Kakamigahara, Japan
Kakamigahara, Japan

Time filter

Source Type

Tsuburaya A.,Yokohama City University | Yoshida K.,Gifu University | Yoshino S.,Yamaguchi University | Takahashi M.,Yokohama Municipal Citizens Hospital | And 14 more authors.
The Lancet Oncology | Year: 2014

Background: The prognosis for locally advanced gastric cancer is poor despite advances in adjuvant chemotherapy. We did the Stomach cancer Adjuvant Multi-Institutional group Trial (SAMIT) to assess the superiority of sequential treatment (paclitaxel then tegafur and uracil [UFT] or paclitaxel then S-1) compared with monotherapy (UFT or S-1) and also the non-inferiority of UFT compared with S-1. Methods: We did this randomised phase 3 trial with a two-by-two factorial design at 230 hospitals in Japan. We enrolled patients aged 20-80 years with T4a or T4b gastric cancer, who had had D2 dissection and a ECOG performance score of 0-1. Patients were randomly assigned to one of four treatment groups with minimisation for tumour size, lymph node metastasis, and study site. Patients received UFT only (267 mg/m2 per day), S-1 only (80 mg/m2 per day) for 14 days, with a 7-day rest period or three courses of intermittent weekly paclitaxel (80 mg/m2) followed by either UFT, or S-1. Treatment lasted 48 weeks in monotherapy groups and 49 weeks in the sequential treatment groups. The primary endpoint was disease-free survival assessed by intention to treat. We assessed whether UFT was non-inferior to S-1 with a non-inferiority margin of 1·33. This trial was registered at UMIN Clinical Trials Registry, number C000000082. Findings: We randomly assigned 1495 patients between Aug 3, 2004, and Sept 29, 2009. 374 patients were assigned to receive UFT alone, 374 to receive S-1 alone, 374 to received paclitaxel then UFT, and 373 to receive paclitaxel then S-1. We included 1433 patients in the primary analysis after at least 3 years of follow-up (359, 364, 355, and 355 in each group respectively). Protocol treatment was completed by 215 (60%) patients in the UFT group, 224 (62%) in the S-1 group, 242 (68%) in the paclitaxel then UFT group, and 250 (70%) in the paclitaxel then S-1 group. 3-year disease-free survival for monotherapy was 54·0% (95% CI 50·2-57·6) and that of sequential treatment was 57·2% (53·4-60·8; hazard ratio [HR] 0·92, 95% CI 0·80-1·07, p=0·273). 3-year disease-free survival for the UFT group was 53·0% (95% CI 49·2-56·6) and that of the S-1 group was 58·2% (54·4-61·8; HR 0·81, 95% CI 0·70-0·93, p=0·0048; pnon-inferiority=0·151). The most common grade 3-4 haematological adverse event was neutropenia (41 [11%] of 359 patients in the UFT group, 48 [13%] of 363 in the S-1 group, 46 [13%] of 355 in the paclitaxel then UFT group, and 83 [23%] of 356 in the paclitaxel then S-1 group). The most common grade 3-4 non-haematological adverse event was anorexia (21 [6%], 24 [7%], seven [2%], and 18 [5%], respectively). Interpretation: Sequential treatment did not improve disease-free survival, and UFT was not non-inferior to S-1 (and S-1 was superior to UFT), therefore S-1 monotherapy should remain the standard treatment for locally advanced gastric cancer in Japan. Funding: Epidemiological and Clinical Research Information Network. © 2014 Elsevier Ltd.


