{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T13:12:11Z","timestamp":1782393131792,"version":"3.54.5"},"reference-count":49,"publisher":"Springer Science and Business Media LLC","issue":"4","license":[{"start":{"date-parts":[[2023,3,24]],"date-time":"2023-03-24T00:00:00Z","timestamp":1679616000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2023,3,24]],"date-time":"2023-03-24T00:00:00Z","timestamp":1679616000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Cancer Chemother Pharmacol"],"published-print":{"date-parts":[[2023,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Purpose<\/jats:title>\n                <jats:p>This manuscript reports on the occurrence of early and frequent erythrocytosis in advanced hepatocellular carcinoma (HCC) patients treated with lenvatinib.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>A cohort of 23 patients with advanced HCC, treated with this antiangiogenic drug for at least one month, was retrospectively analyzed.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>These patients (82.7% men, median age 58.3, cirrhosis in 60.8%) were treated between October 2019 and September 2020 with lenvatinib, as first-line systemic therapy for 82.6% of them. For 20 patients (87%), an early and significant increase in hemoglobin (Hb) level, up to 1.41\u00a0g\/dL (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001) was reported and remained elevated. Ten patients (43.5%), all men, reached erythrocytosis (Hb\u2009&gt;\u200916.5\u00a0g\/dL), 7 were treated with low-dose aspirin for primary thromboprophylaxis and 2 needed phlebotomy. None underwent thromboembolic complications. A significant Hb decrease was observed after treatment discontinuation (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05). Erythropoietin (EPO) serum levels also increased, which was attributed to HCC after immunostaining for EPO in liver biopsies. The Naranjo adverse drug reaction probability scale documented the relationship between erythrocytosis and lenvatinib and regression at treatment discontinuation. Erythrocytosis was hypothesized to be a class effect of anti-VEGF therapies, the magnitude of which might depend on the IC50 value of each molecule.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusion<\/jats:title>\n                <jats:p>This report documents the frequent occurrence of erythrocytosis during lenvatinib treatment for advanced HCC, likely secondary to EPO secretion by tumor cells through the antiangiogenic activity levatinib. An early and close monitoring of hematologic parameters is, thus, recommended, together with thromboprophylaxis by low-dose aspirin and phlebotomy in case of symptomatic erythrocytosis.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1007\/s00280-023-04519-6","type":"journal-article","created":{"date-parts":[[2023,3,24]],"date-time":"2023-03-24T09:02:57Z","timestamp":1679648577000},"page":"337-344","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Progressive erythrocytosis under lenvatinib treatment in patients with advanced hepatocellular carcinoma"],"prefix":"10.1007","volume":"91","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9567-7879","authenticated-orcid":false,"given":"Laurence","family":"Legros","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9511-3726","authenticated-orcid":false,"given":"Alina","family":"Pascale","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0791-5505","authenticated-orcid":false,"given":"Catherine","family":"Guettier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pirayeh","family":"Eftekhari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasmina Ben","family":"Merabet","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maryse","family":"Stang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6646-2481","authenticated-orcid":false,"given":"Rachel","family":"Bossevot","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2153-5384","authenticated-orcid":false,"given":"Emma","family":"Goldschmidt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8683-6818","authenticated-orcid":false,"given":"Ayhan","family":"Ulusakarya","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7747-113X","authenticated-orcid":false,"given":"Stephane","family":"Morisset","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9450-8096","authenticated-orcid":false,"given":"Ma\u00eft\u00e9","family":"Lewin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9481-3616","authenticated-orcid":false,"given":"Didier","family":"Samuel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6695-3088","authenticated-orcid":false,"given":"Olivier","family":"Rosmorduc","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2023,3,24]]},"reference":[{"key":"4519_CR1","doi-asserted-by":"publisher","first-page":"209","DOI":"10.3322\/caac.21660","volume":"71","author":"H Sung","year":"2021","unstructured":"Sung H, Ferlay J, Siegel RL et al (2021) Global Cancer Statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 71:209\u2013249. https:\/\/doi.org\/10.3322\/caac.21660","journal-title":"CA Cancer J Clin"},{"key":"4519_CR2","doi-asserted-by":"publisher","first-page":"1301","DOI":"10.1016\/S0140-6736(18)30010-2","volume":"391","author":"A Forner","year":"2018","unstructured":"Forner A, Reig M, Bruix J (2018) Hepatocellular carcinoma. Lancet 391:1301\u20131314. https:\/\/doi.org\/10.1016\/S0140-6736(18)30010-2","journal-title":"Lancet"},{"key":"4519_CR3","doi-asserted-by":"publisher","first-page":"378","DOI":"10.1056\/NEJMoa0708857","volume":"359","author":"JM Llovet","year":"2008","unstructured":"Llovet JM, Ricci S, Mazzaferro V et al (2008) Sorafenib in advanced hepatocellular carcinoma. N Engl J Med 359:378\u2013390. https:\/\/doi.org\/10.1056\/NEJMoa0708857","journal-title":"N Engl J Med"},{"key":"4519_CR4","doi-asserted-by":"publisher","first-page":"1163","DOI":"10.1016\/S0140-6736(18)30207-1","volume":"391","author":"M Kudo","year":"2018","unstructured":"Kudo M, Finn RS, Qin S et al (2018) Lenvatinib versus sorafenib in first-line treatment of patients with unresectable hepatocellular carcinoma: a randomised phase 3 non-inferiority trial. Lancet 391:1163\u20131173. https:\/\/doi.org\/10.1016\/S0140-6736(18)30207-1","journal-title":"Lancet"},{"key":"4519_CR5","doi-asserted-by":"publisher","first-page":"1894","DOI":"10.1056\/NEJMoa1915745","volume":"382","author":"RS Finn","year":"2020","unstructured":"Finn RS, Qin S, Ikeda M et al (2020) Atezolizumab plus bevacizumab in unresectable hepatocellular carcinoma. N Engl J Med 382:1894\u20131905. https:\/\/doi.org\/10.1056\/NEJMoa1915745","journal-title":"N Engl J Med"},{"key":"4519_CR6","doi-asserted-by":"publisher","first-page":"56","DOI":"10.1016\/S0140-6736(16)32453-9","volume":"389","author":"J Bruix","year":"2017","unstructured":"Bruix J, Qin S, Merle P et al (2017) Regorafenib for patients with hepatocellular carcinoma who progressed on sorafenib treatment (RESORCE): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet 389:56\u201366. https:\/\/doi.org\/10.1016\/S0140-6736(16)32453-9","journal-title":"Lancet"},{"key":"4519_CR7","doi-asserted-by":"publisher","first-page":"54","DOI":"10.1056\/NEJMoa1717002","volume":"379","author":"GK Abou-Alfa","year":"2018","unstructured":"Abou-Alfa GK, Meyer T, Cheng AL et al (2018) Cabozantinib in patients with advanced and progressing hepatocellular carcinoma. N Engl J Med 379:54\u201363. https:\/\/doi.org\/10.1056\/NEJMoa1717002","journal-title":"N Engl J Med"},{"key":"4519_CR8","doi-asserted-by":"publisher","first-page":"638747","DOI":"10.1155\/2014\/638747","volume":"2014","author":"O Tohyama","year":"2014","unstructured":"Tohyama O, Matsui J, Kodama K et al (2014) Antitumor activity of lenvatinib (e7080): an angiogenesis inhibitor that targets multiple receptor tyrosine kinases in preclinical human thyroid cancer models. J Thyroid Res 2014:638747. https:\/\/doi.org\/10.1155\/2014\/638747","journal-title":"J Thyroid Res"},{"key":"4519_CR9","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1186\/2045-824X-6-18","volume":"6","author":"Y Yamamoto","year":"2014","unstructured":"Yamamoto Y, Matsui J, Matsushima T et al (2014) Lenvatinib, an angiogenesis inhibitor targeting VEGFR\/FGFR, shows broad antitumor activity in human tumor xenograft models associated with microvessel density and pericyte coverage. Vasc Cell 6:18. https:\/\/doi.org\/10.1186\/2045-824X-6-18","journal-title":"Vasc Cell"},{"key":"4519_CR10","doi-asserted-by":"publisher","first-page":"52","DOI":"10.1055\/s-0030-1247132","volume":"30","author":"R Lencioni","year":"2010","unstructured":"Lencioni R, Llovet JM (2010) Modified RECIST (mRECIST) assessment for hepatocellular carcinoma. Semin Liver Dis 30:52\u201360. https:\/\/doi.org\/10.1055\/s-0030-1247132","journal-title":"Semin Liver Dis"},{"key":"4519_CR11","doi-asserted-by":"publisher","first-page":"2391","DOI":"10.1182\/blood-2016-03-643544","volume":"127","author":"DA Arber","year":"2016","unstructured":"Arber DA, Orazi A, Hasserjian R et al (2016) The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. Blood 127:2391\u20132405. https:\/\/doi.org\/10.1182\/blood-2016-03-643544","journal-title":"Blood"},{"key":"4519_CR12","doi-asserted-by":"publisher","first-page":"239","DOI":"10.1038\/clpt.1981.154","volume":"30","author":"CA Naranjo","year":"1981","unstructured":"Naranjo CA, Busto U, Sellers EM et al (1981) A method for estimating the probability of adverse drug reactions. Clin Pharmacol Ther 30:239\u2013245. https:\/\/doi.org\/10.1038\/clpt.1981.154","journal-title":"Clin Pharmacol Ther"},{"key":"4519_CR13","doi-asserted-by":"publisher","first-page":"127","DOI":"10.1111\/j.1472-8206.2007.00552.x","volume":"22","author":"A Bate","year":"2008","unstructured":"Bate A, Lindquist M, Edwards IR (2008) The application of knowledge discovery in databases to post-marketing drug safety: example of the WHO database. Fundam Clin Pharmacol 22:127\u2013140. https:\/\/doi.org\/10.1111\/j.1472-8206.2007.00552.x","journal-title":"Fundam Clin Pharmacol"},{"key":"4519_CR14","doi-asserted-by":"publisher","first-page":"472","DOI":"10.1200\/JCO.2008.20.1087","volume":"27","author":"I Alexandre","year":"2009","unstructured":"Alexandre I, Billemont B, Meric JB et al (2009) Axitinib induces paradoxical erythropoietin synthesis in metastatic renal cell carcinoma. J Clin Oncol 27:472\u2013473. https:\/\/doi.org\/10.1200\/JCO.2008.20.1087","journal-title":"J Clin Oncol"},{"key":"4519_CR15","doi-asserted-by":"publisher","first-page":"26","DOI":"10.4103\/JCO.JCO_24_18","volume":"2","author":"PM Langbroek","year":"2019","unstructured":"Langbroek PM, Pol\u00e9e MB, de Graaf H (2019) Escalating erythrocytosis after start of pazopanib-treatment in metastatic renal cell carcinoma. J Curr Oncol 2:26\u201328","journal-title":"J Curr Oncol"},{"key":"4519_CR16","doi-asserted-by":"publisher","first-page":"766","DOI":"10.1177\/1078155220950440","volume":"27","author":"M Fanelli","year":"2021","unstructured":"Fanelli M, Caputo F, Cerma K et al (2021) Pazopanib-related secondary polycythemia in metastatic myxofibrosarcoma: a case report and review of the literature. J Oncol Pharm Pract 27:766\u2013770. https:\/\/doi.org\/10.1177\/1078155220950440","journal-title":"J Oncol Pharm Pract"},{"key":"4519_CR17","doi-asserted-by":"publisher","first-page":"e391","DOI":"10.1016\/j.clgc.2015.07.003","volume":"13","author":"W Wang","year":"2015","unstructured":"Wang W, Cheng J, Mallon C et al (2015) Symptomatic secondary polycythemia induced by anti-VEGF therapy for the treatment of metastatic renal cell carcinoma: a case series and review. Clin Genitourin Cancer 13:e391-395. https:\/\/doi.org\/10.1016\/j.clgc.2015.07.003","journal-title":"Clin Genitourin Cancer"},{"key":"4519_CR18","doi-asserted-by":"publisher","first-page":"E449","DOI":"10.5489\/cuaj.4519","volume":"11","author":"N Bukhari","year":"2017","unstructured":"Bukhari N, Winquist E (2017) Case: Secondary polycythemia due to pazopanib in patients with metastatic renal cell carcinoma. Can Urol Assoc J 11:E449\u2013E450. https:\/\/doi.org\/10.5489\/cuaj.4519","journal-title":"Can Urol Assoc J"},{"key":"4519_CR19","first-page":"6980","volume":"9","author":"H Hamad","year":"2016","unstructured":"Hamad H, Adab K, Shah M (2016) Sunitinib-induced erythrocytosis: case report and review of literature. Int J Clin Exp Med 9:6980\u20136982","journal-title":"Int J Clin Exp Med"},{"key":"4519_CR20","doi-asserted-by":"publisher","first-page":"4047","DOI":"10.1200\/JCO.2008.18.3525","volume":"26","author":"DT Alexandrescu","year":"2008","unstructured":"Alexandrescu DT, McClure R, Farzanmehr H et al (2008) Secondary erythrocytosis produced by the tyrosine kinase inhibitors sunitinib and sorafenib. J Clin Oncol 26:4047\u20134048. https:\/\/doi.org\/10.1200\/JCO.2008.18.3525","journal-title":"J Clin Oncol"},{"key":"4519_CR21","doi-asserted-by":"publisher","first-page":"2008","DOI":"10.1200\/jco.2008.26.15_suppl.16096","volume":"26","author":"LCKC Harshman","year":"2008","unstructured":"Harshman LCKC, Srinivas S (2008) Bevacizumab-associated erythrocytosis in metastatic renal cell carcinoma. J Clin Oncol 26:2008","journal-title":"J Clin Oncol"},{"key":"4519_CR22","doi-asserted-by":"publisher","first-page":"475","DOI":"10.1177\/10781552211039108","volume":"28","author":"J Kaur","year":"2022","unstructured":"Kaur J, Tuler S, Dasanu CA (2022) Sustained erythrocytosis due to the use of Lenvatinib. J Oncol Pharm Pract 28:475\u2013478. https:\/\/doi.org\/10.1177\/10781552211039108","journal-title":"J Oncol Pharm Pract"},{"key":"4519_CR23","doi-asserted-by":"publisher","first-page":"221","DOI":"10.1016\/j.jceh.2019.01.004","volume":"9","author":"A Jindal","year":"2019","unstructured":"Jindal A, Thadi A, Shailubhai K (2019) Hepatocellular carcinoma: etiology and current and future drugs. J Clin Exp Hepatol 9:221\u2013232. https:\/\/doi.org\/10.1016\/j.jceh.2019.01.004","journal-title":"J Clin Exp Hepatol"},{"key":"4519_CR24","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1053\/j.seminoncol.2018.11.004","volume":"46","author":"ME Cabanillas","year":"2019","unstructured":"Cabanillas ME, Takahashi S (2019) Managing the adverse events associated with lenvatinib therapy in radioiodine-refractory differentiated thyroid cancer. Semin Oncol 46:57\u201364. https:\/\/doi.org\/10.1053\/j.seminoncol.2018.11.004","journal-title":"Semin Oncol"},{"key":"4519_CR25","doi-asserted-by":"publisher","first-page":"1135","DOI":"10.1089\/thy.2016.0549","volume":"27","author":"N Kiyota","year":"2017","unstructured":"Kiyota N, Robinson B, Shah M et al (2017) Defining radioiodine-refractory differentiated thyroid cancer: efficacy and safety of lenvatinib by radioiodine-refractory criteria in the SELECT trial. Thyroid 27:1135\u20131141. https:\/\/doi.org\/10.1089\/thy.2016.0549","journal-title":"Thyroid"},{"key":"4519_CR26","doi-asserted-by":"publisher","first-page":"621","DOI":"10.1056\/NEJMoa1406470","volume":"372","author":"M Schlumberger","year":"2015","unstructured":"Schlumberger M, Tahara M, Wirth LJ et al (2015) Lenvatinib versus placebo in radioiodine-refractory thyroid cancer. N Engl J Med 372:621\u2013630. https:\/\/doi.org\/10.1056\/NEJMoa1406470","journal-title":"N Engl J Med"},{"key":"4519_CR27","first-page":"464","volume":"163","author":"O Schober","year":"1987","unstructured":"Schober O, G\u00fcnter HH, Schwarzrock R et al (1987) Long-term hematologic changes caused by radioiodine treatment of thyroid cancer. I. Peripheral blood changes. Strahlenther Onkol 163:464\u2013474","journal-title":"Strahlenther Onkol"},{"key":"4519_CR28","doi-asserted-by":"publisher","first-page":"1193","DOI":"10.1507\/endocrj.EJ20-0242","volume":"67","author":"W Yi","year":"2020","unstructured":"Yi W, Kim BH, Kim M et al (2020) Short-term bone marrow suppression in differentiated thyroid cancer patients after radioactive iodine treatment. Endocr J 67:1193\u20131198. https:\/\/doi.org\/10.1507\/endocrj.EJ20-0242","journal-title":"Endocr J"},{"key":"4519_CR29","doi-asserted-by":"publisher","first-page":"683","DOI":"10.1089\/thy.2018.0423","volume":"29","author":"H Duskin-Bitan","year":"2019","unstructured":"Duskin-Bitan H, Leibner A, Amitai O et al (2019) Bone-marrow suppression in elderly patients following empiric radioiodine therapy: real-life data. Thyroid 29:683\u2013691. https:\/\/doi.org\/10.1089\/thy.2018.0423","journal-title":"Thyroid"},{"key":"4519_CR30","doi-asserted-by":"publisher","first-page":"524","DOI":"10.1182\/blood.V71.2.524.524","volume":"71","author":"ST Koury","year":"1988","unstructured":"Koury ST, Bondurant MC, Koury MJ (1988) Localization of erythropoietin synthesizing cells in murine kidneys by in situ hybridization. Blood 71:524\u2013527","journal-title":"Blood"},{"key":"4519_CR31","doi-asserted-by":"publisher","first-page":"427","DOI":"10.1182\/blood.V13.5.427.427","volume":"13","author":"AJ McFadzean","year":"1958","unstructured":"McFadzean AJ, Todd D, Tsang KC (1958) Polycythemia in primary carcinoma of the liver. Blood 13:427\u2013435","journal-title":"Blood"},{"key":"4519_CR32","doi-asserted-by":"publisher","first-page":"2485","DOI":"10.1002\/1097-0142(19861201)58:11<2485::aid-cncr2820581122>3.0.co;2-n","volume":"58","author":"MC Kew","year":"1986","unstructured":"Kew MC, Fisher JW (1986) Serum erythropoietin concentrations in patients with hepatocellular carcinoma. Cancer 58:2485\u20132488. https:\/\/doi.org\/10.1002\/1097-0142(19861201)58:11%3c2485::aid-cncr2820581122%3e3.0.co;2-n","journal-title":"Cancer"},{"key":"4519_CR33","doi-asserted-by":"publisher","first-page":"1357","DOI":"10.1002\/hep.1840180612","volume":"18","author":"S Sakisaka","year":"1993","unstructured":"Sakisaka S, Watanabe M, Tateishi H et al (1993) Erythropoietin production in hepatocellular carcinoma cells associated with polycythemia: immunohistochemical evidence. Hepatology 18:1357\u20131362","journal-title":"Hepatology"},{"key":"4519_CR34","doi-asserted-by":"publisher","first-page":"2731","DOI":"10.1128\/mcb.6.7.2731-2733.1986","volume":"6","author":"MC Bondurant","year":"1986","unstructured":"Bondurant MC, Koury MJ (1986) Anemia induces accumulation of erythropoietin mRNA in the kidney and liver. Mol Cell Biol 6:2731\u20132733. https:\/\/doi.org\/10.1128\/mcb.6.7.2731-2733.1986","journal-title":"Mol Cell Biol"},{"key":"4519_CR35","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1182\/blood.V39.1.31.31","volume":"39","author":"JC Schooley","year":"1972","unstructured":"Schooley JC, Mahlmann LJ (1972) Erythropoietin production in the anephric rat. I. Relationship between nephrectomy, time of hypoxic exposure, and erythropoietin production. Blood 39:31\u201338","journal-title":"Blood"},{"key":"4519_CR36","doi-asserted-by":"publisher","first-page":"2497","DOI":"10.1182\/blood.V77.11.2497.2497","volume":"77","author":"ST Koury","year":"1991","unstructured":"Koury ST, Bondurant MC, Koury MJ et al (1991) Localization of cells producing erythropoietin in murine liver by in situ hybridization. Blood 77:2497\u20132503","journal-title":"Blood"},{"key":"4519_CR37","first-page":"825","volume":"12","author":"P Paul","year":"1984","unstructured":"Paul P, Rothmann SA, McMahon JT et al (1984) Erythropoietin secretion by isolated rat Kupffer cells. Exp Hematol 12:825\u2013830","journal-title":"Exp Hematol"},{"key":"4519_CR38","doi-asserted-by":"publisher","first-page":"793","DOI":"10.1038\/nm1428","volume":"12","author":"BY Tam","year":"2006","unstructured":"Tam BY, Wei K, Rudge JS et al (2006) VEGF modulates erythropoiesis through regulation of adult hepatic erythropoietin synthesis. Nat Med 12:793\u2013800. https:\/\/doi.org\/10.1038\/nm1428","journal-title":"Nat Med"},{"key":"4519_CR39","doi-asserted-by":"publisher","first-page":"1255","DOI":"10.1016\/S0140-6736(03)14567-9","volume":"362","author":"M Henke","year":"2003","unstructured":"Henke M, Laszig R, R\u00fcbe C et al (2003) Erythropoietin to treat head and neck cancer patients with anaemia undergoing radiotherapy: randomised, double-blind, placebo-controlled trial. Lancet 362:1255\u20131260. https:\/\/doi.org\/10.1016\/S0140-6736(03)14567-9","journal-title":"Lancet"},{"key":"4519_CR40","doi-asserted-by":"publisher","first-page":"1197","DOI":"10.1200\/JCO.2015.63.5649","volume":"34","author":"B Leyland-Jones","year":"2016","unstructured":"Leyland-Jones B, Bondarenko I, Nemsadze G et al (2016) A randomized, open-label, multicenter, phase iii study of epoetin alfa versus best standard of care in anemic patients with metastatic breast cancer receiving standard chemotherapy. J Clin Oncol 34:1197\u20131207. https:\/\/doi.org\/10.1200\/JCO.2015.63.5649","journal-title":"J Clin Oncol"},{"key":"4519_CR41","doi-asserted-by":"publisher","first-page":"119","DOI":"10.1186\/s12935-017-04","volume":"17","author":"S Miao","year":"2017","unstructured":"Miao S, Wang SM, Cheng X et al (2017) Erythropoietin promoted the proliferation of hepatocellular carcinoma through hypoxia induced translocation of its specific receptor. Cancer Cell Int 17:119. https:\/\/doi.org\/10.1186\/s12935-017-04","journal-title":"Cancer Cell Int"},{"key":"4519_CR42","first-page":"4033","volume":"8","author":"Y Zhihong","year":"2015","unstructured":"Zhihong Y, Baocun S, Xiulan Z et al (2015) Erythropoietin and erythropoietin receptor in hepatocellular carcinoma: correlation with vasculogenic mimicry and poor prognosis. Int J Clin Exp Pathol 8:4033\u20134043","journal-title":"Int J Clin Exp Pathol"},{"key":"4519_CR43","doi-asserted-by":"publisher","first-page":"150","DOI":"10.1177\/030089160208800214","volume":"88","author":"G Westphal","year":"2002","unstructured":"Westphal G, Niederberger E, Blum C et al (2002) Erythropoietin and G-CSF receptors in human tumor cells: expression and aspects regarding functionality. Tumori 88:150\u2013159. https:\/\/doi.org\/10.1177\/030089160208800214","journal-title":"Tumori"},{"issue":"Suppl 