natgillin/translations-raw huggingface dataset:
EBMT-kriterier g Alle randomiserede patienter med sekretorisk sygdom * Opdatering af overlevelsesdata baseret på en median opfølgning på 60,1 måneder mdr.= måneder CI = konfidensinterval.
EBMT criteria g All randomised patients with secretory disease * Survival update based on a median duration of follow-up at 60.1 months mo: months
Der observeredes ikke nogen nye sikkerhedsproblemer, når Bortezomib Accord blev føjet til standard-kemoterapiregimet for pædiatrisk præ-B-celle ALL.
No new safety concerns were observed when Bortezomib Accord was added to the standard paediatric pre B cell ALL chemotherapy backbone.
Der skal derfor udvises forsigtighed ved håndtering og anvendelse af Bortezomib Accord.
Therefore, caution should be used during handling and preparation of Bortezomib Accord.
Der blev observeret en statistisk signifikant forbedring af overlevelsen i Bz+M+Pbehandlingsgruppen (HR=0,695; p=0,00043) til trods for efterfølgende behandlinger, inklusive regimer baseret på bortezomib.
A statistically significant survival benefit in favour of the Bz+M+P treatment group was observed (HR=0.695; p=0.00043) despite subsequent therapies including bortezomib-based regimens.
Kan være dødelig hvis det indgives via andre administrationsveje.
May be fatal if given by other routes.
Patienter, der opnår respons eller stabiliseret sygdom efter 4 cyklusser med denne kombinationsbehandling, kan fortsætte behandlingen, med samme kombination i højst 4 yderligere cyklusser.
Patients achieving a response or a stable disease after 4 cycles of this combination therapy can continue to receive the same combination for a maximum of 4 additional cycles.
Accord blev kun administreret i blok 1 og 2 for at undgå potentiel overlappende toksicitet med coadministrerede lægemidler i blok 3.
Bortezomib Accord was administered only in Blocks 1 and 2 to avoid potential overlapping toxicities with coadministered drugs in Block 3.
Dosisjusteringer til transplantationsegnede patienter
Dosage adjustments for transplant eligible patients
Antiviral profylakse blev administreret til 26 % af patienterne i Bz+M+P-gruppen.
Antiviral prophylaxis was administered to 26% of the patients in the Bz+M+P arm.
Patienter, der opnår et komplet respons, kan fortsætte behandlingen i mindst 2 cyklusser efter første tegn på komplet respons, selv om dette kræver behandling i flere end 8 cyklusser.
Patients achieving a complete response can continue treatment for at least 2 cycles after the first evidence of complete response, even if this requires treatment for more than
Posteriort reversibelt encefalopatisk syndrom (PRES) Der er indberettet PRES hos patienter, der fik bortezomib.
Posterior reversible encephalopathy syndrome (PRES) There have been reports of PRES in patients receiving bortezomib.
Indehaveren af markedsføringstilladelsen skal sikre, at læger og sundhedspersonale, der beskæftiger sig med ordination, udlevering, håndtering eller administration af Bortezomib Accord, forsynes med uddannelsespakken.
The MAH shall ensure thatall healthcare professionals involved in the prescribing, dispensing, handling or administration of Bortezomib Accord are provided with educational material.
Patienter i henholdsvis BzTDx- og TDx-gruppen havde en gennemsnitsalder på 57 versus 56 år, 99 % versus 98 % af patienterne var kaukasere og 58 % versus 54 % var mænd.
Patients in the BzTDx and TDx groups respectively had a median age of 57 versus 56 years, 99% versus 98% patients were Caucasians, and 58% versus 54% were males.
Grad ≥ 3 ikke- hæmatologisk toksicitet, som anses for relateret til Bortezomib Accord
Grade ≥ 3 non-haematological toxicities considered to be related to Bortezomib Accord
Det anbefales ligeledes, at responderende patienter, som ikke opnår fuldstændig remission, gennemgår i alt 8 behandlingscyklusser med bortezomib.
It is also recommended that responding patients who do not achieve a complete remission receive a total of 8 cycles of bortezomib therapy.
Tidlig og regelmæssig monitorering for symptomer på behandlingsrelateret neuropati og neurologisk evaluering skal overvejes hos patienter, der får bortezomib i kombination med lægemidler, der vides at være forbundet med neuropati (fx thalidomid), og passende dosisreduktion eller behandlingsseponering skal overvejes.
