.4).
Patients randomised to chemotherapy could cross over to receive crizotinib upon RECIST-defined disease progression confirmed by independent radiology review (IRR).
Bolesnici randomizirani u kemoterapijsku skupinu mogli su preći u skupinu krizotiniba nakon što je progresija bolesti definirana RECIST-om potvrđena neovisnom radiološkom procjenom (engl. independent radiology review, IRR).
The absolute bioavailability of crizotinib was determined to be 43% following the administration of a single 250 mg oral dose.
Utvrđena je apsolutna bioraspoloživost krizotiniba od 43% nakon primjene jedne peroralne doze od 250 mg.
MARKETING AUTHORISATION NUMBER(S) XALKORI 200 mg hard capsules EU/1/12/793/001
XALKORI 200 mg tvrde kapsule EU/1/12/793/001
After a single 250 mg dose in subjects with severe renal impairment (CLcr <30 mL/min) not requiring peritoneal dialysis or haemodialysis, crizotinib AUCinf and Cmax increased by 79% and 34%, respectively, compared to those with normal renal function.
Nakon pojedinačne doze od 250 mg u bolesnika sa teškim oštećenjem bubrega (CLcr <30 mL/min) koje ne zahtjeva peritonealnu dijalizu ili hemodijalizu, AUCinf i Cmax je očekivano povećana 79% i 34%, u usporedbi sa bolesnicima normalne bubrežne funkcije.
• Efavirenz, raltegravir, used to treat HIV infection.
• efavirenzom, raltegravirom - koriste se za liječenje infekcije HIV-om.
If patients have severe renal impairment not requiring peritoneal dialysis or haemodialysis, the dose of crizotinib should be adjusted (see sections 4.2 and 5.2).
Ako bolesnici imaju teško oštećenje funkcije bubrega koje ne zahtjeva peritonealnu dijalizu ili hemodijalizu, doza krizotiniba se treba prilagoditi (vidjeti dijelove 4.2 i 5.2).
Patients could continue crizotinib treatment beyond the time of Response Evaluation Criteria in Solid Tumours (RECIST)-defined disease progression at the discretion of the investigator if the patient was still experiencing clinical benefit.
Bolesnici su mogli nastaviti liječenje krizotinibom nakon vremena progresije bolesti definirane prema Kriterijima procjene odgovora kod solidnih tumora (RECIST), prema odluci ispitivača, ako je bolesnik još uvijek imao kliničku korist.
There were reports of fatal cases of gastrointestinal perforation during post-marketing use of crizotinib (see section 4.8).
Bilo je izvješća o smrtnim slučajevima gastrointestinalne perforacije tijekom uporabe krizotiniba nakon stavljanja u promet (vidjeti dio 4.8).
The most frequent adverse reactions (≥3%, all-causality frequency) associated with dosing interruptions were neutropenia (11%), elevated transaminases (7%), vomiting (5%), and nausea (4%).
Najčešće nuspojave (≥3%, učestalost svih uzroka) povezane s prekidom primjene lijeka bile su neutropenija (11%), povišene transaminaze (7%), povraćanje (5%) i mučnina (4%).
Coadministration of crizotinib with strong CYP3A inhibitors is expected to increase crizotinib plasma concentrations.
Očekuje se da će istodobna primjena krizotiniba sa snažnim inhibitorima CYP3A povisiti koncentraciju krizotiniba u plazmi.
In vitro studies indicated that crizotinib is a weak inhibitor of uridine diphosphate glucuronosyltransferase (UGT)1A1 and UGT2B7.
In vitro ispitivanja pokazuju da je krizotinib slabi inhibitor uridin difosfat glukuronoziltransferaze (UGT)1A1 i UGT2B7.
o. Blood creatinine increased (blood creatinine increased, creatinine renal clearance decreased).
Povišeni kreatinin u krvi (povišeni kreatinin u krvi, smanjen bubrežni klirens kreatinina).
Efficacy data from Study 1007 are summarised in Table 5, and the Kaplan-Meier curves for PFS and OS are shown in Figure 3 and 4, respectively.
Podaci o djelotvornosti u Ispitivanju 1007 navedeni su u Tablici 5, a Kaplan-Meierove krivulje PFS-a i OS-a prikazane su u Slici 3, odnosno 4.
Coadministration with medicinal products that are substrates of transporters
Istodobna primjena s lijekovima koji su supstrati transportnih proteina
Chemotherapy N=174
kemoterapija N=174
Crizotinib is also an inhibitor of the Hepatocyte Growth Factor Receptor (HGFR, c-Met) RTK, ROS1 (c-ros) and Recepteur d'Origine Nantais (RON) RTK.