In totale sono stati arruolati in un rapporto 1:1 (59 pazienti trattati con CT-P10 e 62 pazienti trattati con rituximab di riferimento) 121 pazienti affetti da linfoma follicolare acuto per dimostrare la similarità in termini di farmacocinetica tra CT-P10 e rituximab di riferimento, entrambi in combinazione con chemioterapia standard a base di ciclofosfamide, vincristina e prednisone (CVP). I risultati dello studio clinico randomizzato, in doppio cieco e controllato hanno rilevato profili similari in termini di farmacocinetica e farmacodinamica (PD), immunogenicità e sicurezza tra CT-P10 e rituximab di riferimento fino a 12 settimane. 1 Il Dr. Bertrand Coiffier, ricercatore responsabile globale dello studio sulla LFA, responsabile del Dipartimento di ematologia presso gli Hospices Civils de Lyon e docente dell'Università Claude Bernard, di Lione, in Francia, ha dichiarato: " I risultati presentati oggi mostrano profili similari in termini di PK e profili comparabili in termini di cinetica delle cellule B, immunogenicità e sicurezza tra biosimilare rituximab CT-P10 e rituximab di riferimento nei pazienti affetti da LFA, a conferma dei risultati comparabili degli studi clinici sui pazienti affetti da AR. Il programma complessivo offre prove sostanziali e convincenti della similarità tra CT-P10 e rituximab di riferimento. " Si prevede che la disponibilità di biosimilare rituximab CT-P10 per il trattamento dei pazienti affetti da malattie linfoproliferative ridurrà i costi di trattamento, permettendo potenzialmente a più pazienti di iniziare ad assumere rituximab non solo per la fase di induzione, ma anche per quelle di manutenzione e consolidamento". Man Hoon Kim, presidente e CEO di Celltrion Healthcare, ha dichiarato: " Sulla base di tutte le prove raccolte dal nostro programma clinico globale, riteniamo che CT-P10 rappresenti un'alternativa al prodotto di riferimento dal buon rapporto costo-efficacia in grado di migliorare l'accesso dei pazienti e, in ultima istanza, di ridurre il costo dell'utilizzo di rituximab in diverse indicazioni in campo autoimmunitario e oncologico in numerosi paesi del mondo". Christian Buske, professore e direttore medico del Comprehensive Cancer Center di Ulm, in Germania, direttore dell'Institute of Experimental Cancer Research, medico e professore di Medicina presso il Dipartimento medico di medicina Interna III, Divisione di Ematologia/Oncologia, ha dichiarato: " Sulla base dei dati dello studio sulla LFA, in qualità di ematologo e oncologo, accolgo con favore lo sviluppo di nuove opzioni terapeutiche che potrebbero facilitare e ampliare l'accesso a terapie efficaci e convenienti da parte dei pazienti affetti da linfoma. La disponibilità di un biosimilare rituximab può migliorare enormemente l'accesso dei pazienti affetti da disturbi linfoidi maligni a un trattamento a base di un anticorpo diretto contro il CD20 estremamente efficiente". Michinori Ogura, professore e direttore del Dipartimento di ematologia presso il Tokai Central Hospital, in Giappone, ha affermato: " È evidente la similarità tra CT-P10 e rituximab di riferimento in termini di PK, di deplezione delle cellule B, di sicurezza e immunogenicità in 4 cicli terapici. Avendo partecipato in numerosi studi clinici su rituximab, posso affermare che i dati riferiti alla farmacologia clinica e alla sicurezza sono in linea con altri studi a cui ho collaborato in passato. Si prevede quindi che CT-P10 darà risultati simili a rituximab di riferimento nell'ambiente clinico per tutte le indicazioni e le condizioni d'uso. Ovviamente è necessario disporre di dati a lungo termine sull'efficacia e la tossicità". CT-P10 è un rituximab biosimilare candidato. I risultati più importanti del primo studio clinico su CT-P10, uno studio clinico controllato randomizzato di fase 1 rispetto a rituximab di riferimento nei pazienti con AR attiva, sono stati pubblicati di recente e dimostrano che la farmacocinetica (PK) dei due farmaci dopo un unico ciclo di trattamento risultava statisticamente equivalente, e che la loro efficacia, farmacodinamica (PD), immunogenicità e sicurezza erano simili fino alla settimana 245 I dati clinici dello studio di estensione di fase 1 di 72 settimane e un ulteriore studio sul passaggio al prodotto biosimilare sono stati presentati alla conferenza 2015 dell'American College of Rheumatology6 e al congresso annuale 2016 della European Union League Against Rheumatism.4 Sono in corso 3 studi clinici controllati e randomizzati sui pazienti affetti da AR (NCT02149121), LFA (NCT02162771) e da linfoma follicolare a basso carico tumorale (LTBFL) (NCT02260804). È stata dimostrata l'equivalenza in termini di farmacocinetica e di efficacia tra CT-P10 e rituximab di rifermento, con successiva presentazione dei risultati al congresso ACR 2016.3 I linfomi follicolari rappresentano per diffusione il secondo sottotipo dei tumori maligni dei linfonodi nell'Europa occidentale7 e costituiscono un sottotipo del linfoma non-Hodgkin.8 Si tratta di un linfoma a crescita lenta che si sviluppa dai linfociti B (cellule B).10 Si caratterizza per il gonfiore indolore dei linfonodi e per febbre senza ragione apparente, sudori notturni, affaticamento, infezioni e sanguinamento. 10 Al momento della diagnosi molti casi si presentano in stadio già avanzato, ma dal lancio di rituximab la sopravvivenza globale è aumentata fino a superare i 20 anni. 10 Prende il nome di linfoma 'follicolare' a causa della crescita abnorme dei linfociti spesso raggruppati in grumi detti 'follicoli' situati nei linfonodi. 10 Il linfoma follicolare è maggiormente comune nelle persone di oltre 65 anni, ma può colpire pazienti di ogni età. 10 Celltrion Healthcare effettua attività di marketing, vendita e distribuzione dei biofarmaci sviluppati da Celltrion, Inc. a livello mondiale tramite un'estesa rete internazionale che comprende oltre 120 diversi paesi. I prodotti di Celltrion Healthcare sono realizzati a partire da colture cellulari di mammiferi in avanzate strutture progettate e costruite in conformità agli standard cGMP della Food and Drug Administration (FDA) statunitense e agli standard GMP della UE. Per ulteriori informazioni visitare il sito: http://www.celltrionhealthcare.com/ 1 B. Coiffier, et al. Pharmacokinetic and Safety of CT-P10, a Biosimilar Candidate to the Rituximab Reference Product, in Patients with Newly Diagnosed Advanced Stage Follicular Lymphoma (AFL). 58th Annual Meeting and Exposition of the American Society of Hematology 2016; 1807. 2 Suh, CH. et al. Pharmacokinetics and Safety of Three Formulations of Rituximab (CT-P10, US-sourced Innovator Rituximab and EU-sourced Innovator Rituximab) in Patients with Rheumatoid Arthritis: Results from Phase 3 Randomized Controlled Trial over 24 Weeks. American College of Rheumatology/Association of Rheumatology Health Professionals Annual Meeting 2016; 1634. 3 Yoo, DH, et al. Efficacy and Safety of CT-P10, Rituximab Biosimilar Candidate, and Innovator Rituximab in Patients with Rheumatoid Arthritis: Results from Phase 3 Randomized Controlled Trial over 24 Weeks. American College of Rheumatology/Association of Rheumatology Health Professionals Annual Meeting 2016; 1635. 4 Park, W. et al. THU0162 Comparable Time to Retreatment between CT-P10 and Innovator Rituximab up to 2 Years in Patients with Active Rheumatoid Arthritis. Annals of the Rheumatic Diseases. 2016 Jun 1;75(Suppl 2):241-2. 5 Yoo, DH, et al. A multicentre randomised controlled trial to compare the pharmacokinetics, efficacy and safety of CT-P10 and innovator rituximab in patients with rheumatoid arthritis. Annals of the Rheumatic Diseases. 2016;annrheumdis-2016-209540. 6 Yoo, DH, et al. Efficacy and Safety of Rituximab Biosimilar Candidate (CT-P10) and Innovator Rituximab in Patients with Rheumatoid Arthritis: Results from Phase I Randomized Controlled Trial over 72 Weeks. Arthritis & Rheumatology. 2015;Vol 67. 7 Dreyling, M, et al. Newly diagnosed and relapsed follicular lymphoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Annals of Oncology. 2011;22(suppl 6):vi59-vi63. 8 Kohrt HEK & Ugarte A. Follicular Lymphoma: a Guide for Patients. European Society for Medical Oncology. 2014. Available at: https://www.esmo.org/content/download/52236/963497/file/EN-Follicular-Lymphoma-Guide-for-Patients.pdf [ultimo accesso novembre 2016].


PubMed | International Drug Development Institute, Sakai City Hospital, Kanagawa Cancer Center, Osaka General Medical Center and 14 more.
Type: Journal Article | Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology | Year: 2017

LBA4002 Background: Adjuvant chemotherapy with tegafur/uracil (UFT) used to be a tentative Japanese standard treatment and has been replaced by S-1 according to the result of the ACTS-GC trial, although there has been no direct comparison. Paclitaxel (PTX) has been widely used as one of the key drugs for unresectable GC. A randomized phase III trial with a two-by-two factorial design was planned to assess the survival benefit of sequential use of PTX and oral fluorinated pyrimidines (FPs) in comparison with FPs alone, and to compare UFT and S-1.Patients with serosa-invading GC who underwent R0/1 resection with extended (D2) lymph node dissection were randomized to receive either UFT 267mg/mBetween August 2004 and October 2007, 1,495 patients from 232 centers were randomized with the full analysis set of 1,433. Demographics were well balanced among arm A (n=359), B (n=364), C (n=355), and D (n=355); mean age was 64, 86% were PS 0, 68% of tumors were 8 cm or greater and 85% were clinically node positive. Grade 3-4 neutropenia or anorexia occurred in 11% or 6%, 13% or 7%, 13% or 2%, and 23% or 5% for arm A, B, C, and D, respectively. Other % grade 3-4 toxicities were less than 5%. Median follow-up was 1,875 days and 728 events occurred. Difference in DFS between C+D and A+B were not statistically significant (HR=0.92, 95%CI 0.80-1.07, p= 0.273). HR of A+C vs. B+D was 1.23 (95%CI 1.07-1.43) and hence the null hypothesis was not rejected.There was a trend for better DFS for sequential use of PTX followed by FPs. Comparison between the FPs demonstrated that UFT was inferior to S-1. Sequential PTX/S-1 is safe and effective for locally advanced GC in an adjuvant setting.C000000082.


In totaal werden 121 AFL-patiënten ingeschreven in een verhouding van 1:1 (59 patiënten die CT-P10 en 62 patiënten die het referentieproduct rituximab gebruikten) om de farmacokinetische similariteit tussen CT-P10 en het referentieproduct rituximab aan te tonen. Beide middelen werden toegediend in combinatie met standaard chemotherapie van cyclofosfamide, vincristine en prednison (CVP). De resultaten van het gerandomiseerde, dubbelblinde, gecontroleerde onderzoek duidden op gelijkwaardige farmacokinetiek en vergelijkbare farmacodynamiek, immunogeniciteit en veiligheidsprofiel van CT-P10 in vergelijking met het referentieproduct rituximab over een periode van maximaal 12 weken.1 Dit bewijs van similariteit is consistent met de klinische ervaring met CT-P10 en met de gegevens bij patiënten met reumatoïde artritis (RA), waarbij een duidelijke similariteit werd vastgesteld in farmacokinetiek, farmacodynamiek, werkzaamheid, veiligheid en immunogeniciteit. Het werd gepresenteerd tijdens de jaarlijkse bijeenkomst van het American College of Rheumatology (ACR) van 2016 en het jaarlijkse Europese reumatologiecongres van EULAR (European League Against Rheumatism).2,3,4 Dr. Bertrand Coiffier, de algemene hoofdonderzoeker van het AFL-onderzoek, hoofd van de afdeling hematologie van het Hospices Civils de Lyon en professor aan de Université Claude Bernard, Lyon, Frankrijk, merkte op: “ De vandaag gepresenteerde resultaten tonen gelijkwaardige farmacokinetiek en vergelijkbare B-cel kinetiek, immunogeniciteit en veiligheidsprofielen tussen rituximab biosimilar CT-P10 en het referentieproduct rituximab bij patiënten met AFL. Dit is in lijn met vergelijkbare resultaten in klinische onderzoeken bij patiënten met RA. Het algemene programma biedt aanzienlijk en overtuigend bewijs van similariteit van CT-P10 en het referentieproduct rituximab. Man Hoon Kim, President en CEO van Celltrion Healthcare, stelde: “ Op basis van alle bewijzen die we hebben verzameld tijdens ons wereldwijde klinische programma, geloven we dat CT-P10 een kosteneffectief alternatief is voor het referentieproduct. Het kan de toegankelijkheid voor patiënten verhogen en uiteindelijk leiden tot verlaging van de kosten van het gebruik van rituximab voor auto-immune en oncologische indicaties in veel landen verspreid over de hele wereld.” Michinori Ogura, professor, directeur van de afdeling hematologie van het Tokai Central Hospital in Japan, zei: " Similariteit tussen CT-P10 en het referentieproduct rituximab qua farmacokinetiek, afbraak van B-cellen, veiligheid en immunogeniciteit werd aangetoond tijdens 4 behandelingscycli. Ik ben betrokken geweest bij vele klinische onderzoeken met rituximab. De resultaten in termen van klinische farmacologie en veiligheidsgegevens zijn consistent met andere onderzoeken waaraan ik in het verleden heb meegewerkt. Daarom zullen de prestaties van CT-P10 in de klinische praktijk naar verwachting vergelijkbaar zijn met die van het referentieproduct rituximab binnen de verschillende