natgillin/translations-raw huggingface dataset:
Hazard ratio (95% C. I.) Log rank p-value
Mediana vrednost (95% interval zaupanja)
(0.59-0.98) 0.033
(0, 59- 0, 98)
Topotecan/ Cisplatin
topotekan/ cisplatin
Median (95% C. I.)
Mediana vrednost (95% interval zaupanja)
8.8 (6.4, 11.5)
8, 8 (6, 4; 11, 5)
15.7 (11.9, 17.7)
15, 7 (11, 9; 17, 7)
Hazard ratio (95% C. I.)
Razmerje tveganja (95% interval zaupanja)
0.51 (0.31, 0.82)
0, 51 (0, 31; 0, 82)
Patients with Prior Cisplatin Chemoradiotherapy
Bolnice s predhodno kemoterapijo s cisplatinom
Median (95% C. I) Hazard ratio (95% C. I.)
Mediana vrednost (95% interval zaupanja)
5.9 (4.7, 8.8) 0.85 (0.59,
5, 9 (4, 7; 8, 8)
7.9 (5.5, 10.9) 1.21)
1, 21)
In patients (n=39) with recurrence within 180 days after chemoradiotherapy with cisplatin, the median survival in the topotecan plus cisplatin arm was 4.6 months (95% C. I.:
Pri bolnicah (n = 39) s ponovitvijo v 180 dneh po kemoradioterapiji s cisplatinom je bila mediana vrednost preživetja v skupini, ki je prejemala topotekan in cisplatin, 4, 6 meseca (95% interval zaupanja:
2.6, 6.1) versus 4.5 months (95%C. I.:
2, 6; 6, 1), v skupini, ki je prejemala cisplatin, pa 4, 5 meseca (95% intervala zaupanja:
2.9, 9.6) for the cisplatin arm with an hazard ratio of 1.15 (0.59, 2.23).
2, 9; 9, 6), razmerje tveganja 1, 15 (0, 59; 2, 23).
In those (n=102) with recurrence after 180 days, the median survival in the topotecan plus cisplatin arm was 9.9 months (95% C. I.:
Pri bolnicah (n = 102) s ponovitvijo po 180 dneh je bila mediana vrednost preživetja v skupini, ki je prejemala topotekan in cisplatin, 9, 9 meseca (95% interval zaupanja:
7, 12.6) versus 6.3 months (95%C. I.:
7; 12, 6) v skupini, ki je prejemala cisplatin, pa 6, 3 meseca (95% interval zaupanja:
4.9, 9.5) for the cisplatin arm with an hazard ratio of 0.75 (0.49, 1.16).
4, 9; 9, 5), razmerje tveganja 0, 75 (0, 49; 1, 16).
In an open-label trial involving children (n = 108, age range: infant to 16 years) with recurrent or progressive solid tumours, topotecan was administered at a starting dose of 2.0 mg/ m2 given as a 30- minute infusion for 5 days repeated every 3 weeks for up to one year depending on response to therapy.
Zdravljenje se je ponavljalo vsake 3 tedne in trajalo do 1 leta, odvisno od odziva na zdravljenje.
Tumour types included were Ewing's Sarcoma/ primitive neuroectodermal tumour, neuroblastoma, osteoblastoma, and rhabdomyosarcoma.
Ewingov sarkom/ primitivni nevroektodermalni tumor, nevroblastom, osteoblastom in rabdomiosarkom.
In this study, forty-six (43%) patients received G-CSF over 192 (42.1%) courses; sixty-five (60%) received transfusions of Packed Red Blood Cells and fifty (46%) of platelets over 139 and 159 courses (30.5% and 34.9%) respectively.
V tej študiji je šestinštirideset (43%) bolnikov po 192 (42, 1%) ciklih prejelo G- CSF, petinšestdeset (60%) bolnikov je po 139 (30, 5%) ciklih prejelo transfuzijo
Based on the dose-limiting toxicity of myelosuppression, the maximum tolerated dose (MTD) was established at 2.0 mg/ m2/ day with G-CSF and 1.4 mg/ m2/ day without G- CSF in a pharmacokinetic study in paediatric patients with refractory solid tumours (see section 5.2).
