Systematic literature review and meta-analysis on use of thrombopoietic agents for chemotherapy-induced thrombocytopenia Review


Authors: Soff, G. A.; Ray-Coquard, I.; Rivera, L. J. M.; Fryzek, J.; Mullins, M.; Bylsma, L. C.; Park, J. K.
Review Title: Systematic literature review and meta-analysis on use of thrombopoietic agents for chemotherapy-induced thrombocytopenia
Abstract: Background Currently, there are no approved options to prevent or treat chemotherapy-induced thrombocytopenia (CIT). We performed a systematic literature review and meta-analysis on use of thrombopoietic agents for CIT. Patients and methods We searched Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, PubMed, EMBASE, ClinicalTrials.gov , and health technology assessments from January 1995 to March 2021 for studies evaluating thrombopoietic agents for CIT, including recombinant human thrombopoietin (rhTPO), megakaryocyte growth and development factor (MGDF), romiplostim, and eltrombopag. Random effects meta-analyses were conducted for efficacy and safety endpoints. Results We screened 1503 titles/abstracts, assessed 138 articles, and abstracted data from 39 publications (14 recombinant human thrombopoietin, 7 megakaryocyte growth and development factor, 9 romiplostim, 8 eltrombopag, and 1 romiplostim/eltrombopag). Random effects meta-analyses of data from multiple studies comparing thrombopoietic agents versus control (comparator, placebo, or no treatment) showed that thrombopoietic agents did not significantly improve chemotherapy dose delays and/or reductions (21.1% vs 40.4%, P= 0.364), grade 3/4 thrombocytopenia (39.3% vs 34.8%; P= 0.789), platelet transfusions (16.7% vs 31.7%, P = 0.111), grade >= 2 bleeding (6.7% vs 16.5%; P= 0.250), or thrombosis (7.6% vs 12.5%; P = 0.131). However, among individual studies comparing thrombopoietic agents with placebo or no treatment, thrombopoietic agents positively improved outcomes in some studies, including significantly increasing mean peak platelet counts (186 x 10(9)/L with rhTPO vs 122 x 10(9)/L with no treatment; P < 0.05) in one study and significantly increasing platelet count at nadir (56 x 10(9)/L with rhTPO vs 28 x 10(9)/L with not treatment; P < 0.05) in another study. Safety findings included thrombosis (n = 23 studies) and bleeding (n = 11), with no evidence of increased thrombosis risk with thrombopoietic agents. Conclusion Our analyses generate the hypothesis that thrombopoietic agents may benefit patients with CIT. Further studies with well-characterized bleeding and platelet thresholds are warranted to explore the possible benefits of thrombopoietic agents for CIT.
Keywords: placebo-controlled trial; double-blind; chronic; phase-i trial; cancer-patients; acute myeloid-leukemia; advanced solid tumors; human megakaryocyte growth; recombinant human thrombopoietin; immune thrombocytopenia; gemcitabine-based chemotherapy
Journal Title: PLoS ONE
Volume: 17
Issue: 6
ISSN: 1932-6203
Publisher: Public Library of Science  
Date Published: 2022-06-09
Start Page: e0257673
Language: English
ACCESSION: WOS:000843619700004
DOI: 10.1371/journal.pone.0257673
PROVIDER: wos
PMCID: PMC9183450
PUBMED: 35679540
Notes: Review -- e0257673 -- Source: Wos
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  1. Gerald A Soff
    93 Soff