indicaties en gebruiksomstandigheden. Uiteraard bestaat er nog behoefte aan gegevens over de werkzaamheid en toxiciteit op de lange termijn.” CT-P10 is een rituximab biosimilar kandidaat. De belangrijkste resultaten van het eerste klinische onderzoek naar CT-P10 – een fase 1 RCT in vergelijking met het referentieproduct rituximab bij patiënten met actieve RA – werden onlangs gepubliceerd en lieten zien dat de farmacokinetiek van de twee geneesmiddelen na één behandelingskuur statistisch equivalent was, en dat de werkzaamheid, farmacodynamiek, immunogeniciteit en veiligheid vergelijkbaar waren tot aan week 24.5 De klinische gegevens van een fase 1 vervolgonderzoek van 72 weken en een aanvullend wisselonderzoek van 1 jaar werden gepresenteerd tijdens de bijeenkomst van het American College of Rheumatology van 20156 en het jaarlijkse congres van de European League Against Rheumatism in 2016.4 Drie fase 3 RCT-onderzoeken bij patiënten met RA (NCT02149121), AFL (NCT02162771) en folliculaire lymfoom met lage tumorlast (LTBFL) (NCT02260804) lopen nog. Gelijkwaardige farmacokinetiek en werkzaamheid van CT-P10 en het referentieproduct rituximab werden aangetoond en gepresenteerd op ACR 2016.3 Folliculaire lymfoom is het op een na meest frequente subtype van kwaadaardige tumoren aan de lymfklieren in West-Europa7 en een subtype of NHL.8 Het is een langzaam groeiende lymfoom die ontstaat uit B-lymfocyten (B-cellen).10 Het wordt gekenmerkt door pijnloze opzwelling van de lymfklieren, koorts zonder duidelijke oorzaak, overmatig nachtelijk zweten, vermoeidheid, infecties en bloeding. 10 In de meeste gevallen wordt de aandoening pas in een gevorderd stadium vastgesteld, maar sinds de komst van rituximab is de algemene overleving toegenomen tot meer dan 20 jaar. 10 Het wordt ‘folliculaire’ lymfoom genoemd omdat de afwijkende lymfocyten zich vaak in de lymfklieren verzamelen in clusters die ‘follikels’ worden genoemd. 10 Folliculaire lymfoom komt vaker voor bij personen van 65 jaar en ouder, maar kan zich op elke leeftijd voordoen. 10 Celltrion Healthcare verzorgt de wereldwijde marketing, verkoop en distributie van biologische geneesmiddelen ontwikkeld door Celltrion, Inc. door middel van een uitgebreid wereldwijd netwerk dat meer dan 120 verschillende landen bestrijkt. De producten van Celltrion Healthcare worden gefabriceerd in hypermoderne faciliteiten voor het kweken van zoogdiercellen, ontworpen en gebouwd in overeenstemming met de cGMP-richtlijnen van de Amerikaanse Food and Drug Administration (FDA) en de GMP-richtlijnen van de EU. Meer informatie is te vinden op: http://www.celltrionhealthcare.com/ 1 B. Coiffier, et al. Pharmacokinetic and Safety of CT-P10, a Biosimilar Candidate to the Rituximab Reference Product, in Patients with Newly Diagnosed Advanced Stage Follicular Lymphoma (AFL). 58th Annual Meeting and Exposition of the American Society of Hematology 2016; 1807. 2 Suh, CH. et al. Pharmacokinetics and Safety of Three Formulations of Rituximab (CT-P10, US-sourced Innovator Rituximab and EU-sourced Innovator Rituximab) in Patients with Rheumatoid Arthritis: Results from Phase 3 Randomized Controlled Trial over 24 Weeks. American College of Rheumatology/Association of Rheumatology Health Professionals Annual Meeting 2016; 1634. 3 Yoo, DH, et al. Efficacy and Safety of CT-P10, Rituximab Biosimilar Candidate, and Innovator Rituximab in Patients with Rheumatoid Arthritis: Results from Phase 3 Randomized Controlled Trial over 24 Weeks. American College of Rheumatology/Association of Rheumatology Health Professionals Annual Meeting 2016; 1635. 4 Park, W. et al. THU0162 Comparable Time to Retreatment between CT-P10 and Innovator Rituximab up to 2 Years in Patients with Active Rheumatoid Arthritis. Annals of the Rheumatic Diseases. 2016 Jun 1;75(Suppl 2):241-2. 5 Yoo, DH, et al. A multicentre randomised controlled trial to compare the pharmacokinetics, efficacy and safety of CT-P10 and innovator rituximab in patients with rheumatoid arthritis. Annals of the Rheumatic Diseases. 2016;annrheumdis-2016-209540. 6 Yoo, DH, et al. Efficacy and Safety of Rituximab Biosimilar Candidate (CT-P10) and Innovator Rituximab in Patients with Rheumatoid Arthritis: Results from Phase I Randomized Controlled Trial over 72 Weeks. Arthritis & Rheumatology. 2015;Vol 67. 7 Dreyling, M, et al. Newly diagnosed and relapsed follicular lymphoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Annals of Oncology. 2011;22(suppl 6):vi59-vi63. 8 Kohrt HEK & Ugarte A. Follicular Lymphoma: a Guide for Patients. European Society for Medical Oncology. 2014. Beschikbaar op: https://www.esmo.org/content/download/52236/963497/file/EN-Follicular-Lymphoma-Guide-for-Patients.pdf [geraadpleegd in november 2016]. Deze bekendmaking is officieel geldend in de originele brontaal. Vertalingen zijn slechts als leeshulp bedoeld en moeten worden vergeleken met de tekst in de brontaal, welke als enige rechtsgeldig is.


