{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,6]],"date-time":"2026-03-06T04:15:56Z","timestamp":1772770556947,"version":"3.50.1"},"reference-count":25,"publisher":"Springer Science and Business Media LLC","issue":"5","license":[{"start":{"date-parts":[[2024,8,3]],"date-time":"2024-08-03T00:00:00Z","timestamp":1722643200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,8,3]],"date-time":"2024-08-03T00:00:00Z","timestamp":1722643200000},"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":["Invest New Drugs"],"published-print":{"date-parts":[[2024,10]]},"abstract":"<jats:sec>\n                <jats:title>Summary<\/jats:title>\n                <jats:p>Plocabulin (Plo) induces depolymerization of tubulin fibers with disorganization and fragmentation of the microtubule network leading to mitosis. Plo combined with gemcitabine (Gem) showed synergistic anti-tumor activity in preclinical studies.\u00a0This phase I trial evaluated the safety, pharmacokinetics (PK) and efficacy of Plo 10-min infusion plus Gem on Day 1 and 8 every 3-week in patients with advanced solid tumors.\u00a0Fifty-seven patients were enrolled into 8 dose levels (DLs); 74%: females; 74%: ECOG performance status 1; median age: 62\u00a0years; median number of prior lines of therapy:3. Dose-limiting toxicities (DLT) in Cycle 1 were grade (G) 3 intestinal obstruction at the maximum tolerated dose (MTD), G3 peripheral sensory neuropathy (PSN), G3 abdominal pain, and G4 thrombocytopenia (1 patient each). The highest DL (DL8: Plo 10.5\u00a0mg\/m<jats:sup>2<\/jats:sup>\/Gem 1000\u00a0mg\/m<jats:sup>2<\/jats:sup>) was the MTD. Accrual into DL7 (Plo 10.0\u00a0mg\/m<jats:sup>2<\/jats:sup>\/Gem 1000\u00a0mg\/m<jats:sup>2<\/jats:sup>) was stopped before it was formally defined as the recommended dose (RD). Most common treatment-related adverse events (AEs) were fatigue (56%), nausea (55%), diarrhea (31%); G3\/4 hematologic toxicities comprised anemia (35%), neutropenia (27%) and thrombocytopenia (17%). No treatment-related deaths occurred. PK parameters for Gem or dFdU at all DLs were in line with reference values from the literature. Six of 46 evaluable pts were responders (overall response rate:13%). Of note, 2 partial responses (PR) and 2 stable disease (SD)\u2009\u2265\u20094\u00a0months occurred among 13 pts with ovarian cancer.\u00a0The combination of Plo and Gem is well tolerated. The MTD was Plo 10.5\u00a0mg\/m<jats:sup>2<\/jats:sup>\/Gem 1000\u00a0mg\/m<jats:sup>2<\/jats:sup>. No PK drug-drug interaction was found. The most encouraging outcome occurred in ovarian cancer patients.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1007\/s10637-024-01458-8","type":"journal-article","created":{"date-parts":[[2024,8,3]],"date-time":"2024-08-03T07:02:07Z","timestamp":1722668527000},"page":"481-491","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["A phase I safety and efficacy clinical trial of plocabulin and gemcitabine in patients with advanced solid tumors"],"prefix":"10.1007","volume":"42","author":[{"given":"Mohammad H.","family":"Ghalib","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mariano Provencio","family":"Pulla","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria J.","family":"De Miguel Luken","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Virginia Calvo","family":"de Juan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Imran","family":"Chaudhary","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M Bakri","family":"Hammami","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sindhu","family":"Vikash","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Radhashree","family":"Maitra","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sara","family":"Martinez","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carmen","family":"Kahatt","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sonia","family":"Extremera","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Salvador","family":"Fudio","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2798-7568","authenticated-orcid":false,"given":"Sanjay","family":"Goel","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2024,8,3]]},"reference":[{"key":"1458_CR1","doi-asserted-by":"publisher","unstructured":"Mart\u00edn MJ, Coello L, Fern\u00e1ndez R, Reyes F, Rodr\u00edguez A, Murcia C et al (2013) Isolation and first total synthesis of PM050489 and PM060184, two new marine anticancer compounds. 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The study was approved by the ethics committee of each participating institution.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"SM, CK, SE and SF report personal fees for salary as full-time employee and stock ownership from Pharma Mar, outside the submitted work.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Disclosure of potential conflicts of interest"}},{"value":"Presented in part at the Annual Meetings of the European Society of Medical Oncology (ESMO) in 2023, Madrid, Spain.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Presentations"}}]}}