Early and regular monitoring for symptoms of treatment-emergent neuropathy with neurological evaluation should be considered in patients receiving bortezomib in combination with medicinal products known to be associated with neuropathy (e.g. thalidomide) and appropriate dose reduction or treatment discontinuation should be considered.
Tabel 16: Effektresultater fra studie LYM-3002
Table 16: Efficacy results from study LYM-3002
Mandlige patienter og kvindelige fertile patienter skal anvende sikker kontraception under behandlingen og i 3 måneder efter behandlingen.
Male patients and female patients of childbearing potential must use effective contraceptive measures during and for 3 months following treatment.
Yderligere bivirkninger, som blev identificeret i forbindelse med brug af kombinationsbehandling (BzR-CAP), var hepatitis B-infektion (< 1 %) og myokardie-iskæmi (1,3 %).
Additional adverse drug reactions identified associated with the use of the combination therapy (BzR-CAP) were hepatitis B infection (< 1%) and myocardial ischaemia (1.3%).
Angioødem#, overfølsomhed*
Angioedema#, Hypersensitivity*
** Instrumentel ADL: Dækker madlavning, indkøb af dagligvarer eller tøj, brug af telefon, håndtering af penge osv. *** Personlig ADL: Dækker badning, på- og afklædning, spisning, toiletbesøg, indtagelse af medicin og oppegående.
** Instrumental ADL: refers to preparing meals, shopping for groceries or clothes, using telephone, managing money, etc; *** Self care ADL: refers to bathing, dressing and undressing, feeding self, using the toilet, taking medicinal products, and not bedridden.
Gastrointestinal toksicitet, inklusive kvalme, diaré, opkastning og forstoppelse, er meget almindelig ved behandling med bortezomib.
Gastrointestinal toxicity, including nausea, diarrhoea, vomiting and constipation are very common with bortezomib treatment.
Normal leverfunktion skal bekræftes, og der skal udvises forsigtighed ved patienter, der behandles med orale hypoglykæmika (se pkt.
Normal liver function should be confirmed and caution should be exercised in patients receiving oral hypoglycaemics (see section 4.5).
d Logrank-test justeret for stratifikationsfaktorer: ISS-score og antal tidligere linjer.
d Log rank test adjusted for stratification factors: ISS staging and number of prior lines.
Normal (CrCl ≥ 60 ml/min/1,73 m2, n=12), Mild (CrCl=40-59 ml/min/1,73 m2, n=10), Moderat (CrCl=20-39 ml/min/1,73 m2, n=9) og Alvorlig (CrCl < 20 ml/min/1,73 m2, n=3).
Normal (CrCL ≥ 60 ml/min/1.73 m2, n=12), Mild (CrCL=40-59 ml/min/1.73 m2, n=10), Moderate (CrCL=20-39 ml/min/1.73 m2, n=9), and Severe (CrCL < 20 ml/min/1.73 m2, n=3).
"Matchet par"-analysen er en statistisk metode i hvilken patienter i behandlingsgruppen (f.eks. bortezomib i kombination med dexamethason) og patienter i sammenligningsgruppen (f.eks. bortezomib) gøres sammenlignelige med hensyn til confounding faktorer ved individuelt at sammensætte forsøgspersonerne i par.
The matched-pair analysis is a statistical method in which patients in the treatment group (e.g. bortezomib in combination with dexamethasone) and patients in the comparison group (e.g. bortezomib) are made comparable with respect to confounding factors by individually pairing study subjects.
Intention to treat-populationb n=74
Intent to Treat Populationb n=74
• Hvis toksiciteten ikke forsvinder efter, at Bortezomib Accord har været indstillet som defineret ovenfor, skal Bortezomib Accord seponeres.
• If, after Bortezomib Accord has been held, the toxicity does not resolve, as defined above, then Bortezomib Accord must be discontinued.
Progressionsfri overlevelse, måneder 8,0
Progression Free Survival, months
Reducer Bortezomib Accord til 0,7 mg/m2 i første behandlingscyklus.