Au total, 121 patients souffrant de LFA ont été recrutés selon un ratio de 1:1 (59 patients pour le CT-P10 et 62 patients pour le rituximab de référence) en vue de démontrer la similarité, en termes de PC, du CT-P10 par rapport au rituximab de référence, chacun administré conjointement à une chimiothérapie standard composée de cyclophosphamide, de vincristine et de prednisone (CVP). Les résultats de l’étude contrôlée, randomisée et en double aveugle montrent une PC équivalente et des profils pharmacodynamique (PD), d’immunogénicité et d’innocuité du CT-P10 similaires à ceux du rituximab de référence jusqu’à 12 semaines. 1 Les preuves de similarité s’appuyant sur l’expérience clinique du CT-P10 ainsi que sur les données de patients atteints de polyarthrite rhumatoïde (PR), qui montrent une similarité incontestable en matière de PC, de PD, d’efficacité, d’innocuité et d’immunogénicité, ont été présentées au congrès annuel 2016 de l’American College of Rheumatology (ACR) et au congrès européen annuel de rhumatologie (EULAR).2,3,4 Le Dr Bertrand Coiffier, le principal investigateur mondial de l’étude sur le LFA, responsable du département d’hématologie aux Hospices civils de Lyon et professeur à l’Université Claude Bernard, à Lyon, en France, a déclaré : « Les résultats présentés aujourd’hui montrent une PC similaire et des profils cinétique, d’immunogénicité et d’innocuité pour les cellules B comparables entre le biosimilaire du rituximab CT-P10 et le rituximab de référence chez les patients atteints de LFA, confirmant les résultats comparables des études cliniques effectuées chez les patients atteints de PR. Le programme global fournit des preuves substantielles et convaincantes de la similarité entre le CT-P10 et le rituximab de référence. Man Hoon Kim, président et DG de Celltrion Healthcare, a déclaré : « Sur la base de l’ensemble des preuves collectées dans notre programme clinique mondial, nous considérons que le CT-P10 est une alternative économique au produit de référence. Il est susceptible d’améliorer l’accès des patients et au final de réduire le coût de l’utilisation du rituximab dans les indications auto-immunes et d’oncologie dans de nombreux pays à travers les monde. » Christian Buske, professeur et directeur médical – Comprehensive Cancer Center Ulm, Allemagne, Institut de recherche expérimentale sur le cancer, et médecin référant et professeur de médecine au département médical pour la médecine interne III, Hématologie/Oncologie, a affirmé : « Sur la base des données de l’étude sur le LFA, je me réjouis, en tant qu’hématologue/oncologue, du développement de nouvelles options thérapeutiques susceptibles de faciliter et d’élargir l’accès des patients atteints d’un lymphome à des thérapies efficaces et abordables. La disponibilité d’un biosimilaire du rituximab peut améliorer énormément l’accès des patients atteints de troubles lymphoïdes malins à un traitement par anticorps anti-CD20 très efficace. » Michinori Ogura, professeur et directeur du département d’hématologie au Tokai Central Hospital, au Japon, a déclaré : « La similarité en termes de PC, de déplétion des cellules B, d’innocuité et d’immunogénicité durant 4 cycles de traitement a été prouvée entre le CT-P10 et le rituximab de référence. Ayant été impliqué dans de nombreuses études cliniques sur le rituximab, les résultats en termes de pharmacologie clinique et de données de sécurité sont cohérents avec d’autres études auxquelles j’ai participé par le passé. Par conséquent, le CT-P10 devrait offrir des performances similaires au rituximab de référence dans le cadre clinique pour différentes indications et conditions d’utilisation. Bien sûr, nous avons encore besoin de résultats sur l’efficacité et la toxicité à long terme. » Le CT-P10 est un candidat biosimilaire du rituximab. Les principaux résultats de la première étude clinique du CT-P10 – un essai randomisé contrôlé (ERC) de phase 1 comparant par rapport au rituximab de référence chez les patients atteints de PR active – ont été récemment publiés et ont démontré que la pharmacocinétique (PC) des deux médicaments après une seule unité de traitement était statistiquement équivalente, et que leur efficacité, pharmacodynamique (PD), immunogénicité et innocuité étaient similaires jusqu’en semaine 24.5 Les données cliniques de l’étude de prolongation de phase 1, d’une durée de 72 semaines, et d’une étude de changement supplémentaire, d’une durée d’un an, ont été présentées au congrès 2015 de l’American College of Rheumatology6 et au congrès annuel de la Ligue Européenne contre le Rhumatisme en 2016.4 Trois ERC de phase 3 sur des patients atteints de PR (NCT02149121), de LFA (NCT02162771) et de lymphome folliculaire à faible charge tumorale (NCT02260804) sont en cours. Une pharmacocinétique et une efficacité équivalentes ont été démontrées entre le CT-P10 et le rituximab de référence, elles ont été présentées au congrès 2016 de l’ACR.3 Les lymphomes folliculaires sont le deuxième sous-type le plus fréquent de malignités lymphoïdes nodales en Europe de l’Ouest7 et sont un sous-type de LNH.8 Il s’agit d’un lymphome à croissance lente qui se développe à partir des lymphocytes B (cellules B).10 Il se caractérise par un gonflement indolore des ganglions lymphatiques, de la fièvre sans raison apparente, des sueurs nocturnes importantes, de la fatigue, des infections et des saignements. 10 La plupart des cas sont à un stade avancé lors du diagnostic mais, depuis l’arrivée du rituximab, la survie globale a augmenté et peut dépasser les 20 ans. 10 On l’appelle lymphome « folliculaire » car les lymphocytes anormaux s’agglutinent souvent dans les ganglions lymphatiques en amas connus sous le nom de « follicules ». 10 Le lymphome folliculaire est plus courant chez les personnes de plus de 65 ans, mais il peut survenir chez des individus de tout âge. 10 Celltrion Healthcare se charge de la commercialisation, la vente et la distribution de médicaments biologiques mis au point par Celltrion, Inc. à travers un vaste réseau mondial couvrant plus de 120 pays. Les produits de Celltrion Healthcare sont fabriqués dans des installations de pointe destinées à la culture de cellules de mammifères, conçues et fabriquées en conformité avec les directives cGMP de la FDA américaine et les directives de l'UE en matière de bonnes pratiques de fabrication. Pour de plus amples informations, veuillez consulter le site http://www.celltrionhealthcare.com/ 1 B. Coiffier, et al. Pharmacokinetic and Safety of CT-P10, a Biosimilar Candidate to the Rituximab Reference Product, in Patients with Newly Diagnosed Advanced Stage Follicular Lymphoma (AFL). 58th Annual Meeting and Exposition of the American Society of Hematology 2016; 1807. 2 Suh, CH. et al. Pharmacokinetics and Safety of Three Formulations of Rituximab (CT-P10, US-sourced Innovator Rituximab and EU-sourced Innovator Rituximab) in Patients with Rheumatoid Arthritis: Results from Phase 3 Randomized Controlled Trial over 24 Weeks. American College of Rheumatology/Association of Rheumatology Health Professionals Annual Meeting 2016; 1634. 3 Yoo, DH, et al. Efficacy and Safety of CT-P10, Rituximab Biosimilar Candidate, and Innovator Rituximab in Patients with Rheumatoid Arthritis: Results from Phase 3 Randomized Controlled Trial over 24 Weeks. American College of Rheumatology/Association of Rheumatology Health Professionals Annual Meeting 2016; 1635. 4 Park, W. et al. THU0162 Comparable Time to Retreatment between CT-P10 and Innovator Rituximab up to 2 Years in Patients with Active Rheumatoid Arthritis. Annals of the Rheumatic Diseases. 2016 Jun 1;75(Suppl 2):241-2. 5 Yoo, DH, et al. A multicentre randomised controlled trial to compare the pharmacokinetics, efficacy and safety of CT-P10 and innovator rituximab in patients with rheumatoid arthritis. Annals of the Rheumatic Diseases. 2016;annrheumdis-2016-209540. 6 Yoo, DH, et al. Efficacy and Safety of Rituximab Biosimilar Candidate (CT-P10) and Innovator Rituximab in Patients with Rheumatoid Arthritis: Results from Phase I Randomized Controlled Trial over 72 Weeks. Arthritis & Rheumatology. 2015;Vol 67. 7 Dreyling, M, et al. Newly diagnosed and relapsed follicular lymphoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Annals of Oncology. 2011;22(suppl 6):vi59-vi63.