Krizotinib je također inhibitor receptorske tirozin kinaze hepatocitnog faktora rasta (engl. hepatocyte growth factor receptor, HGFR, c-Met), ROS1 (c-ros) i RON (franc.
One hundred forty-four (84%) patients in the chemotherapy arm received subsequent crizotinib treatment.
Sto četrdeset i četiri (84%) bolesnika u skupini koja je primala kemoterapiju primilo je nakon toga liječenje krizotinibom.
The full analysis population included 343 patients with ALK-positive advanced NSCLC as identified by Fluorescence In Situ Hybridization (FISH) prior to randomisation: 172 patients were randomised to crizotinib and 171 patients were randomised to chemotherapy (pemetrexed + carboplatin or cisplatin; up to 6 cycles of treatment).
Potpuna analiza populacije uključivala je 343 bolesnika s ALK-pozitivnim uznapredovalim NSCLCom, kako je utvrđeno testom fluorescentne in situ hibridizacije (FISH) prije randomizacije: 172 bolesnika bila su randomizirana u skupinu krizotiniba, a 171 bolesnik u kemoterapijsku skupinu (pemetreksed + karboplatin ili cisplatin; do 6 ciklusa liječenja).
In Study 1014, the median duration of study treatment was 47 weeks for patients in the crizotinib arm (N=171); the median duration of treatment was 23 weeks for patients who crossed over from the chemotherapy arm to receive crizotinib treatment (N=109).
U ispitivanju 1014, medijan trajanja ispitivanja liječenja bio je 47 tjedna za bolesnike u skupini koja je primala krizotinib (N=171); medijan trajanja liječenja bio je 23 tjedna za bolesnike koji su prešli iz skupine koja je primala kemoterapiju u skupinu koja se liječila krizotinibom (N=109).
According to an independent review committee (IRC) assessment of patients with ALK-positive NSCLC (N=1669), 20 (1.2%) patients had ILD/pneumonitis, including 10 (<1%) patients with fatal cases.
Prema ocjeni Nezavisnog odbora za procjenu bolesnika s ALK-pozitivnim NSCLC-om (N=1669), 20 (1,2%) bolesnika je imalo IBP/pneumonitis, uključujući 10 (<1%) bolesnika sa smrtnim slučajem.
• First dose reduction: XALKORI 200 mg taken orally twice daily
• prvo smanjenje doze: XALKORI 200 mg, primijenjen peroralno dvaput na dan
For ALK-positive NSCLC patients in Studies 1001 (N=154) and 1005 (N=1063), the median duration of treatment was 57 and 45 weeks, respectively.
Za bolesnike s ALK-pozitivnim NSCLC-om u ispitivanjima 1001 (N=154) i 1005 (N=1063), medijan trajanja liječenja bio je 57 odnosno 45 tjedana.
• The recommended dose is one capsule of 250 mg taken orally twice daily (total amount
• Preporučena doza je jedna kapsula od 250 mg, koja se uzima kroz usta dvaput na dan (ukupna količina 500 mg na dan).
For ROS1-positive NSCLC patients in Study 1001 (N=53), the median duration of treatment was 101 weeks.
Za bolesnike s ROS1-pozitivnim NSCLC-om u ispitivanju 1001 (N=53), medijan trajanja liječenja iznosio je 101 tjedan.
e. For patients treated with 250 mg once daily or whose dose was reduced to 250 mg once daily, discontinue during evaluation.
U bolesnika liječenih dozom od 250 mg jedanput na dan ili onih kojima je doza smanjena na 250 mg jedanput na dan, obustaviti primjenu tijekom procjene.
The recommended dose schedule of XALKORI is 250 mg twice daily (500 mg daily) taken continuously.
Preporučena doza lijeka XALKORI je 250 mg dvaput na dan (ukupno 500 mg na dan), a uzima se kontinuirano.
Crizotinib demonstrated antitumour efficacy, including marked cytoreductive antitumour activity, in mice bearing tumour xenografts that expressed ALK fusion proteins.
Krizotinib je dokazao djelotvornost protiv tumora, uključujući izraženo citoreduktivno antitumorsko djelovanje, u miševa s tumorskim ksenograftima koji su izražavali proteine ALK-inačica nastalih fuzijom.
