{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,3]],"date-time":"2026-02-03T21:40:31Z","timestamp":1770154831515,"version":"3.49.0"},"reference-count":11,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2011,7,1]],"date-time":"2011-07-01T00:00:00Z","timestamp":1309478400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2011,7,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Elsamitrucin, the most potent topoisomerase II inhibitor available, is unique in that it does not cause neutropenia or cardiotoxicosis. It has antitumor activity in human patients with relapsed or refractory non-Hodgkin's lymphoma.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>To determine the maximum tolerated dose (MTD), safety, and toxicity of elsamitrucin when administered to tumor-bearing dogs and to evaluate the incidence and severity of adverse events.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Animals<\/jats:title>\n                    <jats:p>Twenty client-owned dogs with spontaneous malignant solid tumors or lymphoma that were refractory to, or for which the owner declined, conventional therapy were enrolled.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Prospective, open-label, single-agent study. Escalating doses of elsamitrucin were administered once weekly IV for up to 16 weeks in a modified 3 + 3 Phase I design. The starting dose was 0.06\u2003mg\/kg with escalation to 0.08 and 0.09\u2003mg\/kg. Dogs that remained on the study were monitored for evidence of toxicoses for at least 4 weeks and for survival every 2 months.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Serious adverse events (SAEs) possibly attributable to elsamitrucin include: 1 dog developed heart failure and another developed hepatotoxicosis manifested by increased alanine aminotransferase, alkaline phosphatase, and total bilirubin (0.06\u2003mg\/kg dose); 1 dog developed severe anorexia and diarrhea, another developed severe diarrhea alone, and a 3rd dog went into cardiac arrest (0.09\u2003mg\/kg dose). A dose of 0.08\u2003mg\/kg was well tolerated with no SAEs.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions and Clinical Importance<\/jats:title>\n                    <jats:p>The MTD and recommended dose for Phase II trials of elsamitrucin is 0.08\u2003mg\/kg IV weekly. Elsamitrucin might be considered for combination protocols with myelosuppressive chemotherapy agents.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/j.1939-1676.2011.0752.x","type":"journal-article","created":{"date-parts":[[2011,7,7]],"date-time":"2011-07-07T15:59:04Z","timestamp":1310054344000},"page":"897-902","source":"Crossref","is-referenced-by-count":4,"title":["An Open-Label, Dose-Escalating Phase I Study of Elsamitrucin (SPI 28090) in Treatment of Malignant Solid Tumors in Dogs"],"prefix":"10.1093","volume":"25","author":[{"given":"S.C.","family":"Fiocchi","sequence":"first","affiliation":[{"name":"Veterinary Cancer Group , Tustin, CA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"K.A.","family":"Selting","sequence":"additional","affiliation":[{"name":"University of Missouri Department of Veterinary Medicine and Surgery, , Columbia, MO"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M.P.","family":"Rosenberg","sequence":"additional","affiliation":[{"name":"Veterinary Cancer Group , Tustin, CA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"P.","family":"Kolli","sequence":"additional","affiliation":[{"name":"Spectrum Pharmaceuticals , Irvine, CA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"G.","family":"Lenaz","sequence":"additional","affiliation":[{"name":"Spectrum Pharmaceuticals , Irvine, CA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"C.","family":"Henry","sequence":"additional","affiliation":[{"name":"University of Missouri Department of Veterinary Medicine and Surgery, , Columbia, MO"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2011,7,1]]},"reference":[{"key":"2026020303471076900_b1","doi-asserted-by":"crossref","first-page":"784","DOI":"10.7164\/antibiotics.39.784","article-title":"Elsamicins, new antitumor antibiotics related to chartreusin. 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