daunorubicin
Sources réglementaires consultées
Indications approuvées
- Leucémies aiguës dans les protocoles d’induction et de consolidation autorisés. Il ne s’agit pas de daunorubicine/cytarabine liposomale.
Contre-indications
Absolues
- Hypersensibilité ; infections sévères ; myélosuppression persistante ; insuffisance hépatique ou rénale sévère ; insuffisance cardiaque ou cardiomyopathie sévère ; allaitement. Cela inclut Child-Pugh C, DFG <10 ml/min ou créatinine >7,9 mg/dl, cardiopathie sévère ou arythmie significative et atteinte du maximum cumulatif.
Mises en garde cliniques
- Surveiller la numération avant chaque cycle et pendant le nadir. Ne pas administrer hors protocole oncologique spécialisé ; la myélosuppression peut provoquer une infection ou une hémorragie mortelle. — CIMA/AEMPS, ficha técnica 46427
- Calculer l’exposition cumulée antérieure aux anthracyclines et évaluer la fonction ventriculaire avant et pendant le traitement. Cardiomyopathie et insuffisance cardiaque peuvent survenir pendant le traitement ou des années plus tard. — CIMA/AEMPS, ficha técnica 46427
- Administrer uniquement par une voie intraveineuse perméable. Arrêter immédiatement en cas de suspicion d’extravasation : c’est un vésicant pouvant provoquer une nécrose sévère. — CIMA/AEMPS, ficha técnica 46427
- Surveiller numération, fonctions rénale/hépatique, moelle, ECG/FEVG et syndrome de lyse tumorale. Éviter les vaccins vivants. — CIMA/AEMPS, ficha técnica 46427
- Il existe un risque de leucémie secondaire, généralement avec une latence de 1 à 3 ans, surtout avec d’autres antinéoplasiques lésant l’ADN ou une radiothérapie. La radiothérapie médiastinale peut augmenter la cardiotoxicité, et la daunorubicine peut provoquer des réactions locales de rappel de rayonnement. — CIMA/AEMPS, ficha técnica 46427
Interactions médicamenteuses
- SévèreAutres médicaments cardiotoxiques ou myélosuppresseurs
Mécanisme: Ils peuvent augmenter cardiotoxicité et myélosuppression.
Recommandation: Utiliser uniquement les associations du protocole et surveiller cœur et numération.
CIMA/AEMPS, ficha técnica 46427
- SévèreMéthotrexate, hépatotoxiques, aspirine et vaccins vivants
Mécanisme: Ils peuvent augmenter hépatotoxicité, hémorragie ou infection vaccinale.
Recommandation: Éviter vaccins vivants et aspirine en thrombopénie ; surveiller étroitement avec méthotrexate ou autres hépatotoxiques.
CIMA/AEMPS, ficha técnica 46427
Grossesse et allaitement
La grossesse et l’allaitement sont contre-indiqués. Les femmes doivent utiliser une contraception pendant le traitement et au moins 27 semaines après ; les hommes pendant le traitement et au moins 14 semaines après.
Bibliographie récente (PubMed)
The first 5 decades of research in acute myeloid leukemia (AML) were dominated by the cytarabine plus anthracyclines backbone, with advances in strategies including allogeneic hematopoietic stem cell transplantation, high-dose cytarabine, supportive care measures, and targeted therapies for the subset of patients with acute promyelocytic leukemia. Since 2017, a turning point in AML research, 12 agents have received regulatory approval for AML in the United States: venetoclax (BCL2 inhibitor); gemtuzumab ozogamicin (CD33 antibody-drug conjugate); midostaurin, gilteritinib, and quizartinib (fms-like tyrosine kinase 3 inhibitors); ivosidenib, olutasidenib, and enasidenib (isocitrate dehydrogenase 1 and 2 inhibitors); oral azacitidine (a partially absorbable formulation); CPX351 (liposomal encapsulation of cytarabine:daunorubicin at a molar ratio of 5:1); glasdegib (hedgehog inhibitor); and recently revumenib (menin inhibitor; approved November 2024). Oral decitabine-cedazuridine, which is approved as a bioequivalent alternative to parenteral hypomethylating agents in myelodysplastic syndrome, can be used for the same purpose in AML. Menin inhibitors, CD123 antibody-drug conjugates, and other antibodies targeting CD123, CD33, and other surface markers are showing promising results. Herein, the authors review the frontline and later line therapies in AML and discuss important research directions.