Agents that may increase crizotinib plasma concentrations
Lijekovi koji mogu povisiti koncentraciju krizotiniba u plazmi
The most common adverse reactions (≥25%) in patients with either ALK-positive or ROS1-positive NSCLC were vision disorder, nausea, diarrhoea, vomiting, oedema, constipation, elevated transaminases, fatigue, decreased appetite, dizziness, and neuropathy.
Najčešće nuspojave (≥ 25%) u bolesnika bilo s ALK-pozitivnim ili ROS1-pozitivnim NSCLC-om bile su poremećaj vida, mučnina, proljev, povraćanje, edem, konstipacija, povišene transaminaze, umor, smanjeni apetit, omaglica i neuropatija.
However, there was no observed induction in vivo when crizotinib was coadministered with the CYP3A probe substrate midazolam.
Međutim, nije primijećena indukcija in vivo kod istodobne primjene krizotiniba s probnim supstratom CYP3A, midazolamom.
• Ciclosporin, sirolimus and tacrolimus used in transplant patients.
• ciklosporinom, sirolimusom i takrolimusom - koriste se u bolesnika kojima je presađen organ.
• If you have reduced heart rate.
• ako imate smanjenu brzinu srčanih otkucaja.
Crizotinib significantly prolonged PFS, the primary objective of the study, compared to chemotherapy as assessed by IRR.
Krizotinib je značajno produljio PFS, primarni cilj ispitivanja, u usporedbi s kemoterapijom prema procjeni IRR-om.
The most serious adverse reactions in 1722 patients with either ALK-positive or ROS1-positive advanced NSCLC were hepatotoxicity, ILD/pneumonitis, neutropenia, and QT interval prolongation (see section 4.4).
Najozbiljnije nuspojave u 1722 bolesnika bilo s ALK-pozitivnim ili ROS1-pozitivnim uznapredovalim NSCLC-om bile su hepatotoksičnost, IBP/pneumonitis, neutropenija i produljenje QT-intervala (vidjeti dio 4.4).
NAME OF THE MARKETING AUTHORISATION HOLDER Pfizer Europe MA EEIG (as MAH logo)
Pfizer Europe MA EEIG (logo nositelja odobrenja)
• Second dose reduction: XALKORI 250 mg taken orally once daily
• drugo smanjenje doze: XALKORI 250 mg, primijenjen peroralno jedanput na dan
For patients without baseline brain metastases, the median IC-TTP was not reached in either the crizotinib (N=132) or the chemotherapy arms (N=131) (HR=0.69 [95% CI: 0.33, 1.45]; 1-sided p-value=0.1617).
Za bolesnike bez moždanih metastaza na početku ispitivanja, medijan IC-TTP nije dostignut u skupini krizotiniba (N=132) ili kemoterapijskoj skupini (N=131) (HR=0,69 [95% CI: 0,33; 1,45]; 1-strana p-vrijednost=0,1617).
In vitro studies in human liver microsomes demonstrated that crizotinib is a time-dependent inhibitor of CYP2B6 and CYP3A (see section 4.5).
Ispitivanja na ljudskim jetrenim mikrosomima in vitro pokazala su da je krizotinib inhibitor CYP2B6 i CYP3A ovisan o vremenu (vidjeti dio 4.5).
In randomised Phase 3 Study 1014, increases to Grade 3 or 4 ALT or AST elevations were observed in 15% and 8% of patients receiving crizotinib versus 2% and 1% of patients receiving chemotherapy.
U randomiziranom Ispitivanju 1014 Faze 3, povišenja do stupnja 3 ili 4 ALT-a ili AST-a opažena su u 15% i 8% bolesnika koji su primali krizotinib naspram 2% i 1% bolesnika koji su primali kemoterapiju.
Fifty-eight of 84 (69%) patients treated with crizotinib and 17 of 119 (14%) patients treated with chemotherapy continued treatment for at least 3 weeks after objective disease progression.
Pedeset osam od 84 (69%) bolesnika liječenih krizotinibom, i 17 od 119 (14%) bolesnika liječenih kemoterapijom, nastavilo je liječenje najmanje 3 tjedna nakon objektivne progresije bolesti.
Across clinical studies (n=1722), 19 (1.1%) patients treated with crizotinib had any grade cardiac failure, 8 (0.5%) patients had Grade 3 or 4, and 3 (0.2%) patients had fatal outcome.
U kliničkim ispitivanjima (n=1722), 19 (1,1%) bolesnika liječenih krizotinibom imalo je zatajenje srca bilo kojeg stupnja, 8 (0,5%) bolesnika stupnja 3 ili 4, a 3 (0,2%) bolesnika imala su smrtni ishod. i.
