Drug intelligence / Profile preview

homoharringtonine + cytarabine + granulocyte-colony stimulating factor

Development stage
Phase 3
Lead developer
Teva Pharmaceutical Industries
Modality
Small Molecules, Recombinant Proteins and Enzymes
Administration
Intravenous, Subcutaneous
01

Overview

The combination of homoharringtonine, cytarabine, and granulocyte-colony stimulating factor (G-CSF), commonly referred to as the HAG regimen, is a multi-agent chemotherapy protocol primarily used for the treatment of acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS), especially in relapsed/refractory or elderly patients. - **Homoharringtonine** is a plant alkaloid that inhibits protein synthesis by binding to the A-site cleft of ribosomes, leading to apoptosis in leukemic cells. - **Cytarabine** is an antimetabolite that interferes with DNA synthesis during the S-phase of cell division. - **Granulocyte-colony stimulating factor (G-CSF)** acts as a priming agent; it mobilizes leukemic blasts into active cell cycle phases (S-phase for cytarabine sensitivity and G1 phase for homoharringtonine sensitivity), thereby enhancing chemosensitivity and reducing drug resistance. G-CSF also downregulates CXCR4 expression on myeloid cells via upregulation of growth factor independence 1 (Gfi-1) and decreases CXCL12 expression in bone marrow niches[3]. This regimen has demonstrated efficacy with complete remission rates around 50–62% in AML patients—including those who are elderly or have relapsed/refractory disease—and shows improved tolerability compared to intensive chemotherapy regimens[2][3][1]. The most common adverse effect is myelosuppression; non-hematologic toxicity tends to be mild[1][2].

Other names
HAGHHT + Ara-C + G-CSF
02

Targets

DNA polymerase familyCSF3R (Granulocyte colony-stimulating factor receptor)Ribosome

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