title: Romiplostim promotes platelet recovery in a mouse model of multicycle chemotherapy-induced thrombocytopenia.
abstract: Chemotherapy-induced thrombocytopenia can lead to chemotherapy treatment delays or dose reductions. The ability of romiplostim, a thrombopoietin (TPO) mimetic, to promote platelet recovery in a mouse model of multicycle chemotherapy/radiation therapy (CRT)-induced thrombocytopenia was examined. In humans, an inverse relationship between platelet counts and endogenous TPO (eTPO) concentration exists. In a CRT mouse model, eTPO was not elevated during the first 5 days after CRT treatment (the "eTPO gap"), then increased to a peak 10 days after each CRT treatment in an inverse relationship to platelet counts seen in humans. To bridge the eTPO gap, mice were treated with 10-1,000 μg/kg of romiplostim on day 0, 1, or 2 after CRT. In some mice, the romiplostim dose was approximately divided over 3 days. Platelet recovery occurred faster with romiplostim in most conditions tested. Romiplostim doses of ≥100 μg/kg given on day 0 significantly lessened the platelet nadir. Fractionating the dose over 3 days did not appear to confer a large advantage. These data may provide a rationale for clinical studies of romiplostim in chemotherapy-induced thrombocytopenia.
authors.affiliation: Oncology Research Department, Amgen Inc., Thousand Oaks, CA, USA. Electronic address: trish.mcelroy@amgen.com.
authors.forename: Patricia L
authors.initials: PL
authors.lastname: McElroy
authors.affiliation: Oncology Research Department, Amgen Inc., Thousand Oaks, CA, USA.
authors.forename: Ping
authors.initials: P
authors.lastname: Wei
authors.affiliation: Oncology Research Department, Amgen Inc., Thousand Oaks, CA, USA.
authors.forename: Keri
authors.initials: K
authors.lastname: Buck
authors.affiliation: Oncology Research Department, Amgen Inc., Thousand Oaks, CA, USA.
authors.forename: Angus M
authors.initials: AM
authors.lastname: Sinclair
authors.affiliation: Medical Sciences Biostatistics Department, Amgen Inc., Thousand Oaks, CA, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Eschenberg
authors.affiliation: Oncology Research Department, Amgen Inc., Thousand Oaks, CA, USA.
authors.forename: Barbra
authors.initials: B
authors.lastname: Sasu
authors.affiliation: Oncology Research Department, Amgen Inc., Thousand Oaks, CA, USA.
authors.forename: Graham
authors.initials: G
authors.lastname: Molineux
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects*; D001792:Blood Platelets / Q000187:drug effects*; D004195:Disease Models, Animal; D005260:Female; D051379:Mice; D011961:Receptors, Fc; D011993:Recombinant Fusion Proteins / Q000494:pharmacology*; D013921:Thrombocytopenia / Q000097:blood / Q000139:chemically induced / Q000517:prevention & control*; D013926:Thrombopoietin / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D011961:Receptors, Fc; D011993:Recombinant Fusion Proteins; D013926:Thrombopoietin; C488777:romiplostim