In vitro studies indicated that clinical drug-drug interactions are unlikely to occur as a result of crizotinib-mediated inhibition of the metabolism of medicinal products that are substrates for CYP1A2, CYP2C8, CYP2C9, CYP2C19 or CYP2D6.
Ispitivanja in vitro pokazala su da nisu vjerojatne kliničke interakcije s drugim lijekovima kao posljedica krizotinibom posredovane inhibicije metabolizma lijekova koji su supstrati za CYP1A2, CYP2C8, CYP2C9, CYP2C19 ili CYP2D6.
In vitro studies suggest that crizotinib is a substrate for P-glycoprotein (P-gp).
Ispitivanja in vitro ukazuju na to da je krizotinib supstrat P-glikoproteina (P-gp).
Findings observed in the female reproductive tract included single-cell necrosis of ovarian follicles of a rat given 500 mg/kg/day for 3 days.
Nalazi na ženskim spolnim organima uključuju nekrozu pojedinačnih stanica folikula u jajnicima štakorica koje su primale dozu od 500 mg/kg na dan tijekom 3 dana.
Patients with or without pre-existing cardiac disorders, receiving crizotinib, should be monitored for signs and symptoms of heart failure (dyspnoea, oedema, rapid weight gain from fluid retention).
Bolesnike s postojećim srčanim oboljenjima i one bez njih koji primaju krizotinib potrebno je nadzirati zbog moguće pojave znakova i simptoma zatajenja srca (dispneje, edema, ubrzanog porasta tjelesne težine uslijed zadržavanja tekućine).
No patients in the crizotinib arm of randomised Phase 3 Studies 1007 and 1014, and single arm Study 1005 were >85 years.
Niti jedan bolesnik u skupini krizotiniba u randomiziranim Ispitivanjima 1007 i 1014 faze 3 i u Ispitivanju 1005 s jednom skupinom bolesnika nije imao >85 godina.
Complete blood counts including differential white blood cell counts should be monitored as clinically indicated, with more frequent repeat testing if Grade 3 or 4 abnormalities are observed, or if fever or infection occurs.
Potrebno je kontrolirati kompletnu krvnu sliku, uključujući i diferencijalnu krvnu sliku, kako je klinički indicirano, a pretrage treba češće ponavljati ako se uoče odstupanja stupnja 3 ili 4 ili ako nastupi vrućica ili infekcija.
In vitro studies in human hepatocytes indicated that clinical drug-drug interactions are unlikely to occur as a result of crizotinib-mediated induction of the metabolism of medicinal products that are substrates for CYP1A2.
Ispitivanja na ljudskim hepatocitima in vitro pokazala su da nisu vjerojatne kliničke interakcije s drugim lijekovima kao posljedica krizotinibom posredovane indukcije metabolizma lijekova koji su supstrati za CYP1A2.
Crizotinib was aneugenic in an in vitro micronucleus assay in Chinese Hamster Ovary cells and in an in vitro human lymphocyte chromosome aberration assay.
Krizotinib se pokazao aneugenim u in vitro mikronukleusnom testu na stanicama jajnika kineskog hrčka i u in vitro testu kromosomske aberacije na ljudskim limfocitima.
XALKORI dose modification - non-haematological toxicities CTCAEa Grade
Tablica 2: Prilagodba doze lijeka XALKORI - nehematološka toksičnost Stupanj težine prema CTCAE
Significantly greater improvement in global QOL was observed in the crizotinib arm compared to the chemotherapy arm (overall difference in change from baseline scores 13.8; p-value <0.0001).
Značajno veće poboljšanje u globalnoj kvaliteti života zapaženo je u skupini krizotiniba u usporedbi s kemoterapijskom skupinom (ukupna razlika u promjeni u odnosu na početne bodove 13,8; p-vrijednost <0,0001).
• Atazanavir, ritonavir, cobicistat, used to treat HIV infections/AIDS.
• atazanavir, ritonavir, kobicistat - koriste se za liječenje HIV infekcije/SIDA-e.
Agents whose plasma concentrations may be altered by crizotinib
Lijekovi čiju koncentraciju u plazmi može promijeniti krizotinib
Findings observed in the male reproductive tract included testicular pachytene spermatocyte degeneration in rats given ≥50 mg/kg/day for 28 days (approximately 1.1-fold human clinical exposure based on AUC).
Nalazi na muškim spolnim organima uključuju pahitensku degeneraciju spermatocita u testisima štakora koji su primali dozu od ≥ 50 mg/kg na dan tijekom 28 dana (približno 1,1 puta veća izloženost u odnosu na kliničku izloženost u ljudi na temelju AUC-a).
Therefore, crizotinib may have the potential to increase plasma concentrations of coadministered drugs that are metabolized predominantly by UGT1A1 (e.g., raltegravir, irinotecan) or UGT2B7 (e.g., morphine, naloxone).
Ipak ponekad je učinak krizotiniba povećanje koncentracije u plazmi istodobno primijenjenih lijekova koji se metaboliziraju prvenstveno preko UGT1A1 (npr. raltegravir, irinotekan) ili UGT2B7 (npr. morfin, nalokson).
The effect of renal function as measured by baseline CLcr on observed crizotinib steady-state trough concentrations (Ctrough, ss) was evaluated.
Ocjenjivan je učinak funkcije bubrega mjerenjem početne vrijednosti CLcr-a na opaženim najnižim koncentracijama krizotiniba u stanju dinamičke ravnoteže (Ctrough, ss).
Efficacy data from ROS1-positive advanced NSCLC patients from Study 1001 are provided in Table 7.
Podaci o djelotvornosti u bolesnika s ROS1-pozitivnim uznapredovalim NSCLC-om iz Ispitivanja 1001 nalaze se u tablici 7.
The most frequent adverse reactions (≥3%) associated with dose reductions were elevated transaminases and neutropenia.
Najčešće nuspojave (≥3%) povezane sa smanjenjem doze bile su povišenje transaminaza i neutropenija.
In 1722 patients treated with crizotinib with either ALK-positive or ROS1-positive NSCLC across clinical studies, the most frequent adverse reactions (≥3%) associated with dosing interruptions were neutropenia, elevated transaminases, vomiting, and nausea.
U 1722 bolesnika liječenih krizotinibom s ALK-ili ROS1pozitivnim NSCLC-om u kliničkim ispitivanjima, najčešće nuspojave (≥3%) povezane s prekidom terapije su bile neutropenija, povišene transaminaze, povraćanje i mučnina.
The central tendency analysis indicated that the largest mean change from baseline in QTcF was 12.3 msec (95% CI 5.1-19.5 msec, least squares mean [LS] from Analysis of Variance [ANOVA]) and occurred at 6 hours post-dose on Cycle 2 Day 1.
Analiza središnje tendencije pokazala je da je najveća srednja vrijednost promjene u odnosu na početne vrijednosti QTcF-intervala bila 12,3 msek (95% CI 5,1-19,5 msek, srednja vrijednost procijenjena metodom najmanjih kvadrata [LS] iz analize varijance [ANOVA]) i javila se 6 sati nakon doze 1. dana 2. ciklusa.
Efficacy data from Studies 1001 and 1005 are provided in Table 6.
U Tablici 6 prikazani su podaci o djelotvornosti u Ispitivanjima 1001 i 1005.
Sixty-five of 89 (73%) patients treated with crizotinib and 11 of 132 (8.3%) patients treated with chemotherapy continued treatment for at least 3 weeks after objective disease progression.
Šezdeset pet od 89 (73%) bolesnika liječenih krizotinibom i 11 od 132 (8,3%) bolesnika liječenih kemoterapijom nastavilo je liječenje najmanje 3 tjedna nakon objektivne progresije bolesti.
In vitro studies indicated that crizotinib is an inhibitor of CYP2B6.
In vitro ispitivanja pokazala su da je krizotinib inhibitor enzima CYP2B6.
• Increased blood levels of creatinine (may indicate that kidneys are not functioning properly).
• povišene razine kreatinina u krvi (mogu ukazivati na neispravan rad bubrega).
Number of deaths, n (%) Overall Survivalc [median (95% CI)] months
Broj smrtnih slučajeva, n (%) Ukupno preživljenje c [medijan (95% CI)] mjeseci
The median duration of treatment was 22.4 months (95% CI: 15.0, 35.9).
Medijan trajanja liječenja iznosio je 22,4 mjeseca (95% CI: 15,0; 35,9).
Patients could continue treatment as assigned beyond the time of RECIST-defined disease progression at the discretion of the investigator if the patient was perceived to be experiencing clinical benefit.
Bolesnici su mogli nastaviti liječenje nakon vremena progresije bolesti definirane RECIST-om prema odluci ispitivača ako se smatralo da bolesnik ima kliničku korist.