Systematic Review of the Efficacy and Safety of Alternative Azacitidine Regimens in Myelodysplastic Syndrome
Notice bibliographique
Résumé
Abstract Background 5-Azacitidine has been shown in randomized clinical trials to have a significant degree of efficacy with good tolerability in myelodysplastic syndrome (MDS) patients with intermediate/high risk according to the International Prognostic Scoring System (IPSS) score. The dosing regimen that was approved based on the AZA-001 randomized clinical trial was a 7-day 75mg/m2 regimen (7-0-0). However based on practical considerations, many centers use alternative regimens such as a 5-day 75mg/m2 (5-0-0) or 5-day followed by weekend break, followed by an additional 2-day (5-2-2) regimen at 75mg/m2. No randomized controlled trial has been done directly comparing all the different dosing regimens to ensure they attain the same efficacy as demonstrated for the 7-0-0 one. The objective of this study was to evaluate the efficacy and tolerability of the different dosing regimens of azacitidine in patients with MDS, chronic myelomonocytic leukemia (CMML) and acute myeloid leukemia with < 30% blasts (AML). Methods A systematic review of the literature was conducted using the MEDLINE and EMBASE databases. Eligible studies were randomized controlled trials, observational prospective and observational retrospective studies of various azacitidine regimens in MDS, CMML, or AML. Key extracted data included number of patients, azacitidine dosing, and clinical outcomes as per the International Working Group (IWG). The primary clinical outcome was Objective Response Rate (ORR) defined as the sum of complete response (CR) + partial response (PR) + hematological improvement (HI) by the IWG 2006 response criteria. The primary tolerability outcome was the proportion of patients requiring azacitidine dose adjustment as part of their treatment course. We conducted a meta-analysis of simple proportions using a random effects model with weights defined according to Laird and Mosteller. Comparisons between groups were not attempted due to the heterogeneity of study designs. Results Of the 2183 studies identified, 39 articles and 37 abstracts including 4868 patients were included in the analysis. There was a small number of studies directly comparing the different azacitidine regimens. Based on a total of two studies there was no statistical difference in terms of ORR between the 5-0-0 & 7-0-0 regimens. Based on a total of two studies, there was no statistical difference in terms of ORR between the 5-0-0 & 5-2-2 dosing regimens. The pooled proportion of ORR was 45% (variance 1.3%) for the 7-0-0 dosing regimen, 38% (variance 1.5%) for the 5-0-0 regimen, and 47% (variance 3.7%) for the 5-2-2 regimen. The 7-0-0 regimen resulted in 17% of patients requiring dose adjustment (variance 10%), the 5-0-0 regimen resulted in 34% of patients requiring dose adjustment (variance 4.3%), and the 5-2-2 regimen resulted in 25% of patients requiring dose adjustment (variance 15%). Conclusions There are few studies directly comparing the different dosing regimens of azacitidine in MDS, CMML, and AML in terms of their efficacy. Based on those studies that do, there is no statistically significant difference in terms of the ORR between the 5-0-0 & 7-0-0 treatments, and the 5-0-0 & 5-2-2 treatments. Pooled estimates for the ORR show similar results for the 3 dosing regimens evaluated, but indirect comparisons between groups were not conducted due to heterogeneity in the designs. Further studies directly comparing the azacitidine dosing regimens in MDS, CMML, and AML are required. Disclosures No relevant conflicts of interest to declare.
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
Comment cette classification a été obtenuedéplier
Prédiction machine sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Le volet Gemma est une étiquette directe du modèle pour chaque travail de la base, lue sur la notice réduite au titre. Le volet Codex est un classifieur appris des 10 348 étiquettes directes de Codex et calibré sur les taux pondérés de l'échantillon; les champs sans appui suffisant ne portent aucun appel Codex. Le mode candidate est l'union des deux volets; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont pas des étiquettes humaines.
Scores du classifieur distillé par catégorie (deux têtes)
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,008 | 0,028 |
| Méta-épidémiologie (sens strict) | 0,001 | 0,001 |
| Méta-épidémiologie (sens large) | 0,011 | 0,006 |
| Bibliométrie | 0,011 | 0,011 |
| Études des sciences et des technologies | 0,001 | 0,001 |
| Communication savante | 0,002 | 0,001 |
| Science ouverte | 0,002 | 0,001 |
| Intégrité de la recherche | 0,001 | 0,001 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,005 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule source (Gemma direct ou Codex distillé), pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».