Drug intelligence / Profile preview

cladribine + cytarabine + etoposide + mitoxantrone

Development stage
Unknown
Lead developer
Children's Oncology Group
Modality
Small Molecules
Administration
Intravenous
01

Overview

A combination chemotherapy regimen consisting of cladribine, cytarabine, etoposide, and mitoxantrone, specifically developed and evaluated by the Children's Oncology Group (COG) for the treatment of pediatric and young adult patients with relapsed or refractory acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS). This regimen, notably studied in the Phase II trial AAML0021, utilizes the synergistic biochemical interaction between nucleoside analogs and topoisomerase II inhibitors. Cladribine is included to enhance the intracellular accumulation of cytarabine triphosphate (Ara-CTP), the active metabolite of cytarabine, thereby increasing its antileukemic activity. Mitoxantrone and etoposide provide potent DNA intercalation and topoisomerase II inhibition, leading to extensive double-strand DNA breaks and apoptosis in resistant leukemic blasts. This intensive salvage therapy is intended to induce complete remission in high-risk patients who have failed initial induction or experienced early relapse.

Other names
mitoxantrone-Children's Oncology Group-acute myeloid leukemia-myelodysplastic syndromeCLAM-Emitoxantrone hydrochloridecladribine + ara-C + etoposide + mitoxantrone
02

Targets

RNR (Ribonucleotide reductase)DNA polymerase familyDNATOP2A (DNA topoisomerase II)

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