SAN DIEGO--(BUSINESS WIRE)--New data presented at the 2016 American Society of Hematology (ASH) Annual Meeting demonstrate that CT-P10 (biosimilar rituximab candidate) and reference rituximab are equivalent in terms of pharmacokinetics (PK) in patients with advanced follicular lymphoma (AFL), a form of non-Hodgkin lymphoma. 1 A total of 121 AFL patients were enrolled in a 1:1 ratio (59 patients on CT-P10 and 62 patients on reference rituximab) to demonstrate PK similarity of CT-P10 to reference rituximab, each given in combination with standard chemotherapy of cyclophosphamide, vincristine, and prednisone (CVP). The results from the randomized, double-blind, controlled study found equivalent PK and similar pharmacodynamics (PD), immunogenicity and safety profiles of CT-P10 to those of reference rituximab for up to 12 weeks. 1 This evidence of similarity builds on clinical experience of CT-P10 along with the data in patients with rheumatoid arthritis (RA), which shows compelling similarity in PK, PD, efficacy, safety and immunogenicity and was presented at the 2016 American College of Rheumatology (ACR) Annual Meeting and the Annual European Congress of Rheumatology (EULAR).2,3,4 Dr. Bertrand Coiffier, the global principle investigator of the AFL study, Head of the Department of Hematology at Hospices Civils de Lyon and Professor at the University Claude Bernard, Lyon, France, said: “ The results presented today show similar PK and comparable B cell kinetics, immunogenicity and safety profiles between CT-P10 biosimilar rituximab and reference rituximab in patients with AFL, confirming comparable results in clinical studies in patients with RA. The overall program provides substantial and convincing evidence for similarity between CT-P10 and reference rituximab. “ The availability of CT-P10 biosimilar rituximab for treatment of patients with lymphoproliferative disorders is expected to reduce costs of treatment, potentially enabling more patients to initiate rituximab treatment not only through induction but also maintenance and consolidation phases of treatment.” Man Hoon Kim, President and CEO of Celltrion Healthcare, said: “ Based on the totality of evidence collected from our global clinical programme, we believe that CT-P10 is a cost-effective alternative to the reference product. It could improve patient access and ultimately reduce the cost of rituximab use across autoimmune and oncology indications in many countries throughout the world.” Christian Buske, Professor, Medical Director – Comprehensive Cancer Center Ulm, Germany, Institute of Experimental Cancer Research and Attending Physician and Professor of Medicine at the Medical Department for Internal Medicine III, Hematology/Oncology, said: “ Based on the data from AFL, I, as a haematologist/oncologist, welcome the development of new therapeutic options that could facilitate and broaden access of lymphoma patients to efficacious and affordable therapies. The availability of a biosimilar rituximab can tremendously improve access of patients with malignant lymphoid disorders to highly efficient anti-CD20 antibody treatment.” Michinori Ogura, Professor, Director of the Department of Hematology at Tokai Central Hospital, Japan, said:" The similarity in PK, B-cell depletion, safety and immunogenicity through 4 cycles of therapy were shown between CT-P10 and reference rituximab. Having being involved in numerous clinical studies with rituximab, the results in terms of clinical pharmacology and safety data are consistent with other studies I have been involved in the past. Therefore, CT-P10 is anticipated to perform similarly to the reference rituximab in the clinical setting across indications and conditions of use. Of course, it remains to have long-term data of efficacy and toxicity.” Rituximab is a CD20-directed cytolytic antibody indicated for the treatment of patients with non-Hodgkin’s lymphoma (NHL), chronic lymphocytic leukemia (CLL), rheumatoid arthritis (RA), granulomatosis with polyangiitis, and microscopic polyangiitis. CT-P10 is a rituximab biosimilar candidate. The primary results of the first clinical study of CT-P10 – a phase 1 RCT versus reference rituximab in patients with active RA – were recently published and demonstrated the pharmacokinetics (PK) of the two drugs after a single course of treatment were statistically equivalent, and that their efficacy, pharmacodynamics (PD), immunogenicity, and safety were similar up to week 24.5 The clinical data of phase 1 72-week extension study and an additional 1-year switching study were presented at the American College of Rheumatology’s 2015 meeting6 and the annual European Union League Against Rheumatism congress in 2016.4 Three phase 3 RCT studies in patients with RA (NCT02149121), AFL (NCT02162771) and low-tumor-burden follicular lymphoma (LTBFL) (NCT02260804) are ongoing. Equivalent pharmacokinetics and efficacy were demonstrated between CT-P10 and reference rituximab and presented in ACR 2016.3 Follicular lymphomas are the second most frequent subtype of nodal lymphoid malignancies in Western Europe7 and is a subtype of NHL.8 It is a slow-growing lymphoma that develops from B lymphocytes (B cells).10 It is characterized by painless swelling of the lymph nodes, fever for no apparent reason, drenching night sweats, fatigue, infections and bleeding. 10 Most cases are advanced at the time of diagnosis but since the advent of rituximab, overall survival has increased to in excess of 20 years. 10 It is called ‘follicular’ lymphoma because the abnormal lymphocytes often collect in lymph nodes in clumps that are known as ‘follicles’. 10 Follicular lymphoma is more common in people aged over 65, but it can occur in people of any age. 10 Celltrion Healthcare conducts the worldwide marketing, sales and distribution of biological medicines developed by Celltrion, Inc. through an extensive global network that spans more than 120 different countries. Celltrion Healthcare’s products are manufactured at state-of-the-art mammalian cell culture facilities, designed and built to comply with the US Food and Drug Administration (FDA) cGMP guidelines and the EU GMP guidelines. For more information please visit: http://www.celltrionhealthcare.com/ 1 B. Coiffier, et al. Pharmacokinetic and Safety of CT-P10, a Biosimilar Candidate to the Rituximab Reference Product, in Patients with Newly Diagnosed Advanced Stage Follicular Lymphoma (AFL). 58th Annual Meeting and Exposition of the American Society of Hematology 2016; 1807. 2 Suh, CH. et al. Pharmacokinetics and Safety of Three Formulations of Rituximab (CT-P10, US-sourced Innovator Rituximab and EU-sourced Innovator Rituximab) in Patients with Rheumatoid Arthritis: Results from Phase 3 Randomized Controlled Trial over 24 Weeks. American College of Rheumatology/Association of Rheumatology Health Professionals Annual Meeting 2016; 1634. 3 Yoo, DH, et al. Efficacy and Safety of CT-P10, Rituximab Biosimilar Candidate, and Innovator Rituximab in Patients with Rheumatoid Arthritis: Results from Phase 3 Randomized Controlled Trial over 24 Weeks. American College of Rheumatology/Association of Rheumatology Health Professionals Annual Meeting 2016; 1635. 4 Park, W. et al. THU0162 Comparable Time to Retreatment between CT-P10 and Innovator Rituximab up to 2 Years in Patients with Active Rheumatoid Arthritis. Annals of the Rheumatic Diseases. 2016 Jun 1;75(Suppl 2):241-2. 5 Yoo, DH, et al. A multicentre randomised controlled trial to compare the pharmacokinetics, efficacy and safety of CT-P10 and innovator rituximab in patients with rheumatoid arthritis. Annals of the Rheumatic Diseases. 2016;annrheumdis-2016-209540. 6 Yoo, DH, et al. Efficacy and Safety of Rituximab Biosimilar Candidate (CT-P10) and Innovator Rituximab in Patients with Rheumatoid Arthritis: Results from Phase I Randomized Controlled Trial over 72 Weeks. Arthritis & Rheumatology. 2015;Vol 67. 7 Dreyling, M, et al. Newly diagnosed and relapsed follicular lymphoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Annals of Oncology. 2011;22(suppl 6):vi59-vi63. 8 Kohrt HEK & Ugarte A. Follicular Lymphoma: a Guide for Patients. European Society for Medical Oncology. 2014. Available at: https://www.esmo.org/content/download/52236/963497/file/EN-Follicular-Lymphoma-Guide-for-Patients.pdf [accessed November 2016].


