TY - JOUR
T1 - Management of Chemotherapy-Induced Thrombocytopenia
T2 - Current Status of Thrombopoietic Agents
AU - Vadhan-Raj, Saroj
N1 - Copyright:
Copyright 2009 Elsevier B.V., All rights reserved.
PY - 2009/1
Y1 - 2009/1
N2 - Myelosuppression, one of the most common toxicities of chemotherapy, results in varying degree of cytopenias. While neutropenia and anemia have been reduced with the currently approved hematopoietic growth factors, thrombocytopenia remains a significant clinical problem with an unmet medical need. Although platelet transfusions can provide a temporary solution, they do not address the underlying cause of thrombocytopenia. Management of chemotherapy-associated thrombocytopenia often involves dose reductions or treatment delays. Thrombocytopenia can also affect quality of life and significantly increase healthcare costs. With the introduction of several novel antineoplastic agents with an increased propensity to cause thrombocytopenia, a further increase in the incidence of thrombocytopenia can be expected. Despite the extensive efforts in the clinical development of thrombopoietic agents in the past decade, recombinant interleukin-11 (IL-11) is the only agent currently approved by the US Food and Drug Administration for thrombocytopenia induced by chemotherapy. The use of this agent is limited due to its narrow therapeutic index. While promising biologic activity was observed with recombinant thrombopoietins (TPOs) in nonmyeloablative clinical settings, further clinical development was halted due to evidence of neutralizing antibodies to pegylated recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF). Recently, a number of novel TPO receptor agonists have been developed with promising clinical activity and a lesser potential for immunogenicity. Several of these second-generation platelet-stimulating agents are currently in clinical development, including peptide (romiplostim, formerly AMG-531) and nonpeptide (eltrombopag and AKR501) mimetics. The clinical trials of romiplostim and eltrombopag are currently ongoing to optimize their dose and schedule in ameliorating chemotherapy-induced thrombocytopenia.
AB - Myelosuppression, one of the most common toxicities of chemotherapy, results in varying degree of cytopenias. While neutropenia and anemia have been reduced with the currently approved hematopoietic growth factors, thrombocytopenia remains a significant clinical problem with an unmet medical need. Although platelet transfusions can provide a temporary solution, they do not address the underlying cause of thrombocytopenia. Management of chemotherapy-associated thrombocytopenia often involves dose reductions or treatment delays. Thrombocytopenia can also affect quality of life and significantly increase healthcare costs. With the introduction of several novel antineoplastic agents with an increased propensity to cause thrombocytopenia, a further increase in the incidence of thrombocytopenia can be expected. Despite the extensive efforts in the clinical development of thrombopoietic agents in the past decade, recombinant interleukin-11 (IL-11) is the only agent currently approved by the US Food and Drug Administration for thrombocytopenia induced by chemotherapy. The use of this agent is limited due to its narrow therapeutic index. While promising biologic activity was observed with recombinant thrombopoietins (TPOs) in nonmyeloablative clinical settings, further clinical development was halted due to evidence of neutralizing antibodies to pegylated recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF). Recently, a number of novel TPO receptor agonists have been developed with promising clinical activity and a lesser potential for immunogenicity. Several of these second-generation platelet-stimulating agents are currently in clinical development, including peptide (romiplostim, formerly AMG-531) and nonpeptide (eltrombopag and AKR501) mimetics. The clinical trials of romiplostim and eltrombopag are currently ongoing to optimize their dose and schedule in ameliorating chemotherapy-induced thrombocytopenia.
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U2 - 10.1053/j.seminhematol.2008.12.007
DO - 10.1053/j.seminhematol.2008.12.007
M3 - Article
C2 - 19245931
AN - SCOPUS:60549096096
SN - 0037-1963
VL - 46
SP - S26-S32
JO - Seminars in hematology
JF - Seminars in hematology
IS - SUPPL. 2
ER -