Pri otrocih z neodzivnimi solidnimi tumorji je bil v farmakokinetični študiji na osnovi od odmerka pogojene toksičnosti za mielosupresijo določen največji tolerantni odmerek 2, 0 mg/ m2/ dan pri uporabi G- CSF in 1, 4 mg/ m2/ dan brez uporabe G- CSF (glejte poglavje 5. 2).
Following intravenous administration of topotecan at doses of 0.5 to 1.5 mg/ m2 as a 30 minute infusion daily for five days, topotecan demonstrated a high plasma clearance of 62 l/ h (SD 22), 10 corresponding to approximately 2/ 3 of liver blood flow.
Ugotovili so, da je plazemski očistek topotekana po intravenskem infundiranju v odmerku 0, 5−1, 5 mg/ m2 5 zaporednih dni pri času infuzije 30 minut visok, in sicer 62 l/ h (SD 22), kar pomeni približno 2/ 3 pretoka krvi skozi jetra.
Topotecan also had a high volume of distribution, about 132 l, (SD 57) and a relatively short half-life of 2-3 hours.
Topotekan ima tudi velik volumen porazdelitve, približno 132 l (SD 57), in sorazmerno kratko razpolovno dobo, 2- 3 ure.
There is little or no accumulation of topotecan with repeated daily dosing and there is no evidence of a change in the PK after multiple doses.
Prav tako ni znakov, da bi se farmakokinetika po večkratnem odmerjanju spremenila.
Preclinical studies indicate plasma protein binding of topotecan is low (35%) and distribution between blood cells and plasma was fairly homogeneous.
Predklinične študije kažejo, da se topotekan le malo veže na beljakovine v plazmi (35%), precej enakomerno pa se razporedi med krvnimi celicami in plazmo.
Metabolism accounts for < 10% of the elimination of topotecan.
Presnova predstavlja < 10% izločanja topotekana.
An N-desmethyl metabolite, which was shown to have similar or less activity than the parent in a cell-based assay, was found in urine, plasma, and faeces.
Presnovek N- desmetil (za katerega so v celičnem testu dokazali, da ima podobno ali manjšo aktivnost kot izvorna učinkovina) so odkrili v urinu, plazmi in blatu.
The mean metabolite: parent AUC ratio was less than 10% for both total topotecan and topotecan lactone.
Tako za skupni topotekan kot topotekan lakton je srednje razmerje AUC- jev presnovek: izvorna učinkovina manjše od 10%.
An O-glucuronidation metabolite of topotecan and N-desmethyl topotecan has been identified in the urine.
V urinu so odkrili O- glukuronidacijski presnovek topotekana in N- desmetil topotekan.
Overall recovery of medicinal product-related material following five daily doses of topotecan was 71 to 76% of the administered IV dose.
Celokupno izločanje z zdravilom povezanih snovi po petih dnevnih odmerkih topotekana je bilo od 71 do 76% intravensko prejetega odmerka.
Approximately 51% was excreted as total topotecan and 3% was excreted as N-desmethyl topotecan in the urine.
Z urinom se izloči približno 51% skupnega topotekana in 3% N- desmetil topotekana.
Faecal elimination of total topotecan accounted for 18% while faecal elimination of N-desmethyl topotecan was 1.7%.
Ocenjeno je, da se z blatom izloči 18% skupnega topotekana in 1, 7% N - desmetil topotekana.
Overall, the N-desmethyl metabolite contributed a mean of less than 7% (range 4-9%) of the total medicinal product related material accounted for in the urine and faeces.
Presnovek N- desmetil predstavlja v povprečju manj kot 7% (razpon 4- 9%) skupnih z zdravilom povezanih snovi prisotnih v urinu in blatu.
The topotecan-O-glucuronide and N-desmethyl topotecan-O-glucuronide in the urine were less than 2.0%.
