Interferon-alfa-based treatment of chronic myeloid leukemia and implications of signal transduction inhibition.
The cytokine interferon-alfa (IFN-alpha) has substantial activity in chronic myeloid leukemia (CML) and is the nontransplant standard of care for chronic-phase disease. When used as front-line therapy, IFN-alpha induces a state of tumor dormancy and delays progression to advanced phase. Unfortunately, IFN-alpha is associated with substantial toxicity at therapeutic doses. The introduction of pegylated IFN-alpha (PEG-IFN-alpha), a modified form of the protein that permits weekly administration, may alleviate some of the problems observed with IFN-alpha. Combination regimens of IFN-alpha with other drugs such as cytarabine (Ara-C) appear to enhance efficacy and are currently under investigation. The tyrosine kinase inhibitor imatinib mesylate (Gleevec, Novartis Pharmaceuticals Corp, East Hanover, NJ) (formerly STI571) also is efficacious in chronic-phase CML, with a low toxicity profile. However, its potential to cure CML remains unknown even though it achieves frequent cytogenetic responses. To enhance treatment outcome, a combination of IFN-alpha and imatinib mesylate therapies is proposed. Low-dose IFN-alpha may be given after imatinib mesylate-induced remission as a specific immune stimulant to consolidate the remission. Recent data showing a possible additive effect of imatinib mesylate and IFN-alpha suggest that concurrent use of these agents may also be more effective than single use, particularly in advanced stages of CML where imatinib mesylate has activity but resistance develops.
Talpaz
M
M
Division of Medicine, Department of Bioimmunotherapy, M.D. Anderson Cancer Center, Houston, TX 77030, USA.
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001549:Benzamides; D006801:Humans; D000068877:Imatinib Mesylate; D016898:Interferon-alpha / Q000493:pharmacokinetics / Q000627:therapeutic use* / Q000633:toxicity; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy*; D010879:Piperazines / Q000627:therapeutic use; D011743:Pyrimidines / Q000627:therapeutic use; D015398:Signal Transduction / Q000187:drug effects
D001549:Benzamides; D016898:Interferon-alpha; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate