Clinical experience with recombinant human thrombopoietin in chemotherapy-induced thrombocytopenia.
Since the identification and cloning of c-Mpl ligand, two forms of recombinant human thrombopoietin have undergone clinical development. Both the full-length molecule, known as rhTPO, and the truncated version of the molecule, known as pegylated recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF), have been evaluated in phase I/II clinical trials in cancer patients receiving myelosuppressive chemotherapy. Early clinical trials with PEG-rHuMGDF in cancer patients demonstrated its clinical safety and platelet-stimulating activity. However, the development of neutralizing antibodies and clinically significant thrombocytopenia in some patients and normal donors who received PEG-rHuMGDF have led to discontinuation of clinical trials with this molecule in the United States. Clinical experience with rhTPO so far indicates that this full-length glycosylated molecule is remarkably well tolerated and has a favorable safety profile. In these studies, rhTPO exhibited dose-dependent increases in circulating platelet counts and bone marrow megakaryocytes before chemotherapy. In addition, there was an increase in the frequency and proliferation of bone marrow progenitor cells and mobilization of progenitors into the peripheral blood. Early results also showed that rhTPO can attenuate chemotherapy-induced severe thrombocytopenia and reduce the need for platelet transfusions. However, in this setting, the optimal schedule of rhTPO administration may depend on the length of the regimen and anticipated timing of the platelet nadir. These initial results indicate that rhTPO is a safe and potentially useful agent in the prevention and management of chemotherapy-induced thrombocytopenia. Results of larger randomized clinical trials will determine the therapeutic potential of this novel growth factor in various clinical settings.
Vadhan-Raj
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Bioimmunotherapy Department, University of Texas MD Anderson Cancer Center, Houston 77030-4095, USA.
D000970:Antineoplastic Agents / Q000009:adverse effects*; D002986:Clinical Trials as Topic; D006031:Glycosylation; D006801:Humans; D010976:Platelet Count / Q000187:drug effects; D011092:Polyethylene Glycols / Q000378:metabolism; D011993:Recombinant Fusion Proteins; D011994:Recombinant Proteins / Q000627:therapeutic use; D013921:Thrombocytopenia / Q000139:chemically induced / Q000188:drug therapy*; D013926:Thrombopoietin / Q000627:therapeutic use*
D000970:Antineoplastic Agents; D011993:Recombinant Fusion Proteins; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D013926:Thrombopoietin