Dr. Bertrand Coiffier, der global verantwortliche Prüfer der FFL-Studie, Leiter der Abteilung für Hämatologie bei Hospices Civils de Lyon und Professor an der University Claude Bernard in Lyon (Frankreich), erläuterte: „ Die heute vorgestellten Ergebnisse zeigen eine ähnliche PK und vergleichbare B-Zellen-Kinetik-, Immunogenitäts- und Sicherheitsprofile für das Rituximab-Biosimilar CT-P10 und das Referenzprodukt Rituximab bei Patienten mit FFL, was vergleichbare Ergebnisse klinischer Studien mit RA-Patienten bestätigt. Insgesamt liefert das klinische Programm eine wesentliche und überzeugende Bestätigung der Ähnlichkeit von CT-P10 und dem Referenzarzneimittel Rituximab.“ Michinori Ogura, Professor, Direktor der Abteilung für Hämatologie am Tokai Central Hospital, Japan, erläuterte: „ Die Ähnlichkeit bei PK, Abbau von B-Zellen, Sicherheit und Immunogenität im Verlauf von vier Therapiezyklen wurde für CT-P10 und das Referenzprodukt Rituximab nachgewiesen. Ich habe bereits an zahlreichen klinischen Studien mit Rituximab mitgewirkt, und die Ergebnisse mit Blick auf die klinischen Pharmakologie- und Sicherheitsdaten stehen im Einklang mit anderen Studien, an denen ich in der Vergangenheit beteiligt war. Daher wird davon ausgegangen, dass CT-P10 in der klinischen Umgebung indikationsübergreifend sowie unter verschiedenen Anwendungsbedingungen ähnlich wie das Referenzarzneimittel Rituximab wirken wird. Natürlich werden noch Langzeitdaten im Hinblick auf die Wirksamkeit und Toxizität benötigt.“ CT-P10 ist ein Rituximab-Biosimilar-Kandidat. Die primären Ergebnisse der ersten klinischen Studie – einer randomisierten kontrollierten Studie der Phase 1 – zu CT-P10 im Vergleich zu dem Referenzprodukt Rituximab bei Patienten mit aktiver RA wurden vor kurzem veröffentlicht. Sie zeigen, dass die Pharmakokinetik (PK) der beiden Arzneimittel nach einer einzigen Behandlung statistisch äquivalent war und ihre Wirksamkeit, Pharmakodynamik (PD), Immunogenität und Sicherheit bis zur 24. Woche ähnlich waren.5 Die klinischen Daten der 72-wöchigen Phase-1-Anschlussstudie und der zusätzlichen einjährigen Umstellungsstudie wurden 2015 auf der Konferenz des American College of Rheumatology (ACR)6 und 2016 auf der Jahrestagung der European Union League Against Rheumatism vorgestellt.4 Derzeit befinden sich drei randomisierte kontrollierte Studien der Phase 3 zur Evaluierung von Patienten mit RA (NCT02149121), FFL (NCT02162771) und follikulärem Lymphom mit geringer Tumorbelastung (LTBFL) (NCT02260804) in der Durchführung. Äquivalenz in Pharmakokinetik und Wirksamkeit wurde für CT-P10 und das Referenzprodukt Rituximab demonstriert und Daten diesbezüglich wurden auf der ACR-Tagung 2016 präsentiert.3 Follikuläre Lymphome sind der zweithäufigste Subtyp nodaler Lymphome in Westeuropa7 und zudem ein Subtyp des NHL.8 Es handelt sich dabei um langsam wachsende Lymphome, die aus B-Lymphozyten (B-Zellen) entstehen.10 Sie sind durch eine schmerzlose Schwellung der Lymphknoten, scheinbar grundloses Fieber, nächtliche Schweißausbrüche, Müdigkeit, Infektionen und Blutungen gekennzeichnet. 10 Die meisten Fälle sind zum Zeitpunkt der Diagnose fortgeschritten, doch mit der Verfügbarkeit von Rituximab hat sich das Gesamtüberleben auf über 20 Jahre verlängert. 10 Die Bezeichnung „follikuläres Lymphom“ rührt daher, dass die abnormalen Lymphozyten sich oftmals in Lymphknoten in Klumpen ansammeln, die „Follikel“ genannt werden. 10 Das follikuläre Lymphom ist bei Menschen über 65 häufiger, kann jedoch bei Personen jedes Alters auftreten. 10 1 Coiffier, B. et al.: Pharmacokinetic and Safety of CT-P10, a Biosimilar Candidate to the Rituximab Reference Product, in Patients with Newly Diagnosed Advanced Stage Follicular Lymphoma (AFL). 58th Annual Meeting and Exposition of the American Society of Hematology 2016; 1807. 2 Suh, C. H. et al.: Pharmacokinetics and Safety of Three Formulations of Rituximab (CT-P10, US-sourced Innovator Rituximab and EU-sourced Innovator Rituximab) in Patients with Rheumatoid Arthritis: Results from Phase 3 Randomized Controlled Trial over 24 Weeks. American College of Rheumatology/Association of Rheumatology Health Professionals Annual Meeting 2016; 1634. 3 Yoo, D. H. et al.: Efficacy and Safety of CT-P10, Rituximab Biosimilar Candidate, and Innovator Rituximab in Patients with Rheumatoid Arthritis: Results from Phase 3 Randomized Controlled Trial over 24 Weeks. American College of Rheumatology/Association of Rheumatology Health Professionals Annual Meeting 2016; 1635. 4 Park, W. et al.: THU0162 Comparable Time to Retreatment between CT-P10 and Innovator Rituximab up to 2 Years in Patients with Active Rheumatoid Arthritis. Annals of the Rheumatic Diseases. 2016 Jun 1; 75 (Suppl 2): 241–2. 5 Yoo, D. H. et al.: A multicentre randomised controlled trial to compare the pharmacokinetics, efficacy and safety of CT-P10 and innovator rituximab in patients with rheumatoid arthritis. Annals of the Rheumatic Diseases. 2016; annrheumdis-2016-209540. 6 Yoo, D. H. et al.: Efficacy and Safety of Rituximab Biosimilar Candidate (CT-P10) and Innovator Rituximab in Patients with Rheumatoid Arthritis: Results from Phase I Randomized Controlled Trial over 72 Weeks. Arthritis & Rheumatology. 2015; Vol 67. 7 Dreyling, M. et al.: Newly diagnosed and relapsed follicular lymphoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Annals of Oncology. 2011; 22 (suppl 6): vi59–vi63.