Reduce Bortezomib Accord to 0.7 mg/m2 in the first treatment cycle.
d p-værdi fra Cochran-Mantel-Haenszel chi-square-testen justeret for stratifikationsfaktorer; analyse ud fra behandling udelukker opdeling på tidligere behandling * CR+PR+MR **CR=CR, (IF-); nCR=CR (IF+) TTP = Tid til progression
d p-value from the Cochran-Mantel-Haenszel chi-square test adjusted for the stratification factors; analysis by line of therapy excludes stratification for therapeutic history * CR+PR+MR **CR=CR, (IF-); nCR=CR (IF+)
Den inkluderer desuden bivirkninger, som blev identificeret i BzR-CAP-armen, og som af investigatorerne blev anset for at have mindst en mulig eller sandsynlig årsagssammenhæng med bortezomib, baseret på historiske data i myelomatose-studierne.
Also included are adverse drug reactions identified in the BzR-CAP arm that were considered by investigators to have at least a possible or probable causal relationship to bortezomib based on historical data in the multiple myeloma studies.
Størstedelen af patienterne i begge grupper fuldførte behandlingen, 80 % i BzR-CAP-gruppen og 82 % i R-CHOP-gruppen.
The majority of the patients in both groups completed treatment, 80% in the BzR-CAP group and 82% in the R-CHOP group.
Bortezomib Accord må ikke administreres intratekalt.
Bortezomib Accord should not be administered intrathecally.
Fald, kontusion
Fall, Contusion
Systemorganklasse Frekvens
System Organ Class
h Inkluderer alle radiologiske CR+CRu+PR efter IRC uanset verificering ved knoglemarv og
h Include all radiological CR+CRu+PR by IRC regardless the verification by bone marrow and LDH.
I fase II-studiet kunne de patienter, som ikke havde en optimal respons på behandlingen med bortezomib alene, få højdosis dexamethason sammen med bortezomib.
In the Phase II study, patients who did not obtain an optimal response to therapy with bortezomib alone were able to receive high-dose dexamethasone in conjunction with bortezomib.
Patienter, der ikke opnåede et optimalt respons (mindre end et komplet respons [CR]) på behandlingen med bortezomib alene efter 4 cyklusser, fik desuden dexamethason 20 mg dagligt dagen før og efter administration af bortezomib.
Patients who did not obtain an optimal response (less than Complete Response [CR]) to therapy with bortezomib alone after 4 cycles were allowed to receive dexamethasone 20 mg daily on the day of and after bortezomib administration.
Der er gennemført et åbent, randomiseret, fase III noninferiority-studie til sammenligning af effekt og sikkerhed af subkutan administration af bortezomib versus intravenøs administration.
An open label, randomised, Phase III non-inferiority study compared the efficacy and safety of the subcutaneous administration of bortezomib versus the intravenous administration.
Følgende bivirkninger (grad ≥ 3) blev observeret med en hyppigere forekomst i behandlingsregimet med Bortezomib Accord sammenlignet med et historisk kontrolstudie, i hvilket baggrundsregimet blev givet alene: I blok 1 perifer sensorisk neuropati (3 % kontra 0 %), ileus (2,1 % kontra 0 %), hypoksi (8 % kontra 2 %).
The following adverse reactions (Grade ≥ 3) were observed at a higher incidence in the Bortezomib Accord containing treatment regimen as compared with a historical control study in which the backbone regimen was given alone: in Block 1 peripheral sensory neuropathy (3% versus 0%); ileus (2.1% versus 0%); hypoxia (8% versus 2%).
Bortezomib Accord en gang om ugen (cyklus 5-9)
Once weekly Bortezomib Accord (cycles 5-9)
Henholdsvis 42,9 % og 10,4 % af patienterne i BzR-CAP-armen var i alderen 65-74 år og ≥ 75 år.
42.9% and 10.4% of patients in the BzR-CAP arm were in the range 65-74 years and ≥ 75 years of age, respectively.
Instruktioner for rekonstitution Bortezomib Accord skal rekonstitueres af sundhedspersonale.
Instructions for reconstitution Bortezomib Accord must be reconstituted by a healthcare professional.
Patienter, der udviklede ortostatisk hypotension ved bortezomib (som intravenøs injektion) viste ikke tegn på ortostatisk hypotension før behandlingen med bortezomib.
Patients who developed orthostatic hypotension on bortezomib (injected intravenously) did not have evidence of orthostatic hypotension prior to treatment with bortezomib.
Bortezomib Accord indeholder det aktive stof bortezomib, som er en såkaldt proteasomhæmmer.
Bortezomib Accord contains the active substance bortezomib, a so-called ‘proteasome inhibitor'.
Din læge vil bestemme dosis ud fra din højde og vægt (areal af legemsoverflade).
Your doctor will work out your dose of Bortezomib Accord according to your height and weight (body surface area).
g P-værdi fra Cochran Mantel-Haenszel chi2 -test, med IPI og sygdomsstadie som stratifikationsfaktorer.
g P-value from the Cochran Mantel-Haenszel chi-square test, with IPI and stage of disease as stratification factors.
I BzR-CAP-gruppen fik 22,5 % af patienterne trombocyttransfusioner sammenlignet med 2,9 % af patienterne i R-CHOP-gruppen.
In the BzR-CAP group, 22.5% of patients received platelet transfusions compared to 2.9% of patients in the R-CHOP group.
Det Europæiske Lægemiddelagentur har dispenseret fra kravet om at fremlægge resultaterne af studier med bortezomib i alle undergrupper af den pædiatriske population ved myelomatose og ved mantlecelle-lymfom (se pkt.
The European Medicines Agency has waived the obligation to submit the results of studies with bortezomib in all subsets of the paediatric population in multiple myeloma and in mantle cell lymphoma (see section 4.2 for information on paediatric use).
Den mediane varighed af komplet respons var 42,1 måneder i BzR-CAP-gruppen sammenlignet med 18 måneder i R-CHOP-gruppen.
The median duration of complete response was 42.1 months in the BzR-CAP group compared with 18 months in the R-CHOP group.
Behandlingen med bortezomib forbindes almindeligvis med ortostatisk/postural hypotension.
Bortezomib treatment is commonly associated with orthostatic/postural hypotension.
Du kan ligeledes få Bortezomib Accord sammen med lægemidlerne pegyleret liposomal doxorubicin eller dexamethason.
You may also be given Bortezomib Accord together with the medicines pegylated liposomal doxorubicin or dexamethasone.
Der blev observeret en statistisk signifikant fordel (p < 0,001) for BzR-CAP-gruppen i forhold til R-CHOP-gruppen for TTP (median 30,5 kontra 16,1 måneder), TNT (median 44,5 kontra 24,8 måneder) og TFI (median 40,6 kontra 20,5 måneder).
A statistically significant benefit (p < 0.001) in favour of the BzR-CAP treatment group over the R-CHOP group was observed for TTP (median 30.5 versus 16.1 months), TNT (median 44.5 versus 24.8 months) and TFI (median 40.6 versus 20.5 months).
Kombinationsbehandling med rituximab, cyclophosphamid, doxorubicin og prednison (BzR-CAP)
Combination therapy with rituximab, cyclophosphamide, doxorubicin and prednisone (BzR-CAP)
De to behandlingsgrupper var sammenlignelige, hvad angår den samlede forekomst af alle grader af blødningshændelser (6,3 % i BzR-CAP-gruppen og 5,0 % i R-CHOP-gruppen) såvel som blødningshændelser af grad 3 og højere (BzR-CAP: 4 patienter [1,7 %]; R-CHOP: 3 patienter [1,2 %]).
The two treatment groups were similar with regard to the overall incidence of all-grade bleeding events (6.3% in the BzR-CAPgroup and 5.0% in the R-CHOP group) as well as Grade 3 and higher bleeding events (BzR-CAP: 4 patients [1.7%]; R-CHOP: 3 patients [1.2%]).
Seks bortezomib-cyklusser anbefales, men patienter med et respons, som først dokumenteres ved cyklus 6, kan gives yderligere to bortezomib-cyklusser.
Six bortezomib cycles are recommended, although for patients with a response first documented at cycle 6, two additional bortezomib cycles may be given.
Hætteglas inden anbrud 2 år (for Bortezomib Accord 1 mg) 3 år (for Bortezomib Accord 3,5 mg)
2 years (for Bortezomib Accord 1 mg) 3 years (for Bortezomib Accord 3.5 mg)
Tabel 8: Bivirkninger hos patienter med mantle-celle-lymfom, som blev behandlet med BzR-CAP i et klinisk studie
Table 8 Adverse reactions in patients with Mantle cell lymphoma treated with BzR-CAP in a clinical trial
I tilfælde af bortezomib-relateret neuropatisk smerte og/eller perifer neuropati indstilles og/eller modificeres Bortezomib Accord-behandlingen som beskrevet i tabel 1.
