Interleukin-3 (IL-3) is a
glycoprotein produced primarily by activated T-lymphocytes. As a hematopoietic
growth factor it affects the proliferation, maturation, and survival of progenitor cells of the myeloid, erythroid, and megakaryocyte lineages. Initial studies in
cancer patients with normal bone marrow using
IL-3 doses of > 5 micrograms/kg daily produced a doubling of the neutrophil count within 2-3 days and that of platelet counts by days 10-12. Phase I-II clinical trials have examined the response to
IL-3 in various clinical states, and ongoing phase III studies are currently assessing the clinical relevance. In the treatment of relapsed
lymphoma, small-cell lung cancer, and breast and
ovarian cancer,
IL-3 at doses of 5-10 micrograms/kg daily given mainly subcutaneously for 5-10 days has been shown to maintain
chemotherapy schedules while preserving adequate granulocyte and platelet numbers in the peripheral blood. At these doses, side effects were uncommon. The translation of these observations into clinical phase III studies has been disappointing, with no clear-cut clinical advantage being observed in the treated group. This reflects the relative lack of myelosuppression seen with most current regimens for solid
tumors. The role of combined treatment with
IL-3 in association with
granulocyte colony-stimulating factor or
granulocyte-macrophage colony-stimulating factor after cytotoxic treatment has yet to be established. However, it has been shown that they may act synergistically, resulting in significantly higher numbers of progenitor cells in the peripheral blood than when either is used alone. Combinations with
IL-6 are also under study, as is the use of "cocktails" for ex vivo expansion of progenitors. This latter approach would allow single, small collections to be used for multiple infusions of progenitors and could support significant dose-intensification regimens by relieving myelosuppression. It is clear that the place of these newer
cytokines in current treatment remains to be clarified.