Thrombopoietic activity of recombinant human interleukin 11 in cancer patients receiving chemotherapy.
Interleukin 11 (IL-11) is a newly identified hematopoietic growth factor that exerts its primary effect on megakaryocyte maturation and platelet production. It has a unique receptor, signaling by which is mediated by the glycoprotein (GP) 130 pathway. IL-11 is synergistic with stem-cell factor (c-kit ligand) in vitro, enhancing proliferation of primitive hematopoietic stem cells, and has been shown to be critical to the process of polyploidization and maturation. In preclinical models, IL-11 was shown to enhance platelet recovery following intensive chemotherapy, and in murine bone-marrow transplant models it accelerates the recovery of all hematopoietic lineages. Nonhuman primate studies have demonstrated a dose-related thrombopoietic effect; however, no myeloid effect has been observed. In clinical phase I trials, subcutaneous IL-11 was well tolerated and induced a dose-related thrombopoietic effect in women with breast cancer. IL-11 at doses of > 25 micrograms/kg per day appeared to reduce the severity of chemotherapy-induced thrombocytopenia. In a randomized phase II trial, IL-11 at 50 micrograms/kg reduced the requirement for platelet transfusions as compared with that in placebotreated controls. IL-11 is an interesting factor; however, further studies are needed to confirm its activity and are in progress.
Gordon
M S
MS
Indiana University Medical Center, Indianapolis 46202-5265, USA.
D000970:Antineoplastic Agents / Q000009:adverse effects; D001943:Breast Neoplasms / Q000188:drug therapy; D002986:Clinical Trials as Topic; D005260:Female; D006410:Hematopoiesis / Q000187:drug effects*; D006801:Humans; D017370:Interleukin-11 / Q000502:physiology / Q000627:therapeutic use*
D000970:Antineoplastic Agents; D017370:Interleukin-11