Topotekan- O- glukuronid in N - desmetil topotekan- O- glukuronid sta v urinu v manj kot 2, 0%.
In vitro data using human liver microsomes indicate the formation of small amounts of N- demethylated topotecan.
V raziskavi in vitro, v kateri so uporabili mikrosome človeških jeter, so opazili nastanek majhne količine N- demetiliranega topotekana.
In vitro, topotecan did not inhibit human P450 enzymes CYP1A2, CYP2A6, CYP2C8/ 9, CYP2C19, CYP2D6, CYP2E, CYP3A, or CYP4A nor did it inhibit the human cytosolic enzymes dihydropyrimidine or xanthine oxidase.
Prav tako ni zaviral citosolskih encimov dihidropirimidina in ksantinoksidaze pri človeku.
When given in combination with cisplatin (cisplatin day 1, topotecan days 1 to 5), the clearance of topotecan was reduced on day 5 compared to day 1 (19.1 L/ h/ m2 compared to 21.3 L/ h/ m2 [n=9]) (see section 4.5).
Pri dajanju v kombinaciji s cisplatinom (cisplatin 1. dan, topotekan od 1. do 5. dne) je bil 5. dan očistek topotekana v primerjavi s 1. dnem manjši (19, 1 l/ uro/ m2 v primerjavi s 21, 3 l/ uro/ m2 [n = 9]) (glejte poglavje 4. 5).
Plasma clearance in patients with hepatic impairment (serum bilirubin between 1.5 and 10 mg/ dl) decreased to about 67% when compared with a control group of patients.
Plazemski očistek pri bolnikih z jetrno okvaro (serumski bilirubin med 1. 5 in 10 mg/ dl) se je v primerjavi s kontrolno skupino znižal na približno 67%.
Topotecan half-life was increased by about 30% but no clear change in volume of distribution was observed.
Razpolovna doba topotekana se je podaljšala za 30%, volumen porazdelitve pa se ni bistveno spremenil.
Plasma clearance of total topotecan (active and inactive form) in patients with hepatic impairment only decreased by about 10% compared with the control group of patients.
Plazemski očistek celotnega topotekana (aktivne in neaktivne oblike) se je pri teh bolnikih v primerjavi s kontrolno skupino zmanjšal le za približno 10%.
Plasma clearance in patients with renal impairment (creatinine clearance 41-60 ml/ min.) decreased to about 67% compared with control patients.
Plazemski očistek pri bolnikih z ledvično okvaro (očistek kreatinina 41−60 ml/ min) se je v primerjavi s kontrolno skupino zmanjšal na približno 67%.
Volume of distribution was slightly decreased and thus half-life only increased by 14%.
Volumen porazdelitve je bil malo manjši, zato se je razpolovna doba podaljšala le za 14%.
In patients with moderate renal impairment topotecan plasma clearance was reduced to 34% of the value in control patients.
Pri bolnikih z zmerno hudo ledvično okvaro se je plazemski očistek zmanjšal na 34% vrednosti pri bolnikih v kontrolni skupini.
Mean half-life increased from 1.9 hours to 4.9 hours.
Srednja razpolovna doba se je z 1, 9 ure podaljšala na 4, 9 ur.
11 refractory solid tumours.
11 Pediatrični bolniki
The second study included a dose range of 2.0 mg/ m2 to 5.2 mg/ m2 in children (n = 8), adolescents (n = 3), and young adults (n = 3) with leukaemia.
V drugi študiji so otroci (n = 8), mladostniki (n = 3) in mlajši odrasli (n = 3) z levkemijo prejemali odmerek od 2, 0 mg/ m2 do 5, 2 mg/ m2.
Reconstituted and diluted solutions The product should be used immediately after reconstitution as it contains no antibacterial preservative.
Rekonstituirane in razredčene raztopine Pripravek je potrebno uporabiti takoj po rekonstituciji, saj ne vsebuje protibakterijskih konzervansov.
