{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T00:20:05Z","timestamp":1783383605023,"version":"3.54.6"},"reference-count":40,"publisher":"Springer Science and Business Media LLC","issue":"4","license":[{"start":{"date-parts":[[2024,4,11]],"date-time":"2024-04-11T00:00:00Z","timestamp":1712793600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,4,11]],"date-time":"2024-04-11T00:00:00Z","timestamp":1712793600000},"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":["J Cancer Res Clin Oncol"],"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Purpose<\/jats:title>\n                <jats:p>The synergistic effects of combining arsenic compounds with imatinib against chronic myeloid leukemia (CML) have been established using in vitro data. We conducted a clinical trial to compare the efficacy of the arsenic realgar\u2013indigo naturalis formula (RIF) plus imatinib with that of imatinib monotherapy in patients with newly diagnosed chronic phase CML (CP-CML).<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>In this multicenter, randomized, double-blind, phase 3 trial, 191 outpatients with newly diagnosed CP-CML were randomly assigned to receive oral RIF plus imatinib (n\u2009=\u200996) or placebo plus imatinib (n\u2009=\u200995). The primary end point was the major molecular response (MMR) at 6\u00a0months. Secondary end points include molecular response 4 (MR<jats:sup>4<\/jats:sup>), molecular response 4.5 (MR<jats:sup>4.5<\/jats:sup>), progression-free survival (PFS), overall survival (OS), and adverse events.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>The median follow-up duration was 51\u00a0months. Due to the COVID-19 pandemic, the recruitment to this study had to be terminated early, on May 28, 2020. The rates of MMR had no significant statistical difference between combination and imatinib arms at 6\u00a0months and any other time during the trial. MR<jats:sup>4<\/jats:sup> rates were similar in both arms. However, the 12-month cumulative rates of MR<jats:sup>4.5<\/jats:sup> in the combination and imatinib arms were 20.8% and 10.5%, respectively (<jats:italic>p<\/jats:italic>\u2009=\u20090.043). In core treatment since the 2-year analysis, the frequency of MR<jats:sup>4.5<\/jats:sup> was 55.6% in the combination arm and 38.6% in the imatinib arm (<jats:italic>p<\/jats:italic>\u2009=\u20090.063). PFS and OS were similar at five years. The safety profiles were similar and serious adverse events were uncommon in both groups.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusion<\/jats:title>\n                <jats:p>The results of imatinib plus RIF as a first-line treatment of CP-CML compared with imatinib might be more effective for achieving a deeper molecular response (Chinadrugtrials number, CTR20170221).<\/jats:p>\n              <\/jats:sec>","DOI":"10.1007\/s00432-024-05700-x","type":"journal-article","created":{"date-parts":[[2024,4,11]],"date-time":"2024-04-11T17:01:29Z","timestamp":1712854889000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Oral arsenic plus imatinib versus imatinib solely for newly diagnosed chronic myeloid leukemia: a randomized phase 3 trial with 5-year 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