5","key":"4519_CR44","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1634\/theoncologist.9-90005-18","volume":"9","author":"F Farrell","year":"2004","unstructured":"Farrell F, Lee A (2004) The erythropoietin receptor and its expression in tumor cells and other tissues. Oncologist 9(Suppl 5):18\u201330. https:\/\/doi.org\/10.1634\/theoncologist.9-90005-18","journal-title":"Oncologist"},{"key":"4519_CR45","doi-asserted-by":"publisher","first-page":"965","DOI":"10.1111\/hpb.12076","volume":"15","author":"M Shin","year":"2013","unstructured":"Shin M, Hong D, Zhang Z et al (2013) Expression and functional significance of the erythropoietin receptor in hepatocellular carcinoma. HPB (Oxford) 15:965\u2013975. https:\/\/doi.org\/10.1111\/hpb.12076","journal-title":"HPB (Oxford)"},{"key":"4519_CR46","doi-asserted-by":"publisher","first-page":"347","DOI":"10.1017\/CBO9780511544897.048","volume-title":"Uncommon causes of stroke","author":"J Dashe","year":"2008","unstructured":"Dashe J (2008) Hyperviscosity and stroke. In: Caplan L, Bogousslavsky J (eds) Uncommon causes of stroke. Cambridge University Press, Cambridge, pp 347\u2013356"},{"key":"4519_CR47","doi-asserted-by":"publisher","first-page":"653","DOI":"10.3324\/haematol.2018.210732","volume":"104","author":"VR Gordeuk","year":"2019","unstructured":"Gordeuk VR, Key NS, Prchal JT (2019) Re-evaluation of hematocrit as a determinant of thrombotic risk in erythrocytosis. Haematologica 104:653\u2013658. https:\/\/doi.org\/10.3324\/haematol.2018.210732","journal-title":"Haematologica"},{"key":"4519_CR48","doi-asserted-by":"publisher","first-page":"31","DOI":"10.3109\/07853899309147854","volume":"25","author":"T Somer","year":"1993","unstructured":"Somer T, Meiselman HJ (1993) Disorders of blood viscosity. Ann Med 25:31\u201339. https:\/\/doi.org\/10.3109\/07853899309147854","journal-title":"Ann Med"},{"key":"4519_CR49","doi-asserted-by":"publisher","first-page":"1203","DOI":"10.1093\/neuonc\/nor223","volume":"14","author":"TS Armstrong","year":"2012","unstructured":"Armstrong TS, Wen PY, Gilbert MR et al (2012) Management of treatment-associated toxicites of anti-angiogenic therapy in patients with brain tumors. Neuro Oncol 14:1203\u20131214. https:\/\/doi.org\/10.1093\/neuonc\/nor223","journal-title":"Neuro Oncol"}],"container-title":["Cancer Chemotherapy and Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00280-023-04519-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00280-023-04519-6\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00280-023-04519-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,4,3]],"date-time":"2023-04-03T06:15:13Z","timestamp":1680502513000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00280-023-04519-6"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,3,24]]},"references-count":49,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2023,4]]}},"alternative-id":["4519"],"URL":"https:\/\/doi.org\/10.1007\/s00280-023-04519-6","relation":{},"ISSN":["0344-5704","1432-0843"],"issn-type":[{"value":"0344-5704","type":"print"},{"value":"1432-0843","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,3,24]]},"assertion":[{"value":"2 December 2022","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"3 March 2023","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"24 March 2023","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"LL reports personal fees from Bristol Myers-Squibb (BMS), Incyte, Novartis, and Pfizer and research support from Incyte outside of the submitted work. OR reports participation on data safety monitoring boards or advisory boards for Bayer, Eisai, and Sitrex.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}]}}