If reconstitution and dilution is performed under strict aseptic conditions (e. g. an LAF bench) the product should be used (infusion completed) within 12 hours at room temperature or 24 hours if stored at 2-8 0C after the first puncture of the vial.
Če priprava in redčenje potekata v strogo aseptičnih pogojih, na primer v napravi z laminarnim tokom zraka (LAF), je treba zdravilo porabiti (končati infuzijo) v 12 urah, v kolikor ga hranimo pri sobni temperaturi, oziroma v 24 urah, če ga takoj po prvem odprtju shranimo pri 2 do 8 °C.
HYCAMTIN 1 mg is supplied in 5 ml type I flint glass vials, together with 13 mm grey butyl rubber stoppers and 13 mm aluminium seals with plastic flip-off caps.
HYCAMTIN 1 mg je na voljo v 5- ml vialah iz kristalnega stekla (tip I), ki so opremljene s 13- mm sivimi zamaški iz butilne gume, zapečatene s 13- mm aluminijasto zaporko s plastičnim pokrovom (flip- off).
Not all pack sizes may be marketed.
12 Na trgu ni vseh navedenih pakiranj.
6.6 Special precautions for disposal and other handling 12 HYCAMTIN 1 mg vials must be reconstituted with 1.1 ml water for injections.
HYCAMTIN 1 mg viale morate rekonstituirati z 1, 1 ml vode za injekcije.
Since HYCAMTIN contains a 10% overage, the clear, reconstituted solution is yellow to yellow-green in colour and provides 1 mg per ml of topotecan.
Ker vsebuje HYCAMTIN 10% prebitek, ima pripravljena bistra, rumena do rumeno- zelena raztopina koncentracijo 1 mg topotekana na ml.
Further dilution of the appropriate volume of the reconstituted solution with either 0.9% w/ v sodium chloride intravenous infusion or 5% w/ v glucose intravenous infusion is required to a final concentration of between 25 and 50 microgram/ ml.
Ustrezno količino tako pripravljene raztopine morate še dodatno razredčiti z 0, 9% intravensko infuzijsko raztopino natrijevega klorida ali s 5% intravensko infuzijsko raztopino glukoze, da nastane končni pripravek s koncentracijo med 25 in 50 mikrogramov/ ml.
The normal procedures for proper handling and disposal of anticancer medicinal products should be adopted, namely: − Personnel should be trained to reconstitute the medicinal product. − Pregnant staff should be excluded from working with this medicinal product. − Personnel handling this medicinal product during reconstitution should wear protective clothing including mask, goggles and gloves. − All items for administration or cleaning, including gloves, should be placed in high-risk, waste disposal bags for high-temperature incineration.
- Osebje, ki pripravlja in daje zdravilo, mora med rekonstitucijo nositi zaščitna oblačila, masko,
Liquid waste may be flushed with large amounts of water. − Accidental contact with the skin or eyes should be treated immediately with copious amounts of water.
- Vse pripomočke, ki jih potrebujete pri dajanju zdravila ali čiščenju, tudi rokavice, morate
5 vials 1 vial
5 vial 1 viala
12/ 11/ 1996 Date of last renewal:
12/ 11/ 1996 Datum zadnjega podaljšanja dovoljenja za promet:
Each vial contains 4 mg topotecan (as hydrochloride).
Vsaka viala vsebuje 4 mg topotekana (v obliki klorida).
14 Subsequent doses Topotecan should not be re-administered unless the neutrophil count is ≥ 1 x 109/ l, the platelet count is ≥ 100 x 109/ l, and the haemoglobin level is ≥ 9g/ dl (after transfusion if necessary).
14 Nadaljevalni odmerki Pred naslednjo uporabo topotekana mora biti število nevtrofilcev ≥ 1 x 109/ l, število trombocitov ≥ 100 x 109/ l, vrednost hemoglobina pa ≥ 9 g/ dl (po transfuziji, če je le- ta potrebna).