For bortezomib-related neuropathic pain and/or peripheral neuropathy, hold and/or modify Bortezomib Accord as outlined in Table 1.
Bortezomib-kombinationsbehandling med pegyleret liposomal doxorubicin (studie DOXILMMY-3001)
Bortezomib combination treatment with pegylated liposomal doxorubicin (study DOXIL-MMY-3001)
Analysen påviste forbedret ORR (CR+PR) (odds-ratio 3,769; 95 % CI 2,045-6,947; p < 0,001), PFS (hazard ratio 0,511; 95 % CI 0,309--0,845; p=0,008), TTP (hazard ratio 0,385; 95 % CI 0,212--0,698; p = 0,001) for bortezomib sammen med dexamethason over bortezomib som monoterapi.
The analysis demonstrated improved ORR (CR+PR) (odds ratio 3.769; 95% CI 2.045-6.947; p < 0.001), PFS (hazard ratio 0.511; 95% CI 0.309-0.845; p=0.008), TTP (hazard ratio 0.385; 95% CI 0.212-0.698; p=0.001) for bortezomib in combination with dexamethasone over bortezomib monotherapy.
Særligt skal du fortælle lægen, hvis du bruger medicin, som indeholder følgende aktive stoffer: - ketoconazol, som bruges til behandling af svampeinfektioner - ritonavir, bruges til behandling af Hiv-infektion - rifampicin, et antibiotikum, som bruges til at behandle bakterie-infektioner - carbamazepin, phenytoin eller phenobarbital til behandling af epilepsi - perikon (Hypericum perforatum), naturmedicin som bruges mod depression eller andre lidelser - tabletter til behandling af sukkersyge (diabetes)
In particular, tell your doctor if you are using medicines containing any of the following active substances: - ketoconazole, used to treat fungal infections - ritonavir, used to treat HIV infection - rifampicin, an antibiotic used to treat bacterial infections - carbamazepine, phenytoin or phenobarbital used to treat epilepsy - St. John's Wort (Hypericum perforatum), used for depression or other conditions - oral antidiabetics
Kun til subkutan eller intravenøs anvendelse.
Subcutaneous or Intravenous use.
Da dialyse kan reducere koncentrationen af bortezomib, bør Bortezomib Accord gives efter dialyse (se pkt.
Since dialysis may reduce bortezomib concentrations, Bortezomib Accord should be administered after the dialysis procedure (see section 5.2).
Demografiske og baseline-sygdomskarakteristika var generelt afbalanceret mellem de to behandlingsarme: Den mediane patientalder var 66 år, 74 % var mænd, 66 % var kaukasere og 32 % asiater, 69 % af patienterne havde et positivt knoglemarvsaspirat og/eller en positiv knoglemarvsbiopsi for MCL, 54 % af patienterne havde en IPI-score (International Prognostic Index) på ≥ 3, og 76 % var i sygdomsstadie IV. Behandlingens varighed (median=17 uger) og varigheden af opfølgningen (median=40 måneder) var sammenlignelige i de to behandlingsarme.
The demographic and baseline disease characteristics were generally well balanced between the two treatment arms: median patient age was 66 years, 74% were male, 66% were Caucasian and 32% Asian, 69% of patients had a positive bone marrow aspirate and/or a positive bone marrow biopsy for MCL, 54% of patients had an International Prognostic Index (IPI) score of ≥ 3, and 76% had Stage IV
Tabel 7: Bivirkninger hos patienter med myelomatose behandlet med bortezomib i kliniske studier samt alle bivirkninger efter markedsføring, uanset indikation
Table 7:Adverse reactions in patients with Multiple Myeloma treated with Bortezomib in clinical trials, and all post-marketing adverse reactions regardless of indication
Nedsat appetit
• Increased appetite
Almindelig Leukopeni*, lymfopeni*
Leukopenia*, Lymphopenia*
Hyperbilirubinæmi*, abnorme proteinanalyser*, vægtstigning, abnorm blodprøve*, forhøjet C-reaktivt protein
Hyperbilirubinaemia*, Protein analyses abnormal*, Weight increased, Blood test abnormal*,C-reactive protein increased
Bortezomib Accord gives intravenøst eller subkutant på dag 1, 4, 8 og 11, fulgt af en ‘hvileperiode' uden behandling.
