CSFs in combination with cytosine arabinoside, an inhibitor of DNA synthesis: potential strategies for the treatment of myeloid disorders.
CSFs may be useful in improving the clinical effectiveness of cytosine arabinoside (ara-C). In vitro studies have indicated that GM-CSF may be capable of specifically increasing the sensitivity of leukemic cells to this agent. Other studies have indicated that IL-3 may enhance the ability of ara-C to kill leukemic cells by cytokinetic and pharmacologic mechanisms. While the effects of GM-CSF and IL-3 on ara-C-induced differentiation appear limited, the combination of ara-C and leukemia inhibitory factor (LIF) may appear to be useful in overcoming the block in differentiation characteristic of leukemic myeloblasts. On the basis of in vitro studies, clinical trials with ara-C are underway that are examining the usefulness of GM-CSF and IL-3 in cell cycle recruitment of leukemic myeloblasts. These cytokines are also under study in supportive therapy of ara-C-induced myelosuppression. While certain results appear promising, further controlled studies are needed to determine the role of CSFs in improving ara-C therapy.
Brach
M
M
Laboratory of Clinical Pharmacology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115.
Stone
R
R
Kufe
D
D
D002454:Cell Differentiation / Q000187:drug effects; D003115:Colony-Stimulating Factors / Q000008:administration & dosage*; D003561:Cytarabine / Q000008:administration & dosage*; D004273:DNA, Neoplasm / Q000096:biosynthesis; D004357:Drug Synergism; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000008:administration & dosage; D006801:Humans; D066298:In Vitro Techniques; D007377:Interleukin-3 / Q000008:administration & dosage; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000378:metabolism / Q000628:therapy
D003115:Colony-Stimulating Factors; D004273:DNA, Neoplasm; D007377:Interleukin-3; D003561:Cytarabine; D016178:Granulocyte-Macrophage Colony-Stimulating Factor