If dose reduction is chosen for patients who experience severe neutropenia (neutrophil count < 0.5 x 109/ l) for 7 days or more, or severe neutropenia associated with fever or infection, or who have had treatment delayed due to neutropenia, the dose should be reduced by 0.25 mg/ m2/ day to 1.25 mg/ m2/ day (or subsequently down to 1.0 mg/ m2/ day if necessary)
Če izberete zmanjšanje odmerka priolnikih s hudo nevtropenijo (število nevtrofilcev < 0, 5 x 109/ l), ki traja 7 ali več dni, ali s hudo nevtropenijo z zvišano telesno temperaturo ali okužbo, ali pri bolnikih, ki jim je bilo treba zdravljenje odložiti zaradi nevtropenije, morate odmerek zmanjšati za 0, 25 mg/ m2/ dan na 1, 25 mg/ m2/ dan (ali ga po potrebi še dodatno zmanjšati do 1, 0 mg/ m2/ dan).
The recommended monotherapy dose of topotecan in patients with ovarian or small cell lung cancer and a creatinine clearance between 20 and 39 ml/ min is 0.75 mg/ m2 / day for 5 consecutive days.
Priporočeni odmerek topotekana kot samostojnega zdravila pri zdravljenju bolnic z rakom jajčnika in bolnikov z drobnoceličnim pljučnim rakom, ki imajo očistek kreatinina med 20 in 39 ml/ min je 0, 75 mg/ m2 na dan, 5 zaporednih dni.
Combination therapy (Cervical carcinoma) In clinical studies with topotecan in combination with cisplatin for the treatment of cervical cancer, therapy was only initiated in patients with serum creatinine less than or equal to 1.5 mg/ dL.
Kombinirano zdravljenje (karcinom materničnega vratu) Med kliničnimi študijami zdravljenja raka materničnega vratu je bilo zdravljenje s topotekanom v kombinaciji s cisplatinom uvedeno le pri bolnicah, ki so imele vrednost serumskega kreatinina manjšo ali enako 1, 5 mg/ dl.
If, during topotecan/ cisplatin combination therapy serum creatinine exceeds 1.5 mg/ dL, it is recommended that the full prescribing information be consulted for any advice on cisplatin dose reduction/ continuation.
Če se pri bolnicah z rakom
If cisplatin is discontinued, there are insufficient data regarding continuing monotherapy with topotecan in patients with cervical cancer.
15 materničnega vratu zdravljenje s cisplatinom ukine, za nadaljevanje zdravljenja samo s topotekanom ni zadostnih podatkov.
15 Paediatrics The experience in children is limited, therefore no recommendation for treatment of paediatric patients with HYCAMTIN can be given (see sections 5.1 and 5.2).
Pediatrični bolnikiIzkušnje pri otrocih so nezadostne, zato ni mogoče dati priporočil za zdravljenje pediatričnih bolnikov z zdravilom HYCAMTIN (glejte poglavji 5. 1 in 5. 2).
This should be taken into account, e. g. in case patients at increased risk for tumour bleeds are considered for therapy.
To je treba upoštevati, npr. pri bolnikih, pri katerih obstaja večje tveganje za pojav krvavitve tumorja.
A small number of hepatically impaired patients (serum bilirubin between 1.5 and 10 mg/ dl) were given 1.5 mg/ m2 for five days every three weeks.
Le manjše število bolnikov z jetrno okvaro (vrednost serumskega bilirubina med 1, 5 in 10 mg/ dl) je prejelo odmerek 1, 5 mg/ m2 po 5 dni na vsake tri tedne.
4.5 Interaction with other medicinal products and other forms of interaction
16 4. 5 Medsebojno delovanje z drugimi zdravili in druge oblike interakcij
Topotecan does not inhibit human P450 enzymes (see Section 5.2).
Topotekan ne zavira encimov človeškega citokroma P450 (glejte poglavje 5. 2).
In a population study, the co- 16 administration of granisetron, ondansetron, morphine or corticosteroids did not appear to have a significant effect on the pharmacokinetics of total topotecan (active and inactive form).