Hayashi D.,Nagoya University | Hayashi D.,Tokai Central Hospital | Ohshima S.,Nagoya University | Ohshima S.,Tsushima City Hospital | And 10 more authors.
Journal of the American College of Cardiology | Year: 2013

Objectives: This study investigated whether the technitium-99m sestamibi (MIBI) washout rate (WR) would predict mitochondrial damage and myocardial dysfunction in patients with dilated cardiomyopathy (DCM). Background: Myocardial mitochondrial damage reduces adenosine triphosphate production, resulting in myocardial dysfunction. Increased myocardial 99mTc-MIBI washout is reportedly caused by mitochondrial dysfunction. Methods: Twenty DCM patients (New York Heart Association functional class I-III) underwent myocardial 99mTc-MIBI scintigraphy and cardiac catheterization. Myocardial MIBI uptake was quantified as an early and delayed heart-to-mediastinum ratio, and WR was calculated. Maximum first derivative of left ventricular (LV) pressure (LV dP/dtmax) (an index of myocardial contractility) and LV pressure half-time (T1/2) (an index of myocardial relaxation) were calculated by the left ventricular pressure curve at baseline and during dobutamine infusion (15 μg/kg/min at maximum). Endomyocardial biopsy specimens were obtained for quantitative mRNA analysis and electron microscopy. The patients were divided into two groups as follows: 1) group A of 10 patients showing a WR ≤24.3% (median value) and 2) group B of 10 patients showing a WR >24.3%. Results: WR was significantly correlated with the percentage changes in LV dP/dtmax (%LV dP/dtmax) (r: -0.59; p = 0.01) and T1/2 (r: -0.57; p = 0.03) from baseline to peak dobutamine stress. The %LV dP/dtmax was significantly greater in group B than in group A. The abundance of mRNAs for mitochondrial electron transport-related enzymes was more significantly reduced in group B than in group A. Electron microscopy revealed significant correlations between WR and the severity of mitochondrial damage (r: 0.88; p = 0.048) and glycogen accumulation (r: 0.90; p = 0.044). Conclusions: Increased 99mTc-MIBI washout may predict mitochondrial dysfunction and the impairment of myocardial contractile and relaxation reserves during dobutamine stress in DCM patients. © 2013 American College of Cardiology Foundation.


Maeda H.,Cancer Treatment Center | Kobayashi M.,Cancer Treatment Center | Sakamoto J.,Tokai Central Hospital
World Journal of Gastroenterology | Year: 2015

Malignant ascites affects approximately 10% of patients with gastric cancer (gc), and poses significant difficulties for both patients and clinicians. In addition to the dismal general condition of affected patients and the diversity of associated complications such as jaundice and ileus, problems in assessing scattered tumors have hampered the expansion of clinical trials for this condition. However, the accumulation of reported studies is starting to indicate that the weak response to treatment in gc patients with malignant ascites is more relevant to their poor prognosis rather than to the ascites volume at diagnosis. Therefore, precise assessment of initial state of ascites, repetitive evaluation of treatment efficacy, selection of suitable treatment, and swift transition to other treatment options as needed are paramount to maximizing patient benefit. Accurately determining ascites volume is the crucial first step in clinically treating a patient with malignant ascites. Ultrasonography is commonly used to identify the existence of ascites, and several methods have been proposed to estimate ascites volume. Reportedly, the sum of the depth of ascites at five points (named five-point method) on three panels of computed tomography images is well correlated to the actual ascites volume and/or abdominal girth. This method is already suited to repetitive assessment due to its convenience compared to the conventional volume rendering method. Meanwhile, a new concept, Clinical Benefit Response in gc (CBR-GC), was recently introduced to measure the efficacy of chemotherapy for malignant ascites of gc. CBR-GC is a simple and reliable patient-oriented evaluation system based on changes in performance status and ascites, and is expected to become an important clinical endpoint in future clinical trials. The principal of treatment for gc patients with ascites is palliation and prevention of ascites-related symptoms. The treatment options are various, including a standard treatment based on the available guidelines, cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (HIPEC), laparoscopic HIPEC alone, intravenous chemotherapy, intraperitoneal chemotherapy, and molecular targeting therapy. Although each treatment option is valid, further research is imperative to establish the optimal choice for each patient. © 2015 Baishideng Publishing Group Inc. All rights reserved.


Ozaki S.,Tokushima Prefectural Central Hospital | Shimizu K.,Tokai Central Hospital
BioMed Research International | Year: 2014

High-dose melphalan (200 mg/m2) as conditioning regimen followed by autologous stem cell transplantation (ASCT) rescue has been established as a standard treatment for patients with multiple myeloma (MM) younger than 65 years of age. However, the role of ASCT in elderly patients older than 65 years remains controversial in the era of novel agents such as thalidomide, bortezomib, and lenalidomide. The efficacy and feasibility of ASCT have been shown in elderly patients by reducing the dose of melphalan to 100-140 mg/m 2. Although the clinical benefit of reduced-intensity ASCT in elderly patients has not been clearly established in comparison with that of novel agent-based induction therapy, recent studies have demonstrated that sequential strategies of novel agent-based induction therapy and reduced-intensity ASCT followed by consolidation/maintenance with novel agents translate into better outcome in the management of elderly patients. Thus, ASCT could also be a mainstay in the initial treatment of elderly MM patients, and its indication should be evaluated based on performance status and the presence of complications and/or comorbidities of each elderly patient with MM. © 2014 Shuji Ozaki and Kazuyuki Shimizu.

Loading Tokai Central Hospital collaborators
Loading Tokai Central Hospital collaborators