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vincristine + mercaptopurine + L-asparaginase + doxorubicin + cyclophosphamide + cytarabine + dexamethasone + intrathecal methotrexate

Development stage
Phase 2
Lead developer
Eli Lilly
Modality
Classical Binding Small Molecules → Small Molecules, Covalent Small Molecules → Small Molecules, Nucleic Acid-Directed Small Molecules → Small Molecules
Administration
Intravenous, Oral, Intramuscular, Subcutaneous, Intrathecal
01

Overview

The combination "vincristine + mercaptopurine + L-asparaginase + doxorubicin + cyclophosphamide + cytarabine + dexamethasone + intrathecal methotrexate" represents an intensive chemotherapy regimen used primarily in the treatment of acute lymphoblastic leukemia (ALL). This multi-drug approach is designed to target cancer cells through various mechanisms while minimizing the development of drug resistance. This combination is typically administered in phases during ALL treatment, including induction, consolidation, and maintenance phases. The drugs work synergistically to eliminate leukemia cells and prevent their regrowth. Some components like intrathecal methotrexate specifically target the central nervous system to prevent or treat leukemia spread to that area. Clinical studies have shown that intensive regimens using these drugs can achieve complete remission rates of approximately 78-80% in adult ALL patients, with some protocols demonstrating improved survival rates compared to less intensive approaches[1][2]. For example, one study showed that an intensive therapy protocol increased the probability of remaining in complete remission at 80 months from 20% to 34%, with median survival improving from 14 months to 34 months[2]. The combination does carry significant toxicity risks, with common adverse reactions including nausea, vomiting, mucositis, neutropenia, diarrhea, and constipation, ranging from mild to moderate in severity[5]. However, most adverse reactions do not leave permanent sequelae in patients.

Other names
Delayed Intensification regimenDI phase chemotherapyvincristine + mercaptopurine + L-asparaginase + doxorubicin + cyclophosphamide + cytarabine + dexamethasone + intrathecal methotrexate
02

Targets

DNAPOLA1 (DNA polymerase alpha)DHFR (Dihydrofolate reductase)GR (Glucocorticoid receptor)HPRT1 (Hypoxanthine-guanine phosphoribosyltransferase)RAC1 (Rac family small GTPase 1)TOP2B (DNA topoisomerase II beta)TOP2A (DNA topoisomerase II)TUBB (Tubulin (alpha and beta subunits))Microtubule

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