{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,22]],"date-time":"2026-02-22T03:58:40Z","timestamp":1771732720957,"version":"3.50.1"},"reference-count":15,"publisher":"Oxford University Press (OUP)","issue":"12","license":[{"start":{"date-parts":[[2023,6,13]],"date-time":"2023-06-13T00:00:00Z","timestamp":1686614400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000054","name":"NCI","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","award":["P30CA016672"],"award-info":[{"award-number":["P30CA016672"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,12,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Preclinical models suggest synergy between anti-angiogenesis therapy, mammalian target of rapamycin (mTOR), and histone deacetylase inhibitors to promote anticancer activity.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>This phase I study enrolled 47 patients between April 2012 and 2018 and determined safety, maximum tolerated dose (MTD), and dose-limiting toxicities (DLTs) when combining bevacizumab, temsirolimus, and valproic acid in patients with advanced cancer.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Median age of enrolled patients was 56 years. Patients were heavily pretreated with a median of 4 lines of prior therapy. Forty-five patients (95.7%) experienced one or more treatment-related adverse events (TRAEs). Grade 3 TRAEs were lymphopenia (14.9%), thrombocytopenia (8.5%), and mucositis (6.4%). Grade 4 TRAEs included lymphopenia (2.1%) and CNS cerebrovascular ischemia (2.1%). Six patients developed DLTs across 10 dose levels with grade 3 infection, rash, mucositis, bowel perforation, elevated lipase, and grade 4 cerebrovascular ischemia. The MTD was dose level 9 (bevacizumab 5 mg\/kg days 1 and 15 intravenously (IV) plus temsirolimus 25 mg days 1, 8, 15, and 22 IV and valproic acid 5 mg\/kg on days 1-7 and 15-21 per orally (PO)). Objective response rate (ORR) was 7.9% with confirmed partial response (PRs) in 3 patients (one each in parotid gland, ovarian, and vaginal cancers). Stable disease (SD) \u2265+6 months was seen in 5 patients (13.1%). Clinical benefit state (CBR: PR + SD \u2265+6 months) was 21%.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>Combination therapy with bevacizumab, temsirolimus, and valproic acid was feasible, but there were numerous toxicities, which will require careful management for future clinical development (ClinicalTrials.gov Identifier: NCT01552434).<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/oncolo\/oyad158","type":"journal-article","created":{"date-parts":[[2023,6,13]],"date-time":"2023-06-13T18:03:39Z","timestamp":1686679419000},"page":"1100-e1292","source":"Crossref","is-referenced-by-count":9,"title":["A Phase I Trial of Bevacizumab and Temsirolimus in Combination With Valproic Acid in Advanced Solid Tumors"],"prefix":"10.1093","volume":"28","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8227-638X","authenticated-orcid":false,"given":"Blessie Elizabeth","family":"Nelson","sequence":"first","affiliation":[{"name":"Department of Investigational Cancer Therapeutics, University of Texas MD Anderson Cancer Center , Houston, TX , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Apostolia M","family":"Tsimberidou","sequence":"additional","affiliation":[{"name":"Department of Investigational Cancer Therapeutics, University of Texas MD Anderson Cancer Center , Houston, TX , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xueyao","family":"Fu","sequence":"additional","affiliation":[{"name":"Department of Investigational Cancer Therapeutics, University of Texas MD Anderson Cancer Center , Houston, TX , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Siqing","family":"Fu","sequence":"additional","affiliation":[{"name":"Department of Investigational Cancer Therapeutics, University of Texas MD Anderson Cancer Center , Houston, TX , 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