V populacijski študiji niso zasledili, da bi sočasno dajanje granisetrona, ondansetrona, morfina ali kortikosteroidov pomembneje vplivalo na farmakokinetiko celokupnega topotekana (aktivne in neaktivne oblike).
Additional adverse events were seen when topotecan was given in combination with cisplatin, however, these events were seen with cisplatin monotherapy and not attributable to topotecan.
17 Pri dajanju topotekana v kombinaciji s cisplatinom so opazili dodatne neželene učinke, vendar pa so bili ti neželeni učinki opaženi tudi pri samostojnem zdravljenju s cisplatinom in jih niso pripisali topotekanu.
17 The integrated safety data of topotecan monotherapy are presented below.
V nadaljevanju navajamo povzetek podatkov o varnosti topotekana kot samostojnega zdravila.
Blood and lymphatic system disorders Very common: febrile neutropenia, neutropenia (see Gastrointestinal disorders), thrombocytopenia, anaemia, leucopenia.
Bolezni krvi in limfatičnega sistema Zelo pogosti: nevtropenija s sočasno povišano telesno temperaturo, nevtropenija (glejte Bolezni prebavil), trombocitopenija, anemija, levkopenija.
Hepato-biliary disorders Common: hyperbilirubinaemia.
Bolezni jeter, žolčnika in žolčevodov Pogosti: hiperbilirubinemija
The frequencies associated with the haematological and non-haematological adverse events listed below represent the adverse event reports considered to be related/ possibly related to topotecan 18 therapy.
18 V nadaljevanju navedena pogostnost hematoloških in nehematoloških neželenih dogodkov se nanaša na poročila o neželenih dogodkih, ki so bili ali bi lahko bili povezani z zdravljenjem s topotekanom.
Haematological Neutropenia:
Hematološki Nevtropenija:
19 The anti-tumour activity of topotecan involves the inhibition of topoisomerase-I, an enzyme intimately involved in DNA replication as it relieves the torsional strain introduced ahead of the moving replication fork.
Protitumorsko delovanje topotekana vključuje zaviranje encima topoizomeraze I, tesno povezanega s podvojevanjem DNA, saj sprošča torzijsko napetost, ki nastopa pred napredujočimi replikacijskimi vilicami.
84 days for oral topotecan + BSC, 90 days for BSC] and for whom retreatment with i. v. chemotherapy was not considered appropriate.
84 dni za zdravljenje s peroralnim topotekanom v kombinaciji z NPO; 90 dni za zdravljenje z NPO samo] in pri katerih zdravljenje z intravensko obliko kemoterapije ni bilo primerno.
18.3, 31.6] compared to 13.9 weeks [95% C. I.
Srednji čas preživetja bolnikov, ki so bili zdravljeni s peroralnim topotekanom v kombinaciji z NPO je bil 25, 9 tednov [95% interval zaupanja 18, 3; 31, 6] pri bolnikih, ki so bili zdravljeni z NPO samo pa 13, 9 tednov [95% interval zaupanja 11, 1; 18, 6] [p=0. 0104].
11.1, 18.6] for patients receiving BSC alone [p=0.0104].
Neslepljeno ocenjene navedbe bolnikov samih o simptomih so pokazale dosleden trend k boljšemu simptomatskemu stanju v skupini, zdravljeni s peroralnim topotekanom in NPO.
Patient self-reports of symptoms using an unblinded assessment showed a consistent trend for symptom benefit for oral topotecan + BSC.
Za oceno učinkovitosti peroralnega topotekana v primerjavi z intravenskim topotekanom pri bolnikih, ki se jim je pojavil relaps ≥ 90 dni po koncu ene predhodne sheme kemoterapije, sta bili narejeni ena
One Phase 2 study (Study 065) and one Phase 3 study (Study 396) were conducted to evaluate the efficacy of oral topotecan versus intravenous topotecan in patients who had relapsed ≥ 90 days after completion of one prior regimen of chemotherapy. (see Table 1).
