{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T05:07:51Z","timestamp":1785388071253,"version":"3.55.0"},"reference-count":42,"publisher":"Public Library of Science (PLoS)","issue":"12","license":[{"start":{"date-parts":[[2022,12,22]],"date-time":"2022-12-22T00:00:00Z","timestamp":1671667200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NovaVive"},{"name":"NovaVive"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>Canine splenic hemangiosarcoma (HSA) is an aggressive tumor with a short overall survival time (OST) despite treatment with splenectomy and adjuvant doxorubicin. Modulation of the immune system has been shown to be effective for a variety of human tumors, and may be effective for canine tumors, including HSA. Immunocidin\u00ae is a non-specific immunotherapy based on a mycobacterial cell wall fraction. Preliminary work suggests Immunocidin\u00ae is safe to give intravenously (IV) in tumor-bearing dogs. This work aimed to evaluate the safety of doxorubicin and Immunocidin\u00ae combination in dogs with naturally occurring splenic HSA. A secondary aim of this study was to collect preliminary efficacy data to support a subsequent comprehensive, prospective clinical trial in canine patients with HSA, if the combination of doxorubicin and Immunocidin\u00ae was found to be safe. Eighteen dogs with stage II-III splenic HSA were recruited to receive 5 doses of sequential IV doxorubicin and Immunocidin\u00ae at two-week intervals following splenectomy. Adverse events (AEs) were graded according to the Veterinary Cooperative Oncology Group v1.1 (VCOG) scheme. Overall survival time was calculated from the date of splenectomy to date of death or loss to follow-up. AEs during administration were infrequent, the most common being hypertension. One patient developed limb and facial twitching and was removed from the study. After infusion, common AEs included lethargy, hyporexia, and diarrhea. One patient developed VCOG grade 5 diarrhea, thrombocytopenia, and anemia. Modifications in the treatment regimen were made to prevent these signs in subsequent patients. The median OST in dogs treated with the combination therapy was estimated at 147 days (range: 39\u2013668 days). Although generally safe, the combination of doxorubicin and Immunocidin\u00ae appeared to cause more gastrointestinal effects than doxorubicin alone, and no apparent improvement in OST was noted in this population of dogs.<\/jats:p>","DOI":"10.1371\/journal.pone.0279594","type":"journal-article","created":{"date-parts":[[2022,12,22]],"date-time":"2022-12-22T18:47:42Z","timestamp":1671734862000},"page":"e0279594","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":9,"title":["Pilot safety evaluation of doxorubicin chemotherapy combined with non-specific immunotherapy (Immunocidin\u00ae) for canine splenic hemangiosarcoma"],"prefix":"10.1371","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4350-0614","authenticated-orcid":true,"given":"Margaret L.","family":"Musser","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanna 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