Drug intelligence / Profile preview

pentoxifylline + chemotherapy

Development stage
Phase 3
Lead developer
Ramón Óscar González-Ramella
Modality
Small Molecules, Recombinant Proteins and Enzymes
Administration
Oral, Intravenous, Intramuscular, Intrathecal
01

Overview

This combination therapy consists of the methylxanthine derivative pentoxifylline administered as an adjunct to a multi-agent induction chemotherapy regimen for the treatment of pediatric acute lymphoblastic leukemia (ALL). Pentoxifylline functions as a non-specific phosphodiesterase inhibitor and a modulator of the IKK/NF-κB signaling pathway; by inhibiting IκB phosphorylation, it prevents the nuclear translocation of NF-κB and subsequently reduces the expression of anti-apoptotic genes. This mechanism is intended to sensitize leukemic blasts to the cytotoxic effects of the standard chemotherapy backbone, which in this specific protocol includes prednisone, vincristine, daunorubicin, L-asparaginase, cyclophosphamide, cytarabine, 6-mercaptopurine, methotrexate, and hydrocortisone. The regimen was evaluated in a Phase 2/3 clinical trial (NCT02451774) led by Dr. Ramón Óscar González-Ramella to determine if the addition of pentoxifylline improves early remission rates and minimal residual disease (MRD) clearance in newly diagnosed pediatric patients.

Other names
Pentoxifylline Plus ChemotherapyPentoxifylline in Pediatric Acute Lymphoblastic Leukemia
02

Targets

GR (Glucocorticoid receptor)IKK complexNF-κBDNADNA polymerase familyTOP2A (DNA topoisomerase II)DHFR (Dihydrofolate reductase)HPRT1 (Hypoxanthine-guanine phosphoribosyltransferase)CHUK (IKKα)PDE (Phosphodiesterase family)TUBB (Tubulin (alpha and beta subunits))

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