20 študija 2. faze (študija 065) in ena študija 3. faze (študija 396) (glejte tabelo 1).
20 Table 1.
Tabela 1.
Hazard ratio (95% CI) total number of patients treated.
Razmerje tveganja (95% IZ)
CI = Confidence interval.
IZ = interval zaupanja
In a randomised, comparative phase III trial conducted by the Gynaecological Oncology Group (GOG 0179), topotecan plus cisplatin (n=147) was compared with cisplatin alone (n=146) for the treatment of histologically confirmed persistent, recurrent or Stage IVB carcinoma of the cervix where curative treatment with surgery and/ or radiation was not considered appropriate.
Randomizirano primerjalno preskušanje III. faze, ki ga je izvedla ginekološka onkološka skupina (GOG 0179), je primerjalo topotekan in cisplatin (n = 147) s cisplatinom samim (n = 146) pri zdravljenju histološko potrjenega persistentnega rekurentnega karcinoma materničnega vratu ali karcinoma materničnega vratu v stadiju IVB, kjer kurativno zdravljenje s kirurškim posegom in/ ali radiacijo ni bilo primerno.
Topotecan plus cisplatin had a statistically significant benefit in overall survival relative to cisplatin monotherapy after adjusting for interim analyses (Log-rank p =0.033).
Pri vmesni analizi je imela kombinacija topotekana in cisplatina statistično pomembno korist na skupno preživetje v primerjavi z zdravljenjem s samim cisplatinom (log- rank p = 0, 033).
21 Study results Study GOG-0179 ITT population
21 Rezultati študije GOG- 0179
In this study, forty-six (43%) patients received G-CSF over 192 (42.1%) courses; sixty-five (60%) received transfusions of Packed Red Blood Cells and fifty (46%) of platelets over 139 and 159 courses (30.5% and 34.9%) respectively.
V tej študiji je šestinštirideset (43%) bolnikov po 192 (42, 1%) ciklih prejelo G- CSF, petinšestdeset (60%) bolnikov je po 139 (30, 5%) ciklih prejelo transfuzijo eritrocitov, petdeset (46%) bolnikov pa po 159 (34, 9%) ciklih transfuzijo trombocitov.
Based on the dose-limiting toxicity of myelosuppression, the maximum tolerated dose (MTD) was established at 2.0 mg/ m2/ day with G-CSF and 1.4 mg/ m2/ day without G- CSF in a pharmacokinetic study in paediatric patients with refractory solid tumours (see section 5.2).
22 toksičnosti za mielosupresijo določen največji tolerantni odmerek 2, 0 mg/ m2/ dan pri uporabi G- CSF in 1, 4 mg/ m2/ dan brez uporabe G- CSF (glejte poglavje 5. 2).
Following intravenous administration of topotecan at doses of 0.5 to 1.5 mg/ m2 as a 30 minute infusion daily for five days, topotecan demonstrated a high plasma clearance of 62 l/ h (SD 22), corresponding to approximately 2/ 3 of liver blood flow.
Ugotovili so, da je plazemski očistek topotekana po intravenskem infundiranju v odmerku 0, 5−1, 5 mg/ m2 5 zaporednih dni pri času infuzije 30 minut visok, in sicer 62 l/ h (SD 22), kar pomeni približno 2/ 3 pretoka krvi skozi jetra.
Topotecan also had a high volume of 22 distribution, about 132 l, (SD 57) and a relatively short half-life of 2-3 hours.
Topotekan ima tudi velik volumen porazdelitve, približno 132 l (SD 57), in sorazmerno kratko razpolovno dobo, 2- 3 ure.
23 Paediatrics
23 Pediatrični bolniki
The pharmacokinetics of topotecan given as a 30-minute infusion for 5 days were evaluated in two studies.
Farmakokinetika topotekana, ki so ga dajali v obliki 30- minutne infuzije 5 dni, je bila ovrednotena v dveh študijah.