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Idarubicin + Methotrexate + Filgrastim + Cytarabine

Development stage
Unknown
Lead developer
Pfizer
Modality
Nucleic Acid-Directed Small Molecules → Small Molecules, Covalent Small Molecules → Small Molecules, Classical Binding Small Molecules → Small Molecules
Administration
Intravenous, Subcutaneous
01

Overview

The combination of idarubicin, methotrexate, filgrastim, and cytarabine is a chemotherapy regimen used primarily for treating hematological malignancies, particularly in primary central nervous system lymphoma (PCNSL) and acute myeloid leukemia (AML). This combination leverages multiple mechanisms of action: idarubicin is an anthracycline that intercalates with DNA and inhibits topoisomerase II; methotrexate is an antimetabolite that inhibits dihydrofolate reductase; cytarabine is a nucleoside analog that interferes with DNA synthesis; and filgrastim (G-CSF) is added to stimulate neutrophil production and reduce the duration of neutropenia following chemotherapy[1][2][3]. ## Clinical Applications The combination has shown efficacy in several contexts: 1. **Primary Central Nervous System Lymphoma (PCNSL)**: Studies have demonstrated that methotrexate plus idarubicin improves outcomes compared to methotrexate alone, with higher complete response rates (62.50% vs 42.31%) and better progression-free survival (18.35 months vs 8.45 months)[1]. 2. **Acute Myeloid Leukemia (AML)**: Various combinations of these agents are used in induction and consolidation therapy for AML[7]. 3. **Relapsed/Refractory Acute Lymphoblastic Leukemia (ALL)**: Similar combinations have shown efficacy in treating refractory or early relapse ALL and T-cell lymphoblastic non-Hodgkin's lymphoma (NHL)[2]. ## Administration and Dosing The regimen typically involves: - Methotrexate: Often given at high doses (3 g/m²) - Idarubicin: Usually administered as a single infusion (e.g., 40 mg/m²) - Cytarabine: May be given at high doses (3 g/m²/day for 5 days) - Filgrastim: Typically started after chemotherapy until neutrophil recovery[2][6] ## Safety Profile The addition of filgrastim significantly reduces: - Duration of neutropenia (by approximately 5 days) - Duration of fever - Need for parenteral antibiotics - Length of hospitalization - Requirement for systemic antifungal therapy[6] Common side effects include myelosuppression, infections, and other typical chemotherapy-related toxicities. However, the addition of filgrastim helps mitigate some of these adverse effects by accelerating neutrophil recovery[6].

Other names
Chemotherapy regimen combining idarubicin, methotrexate, filgrastim, and cytarabine
02

Targets

DNACSF3R (Granulocyte colony-stimulating factor receptor)DNA polymerase familyDHFR (Dihydrofolate reductase)TOP2A (DNA topoisomerase II)

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