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Compared with other cytotoxic chemotherapies, these drugs generally have a favorable safety profile, but hematologic and gastrointestinal toxicities remain common. DFP-11207 is a novel oral cytotoxic agent that combines a 5-FU pro-drug with a reversible DPD inhibitor and a potent inhibitor of OPRT, resulting in enhanced pharmacological activity of 5-FU with decreased gastrointestinal and myelosuppressive toxicities. In this Phase I study (NCT02171221), DFP-11207 was administered orally daily, in doses escalating from 40\u00a0mg\/m<jats:sup>2<\/jats:sup>\/day to 400\u00a0mg\/m<jats:sup>2<\/jats:sup>\/day in patients with esophageal, colorectal, gastric, pancreatic or gallbladder cancer (<jats:italic>n<\/jats:italic>\u00a0=\u200923). It was determined that DFP-11207 at the dose of 330\u00a0mg\/m<jats:sup>2<\/jats:sup>\/day administered every 12\u00a0hours was well-tolerated with mild myelosuppressive and gastrointestinal toxicities. The pharmacokinetic analysis determined that the 5-FU levels were in the therapeutic range at this dose. In addition, fasted or fed states had no influence on the 5-FU levels (patients serving as their own controls). Among 21 efficacy evaluable patients, 7 patients had stable disease (33.3%), of which two had prolonged stable disease of &gt;6\u00a0months duration. DFP-11207 can be explored as monotherapy or easily substitute 5-FU, capecitabine, or S-1 in combination regimens.<\/jats:p>","DOI":"10.1007\/s10637-020-00939-w","type":"journal-article","created":{"date-parts":[[2020,5,6]],"date-time":"2020-05-06T11:02:47Z","timestamp":1588762967000},"page":"1763-1773","update-policy":"http:\/\/dx.doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Phase I study of DFP-11207, a novel oral fluoropyrimidine with reasonable AUC and low Cmax and improved tolerability, in patients with solid tumors"],"prefix":"10.1007","volume":"38","author":[{"given":"Jaffer A.","family":"Ajani","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Milind","family":"Javle","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cathy","family":"Eng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David","family":"Fogelman","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jackie","family":"Smith","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Barry","family":"Anderson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chun","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kenzo","family":"Iizuka","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2020,5,6]]},"reference":[{"issue":"4561","key":"939_CR1","doi-asserted-by":"publisher","first-page":"663","DOI":"10.1038\/179663a0","volume":"179","author":"C Heidelberger","year":"1957","unstructured":"Heidelberger C, Chaudhuri NK, Danneberg P et al (1957) Fluorinated Pyrimidines, a new class of tumour-inhibitory compounds. 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Milind Javle declares receiving honoraria or consultation fees from Rafael Pharmaceuticals, Incyte, Pieris Pharmaceuticals, Merck, Novartis, Seattle Genetics, BeiGene, QED Therapeutics, Bayer. Cathy Eng declares that she has no conflict of interest. David Fogelman declares receiving grants \/ research support from Delta-Fly Pharma, Inc. Jackie Smith declares that she has no conflict of interest. Barry Anderson declares that he has no conflict of interest. Chun Zhang is an employee of Delta-Fly Pharma, Inc. Kenzo Iizuka is an executive officer of Delta-Fly Pharma, Inc.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"This study was conducted in accordance with International Conference on Harmonization Good Clinical Practice (ICH\/GCP), the protocol, all applicable regulatory requirements, and guiding principles of the Declaration of Helsinki and its later amendments.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}},{"value":"Informed consent was obtained from all individual participants included in the study.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Informed consent"}}]}}