Patients with acute myeloid leukaemia (AML) positive for internal tandem duplication (ITD) mutations of FLT3 have poor outcomes. Quizartinib, an oral, highly potent, selective, type 2 FLT3 inhibitor, plus chemotherapy showed antitumour activity with an acceptable safety profile in patients with FLT3-ITD-positive newly diagnosed AML. The aim of the study was to compare the effect of quizartinib versus placebo on overall survival in patients with FLT3-ITD-positive newly diagnosed AML aged 18-75 years. We conducted a randomised, double-blind, placebo-controlled, phase 3 trial comparing quizartinib and placebo in combination with chemotherapy in induction and consolidation, followed by quizartinib or placebo single-agent continuation, in patients with FLT3-ITD-positive newly diagnosed AML at 193 hospitals and clinics in 26 countries in Europe; North America; and Asia, Australia, and South America. Patients aged 18-75 years were eligible. Patients were randomly assigned (1:1) to the quizartinib group or the placebo group by an independent biostatistician through an interactive web and voice response system, stratified by region, age, and white blood cell count at diagnosis. Patients, investigators, funders, and contract research organisations were masked to treatments assigned. Induction therapy comprised a standard 7 + 3 induction regimen of cytarabine 100 mg/m2 per day (or 200 mg/m2 per day allowed if institutional or local standard) by continuous intravenous infusion from day 1 to day 7 and anthracycline (daunorubicin 60 mg/m2 per day or idarubicin 12 mg/m2 per day) by intravenous infusion on days 1, 2, and 3, then quizartinib 40 mg orally or placebo once per day, starting on day 8, for 14 days. Patients with complete remission or complete remission with incomplete neutrophil or platelet recovery received standard consolidation with high-dose cytarabine plus quizartinib (40 mg per day orally) or placebo, allogeneic haematopoietic cell transplantation (allo-HCT), or bo
The understanding of the molecular pathobiology of acute myeloid leukemia (AML) has spurred the identification of therapeutic targets and the development of corresponding novel targeted therapies. Since 2017, twelve agents have been approved for the treatment of AML subsets: the BCL2 inhibitor venetoclax; the CD33 antibody drug conjugate gemtuzumab ozogamicin; three FLT3 inhibitors (midostaurin, gilteritinib, quizartinib); three IDH inhibitors (ivosidenib and olutasidenib targeting IDH1 mutations; enasidenib targeting IDH2 mutations); two oral hypomethylating agents (oral poorly absorbable azacitidine; fully absorbable decitabine-cedazuridine [latter approved as an alternative to parenteral hypomethylating agents in myelodysplastic syndrome and chronic myelomonocytic leukemia but commonly used in AML]); and CPX-351 (encapsulated liposomal 5:1 molar ratio of cytarabine and daunorubicin), and glasdegib (hedgehog inhibitor). Other targeted therapies (menin inhibitors, CD123 antibody-drug conjugates) are showing promising results. To achieve optimal results in such a rare and heterogeneous entity as AML requires expertise, familiarity with this rare cancer, and the access to, and delivery of disparate therapies under rigorous supportive care conditions. In this review, we update the standard-of-care and investigational therapies and outline promising current and future research directions. Most sources consider breastfeeding to be contraindicated during maternal antineoplastic drug therapy, especially anthracyclines such as daunorubicin.[1] It might be possible to breastfeed safely during intermittent therapy with an appropriate period of breastfeeding abstinence. Based on the 27-hour half-life of the active metabolite daunorubicinol a minimum of 6 days would be required before resuming nursing. Chemotherapy may adversely affect the normal microbiome and chemical makeup of breastmilk.[2] Women who receive chemotherapy during pregnancy are more likely to have difficulty
Therapy-related acute myeloid leukemia (t-AML), defined as AML arising from prior cytotoxic, radiation, or immunosuppressive therapy for an unrelated disease, accounts for 7 %-8 % of AML cases and primarily occurs in elderly patients. t-AML is associated with an increased probability of adverse cytogenetics and shortened survival compared with de novo AML. Factors predicting poorer prognosis in t-AML include older age, unfavorable karyotype, presence of certain mutations, poor performance status, and poor bone marrow reserve. Few clinical studies have focused specifically on patients with t-AML, and the choice of induction therapy for t-AML is thus typically based on subset analyses of larger studies or on extrapolation. In patients deemed fit, t-AML treatment can involve CPX-351 (liposomal daunorubicin and cytarabine) or conventional chemotherapy, ideally followed by hematopoietic cell transplantation. Patients who are not candidates for intensive therapy may benefit from lower-intensity therapies. Additional agents and combination regimens are being evaluated in clinical studies.