Bortezomib Accord is given intravenously or subcutaneously on days 1, 4, 8 and 11, followed by a ‘rest period' without treatment.
Responsrate efter 8 cyklusser n (%)
Response Rate at 8 cycles n (%)
• at Bortezomib Accord 3,5 mg kan administreres enten intravenøst eller subkutant, mens Bortezomib Accord 1 mg kun må administreres intravenøst
• Bortezomib Accord 3.5 mg can be administered both intravenously and subcutaneously, while Bortezomib Accord 1 mg can be administered only intravenously
Den mediane OS var 90,7 måneder for BzR-CAP -gruppen sammenlignet med 55,7 måneder for R-CHOP-gruppen (HR = 0,66; p = 0,001).
Median OS was 90.7 months for the BzR-CAP group compared with 55.7 months for the R-CHOP group (HR=0.66; p=0.001).
Der er ikke data, der tyder på, at dosisjustering er nødvendig hos patienter med myelomatose eller mantle-celle-lymfom, der er ældre end 65 år.
There is no evidence to suggest that dose adjustments are necessary in patients over 65 years of age with multiple myeloma or with mental cell lymphona.
Hændelser n (%) Mediana (95 % CI)
Events n (%) Mediana (95% CI)
• rådgivning om intravenøs og subkutan administration, herunder at der bør skiftes mellem injektionssteder ved subkutan anvendelse
• advice on method of administration for both intravenous and subcutaneous use, including the need to rotate injection sites for subcutaneous use
Tabel 9: Forekomst af perifer neuropati under induktionsbehandling efter toksicitet og behandlingsseponering på grund af perifer neuropati
Table 9: Incidence of peripheral neuropathy during induction treatment by toxicity and treatment discontinuation due to peripheral neuropathy
Bortezomib Accord kan forårsage træthed, svimmelhed, besvimelse og uklart/sløret syn.
Bortezomib Accord might cause tiredness, dizziness, fainting, or blurred vision.
54 uger) og blev seponeret før tid ved sygdomsprogression eller uacceptabel toksicitet.
Treatment was administered for a maximum of 9 cycles (approximately 54 weeks) and was discontinued early for disease progression or unacceptable toxicity.
Melphalan og prednison bør begge gives oralt på dag 1, 2, 3 og 4 i den første uge af hver behandlingscyklus med Bortezomib Accord.
Melphalan and prednisone should both be given orally on days 1, 2, 3 and 4 of the first week of each Bortezomib Accord treatment cycle.
som var refraktære over for den seneste behandling, og de, der ikke var refraktære, var den samlede overlevelse signifikant længere, og responsraten var signifikant højere i bortezomib-gruppen.
Both in patients who were refractory to their last prior therapy and those who were not refractory, overall survival was significantly longer and response rate was significantly higher on the bortezomib arm.
Tabel 15: Oversigt over effektanalyser til sammenligning af subkutan og intravenøs administration af bortezomib bortezomib intravenøs gruppe bortezomib subkutan gruppe
Table 15: Summary of efficacy analyses comparing subcutaneous and intravenous administrations of bortezomib bortezomib intravenous arm bortezomib subcutaneous arm
I fase III-studiet med hidtil ubehandlede myelomatosepatienter var den samlede forekomst af herpes zoster-reaktivering større hos patienter behandlet med bortezomib+melphalan+prednison sammenlignet med melphalan+prednison (14 % versus 4 %).
In the Phase III study in patients with previously untreated multiple myeloma, the overall incidence of herpes zoster reactivation was more common in patients treated with bortezomib+melphalan+prednisone compared with melphalan+prednisone (14% versus 4% respectively).
Responsrate efter 4 cyklusser n (%)
Response Rate at 4 cycles n (%)
Absorption Efter intravenøs bolusindgift af en dosis på 1,0 mg/m2 og 1,3 mg/m2 til 11 patienter med myelomatose og kreatininclearance-værdier på mere end 50 ml/min., var de gennemsnitlige maksimale plasmakoncentrationer af bortezomib efter første dosis henholdsvis 57 og 112 ng/ml.
Absorption Following intravenous bolus administration of a 1.0 mg/m2 and 1.3 mg/m2 dose to 11 patients with multiple myeloma and creatinine clearance values greater than 50 ml/min, the mean first-dose maximum plasma concentrations of bortezomib were 57 and 112 ng/ml, respectively.