Phase I trial of 6-hour infusion of glufosfamide, a new alkylating agent with potentially enhanced selectivity for tumors that overexpress transmembrane glucose transporters: a study of the European Organization for Research and Treatment of Cancer Early Clinical Studies Group

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dc.contributor.authorBriasoulis, E.en
dc.contributor.authorJudson, I.en
dc.contributor.authorPavlidis, N.en
dc.contributor.authorBeale, P.en
dc.contributor.authorWanders, J.en
dc.contributor.authorGroot, Y.en
dc.contributor.authorVeerman, G.en
dc.contributor.authorSchuessler, M.en
dc.contributor.authorNiebch, G.en
dc.contributor.authorSiamopoulos, K.en
dc.contributor.authorTzamakou, E.en
dc.contributor.authorRammou, D.en
dc.contributor.authorWolf, L.en
dc.contributor.authorWalker, R.en
dc.contributor.authorHanauske, A.en
dc.date.accessioned2015-11-24T18:58:57Z
dc.date.available2015-11-24T18:58:57Z
dc.identifier.issn0732-183X-
dc.identifier.urihttps://olympias.lib.uoi.gr/jspui/handle/123456789/19327
dc.rightsDefault Licence-
dc.subjectAdulten
dc.subjectAgeden
dc.subjectAntineoplastic Agents, Alkylating/administration & dosage/*adverseen
dc.subjecteffects/pharmacokineticsen
dc.subjectDose-Response Relationship, Drugen
dc.subjectDrug Administration Scheduleen
dc.subjectFemaleen
dc.subjectGlucose/analogs & derivativesen
dc.subjectHumansen
dc.subjectIfosfamide/analogs & derivativesen
dc.subjectInfusions, Intravenousen
dc.subjectMaleen
dc.subjectMiddle Ageden
dc.subjectMonosaccharide Transport Proteins/biosynthesis/*metabolismen
dc.subjectNeoplasms/drug therapy/*metabolismen
dc.subjectPhosphoramide Mustards/administration & dosage/*adverse effects/pharmacokineticsen
dc.titlePhase I trial of 6-hour infusion of glufosfamide, a new alkylating agent with potentially enhanced selectivity for tumors that overexpress transmembrane glucose transporters: a study of the European Organization for Research and Treatment of Cancer Early Clinical Studies Groupen
heal.abstractPURPOSE: To determine the maximum-tolerated dose (MTD), the principal toxicities, and the pharmacokinetics of 6-hour infusion of glufosfamide (beta-D-glucosylisophosphoramide mustard; D-19575), a novel alkylating agent with the potential to target the glucose transporter system. PATIENTS AND METHODS: Twenty-one patients (10 women and 11 men; median age, 56 years) with refractory solid tumors were treated with doses ranging from 800 to 6,000 mg/m(2). Glufosfamide was administered every 3 weeks as a two-step (fast/slow) intravenous infusion over a 6-hour period. All patients underwent pharmacokinetic sampling at the first course. RESULTS: The MTD was 6,000 mg/m(2). At this dose, two of six patients developed a reversible, dose-limiting renal tubular acidosis and a slight increase in serum creatinine the week after the second and third courses of treatment, respectively, whereas three of six patients experienced short-lived grade 4 neutropenia/leukopenia. Other side effects were generally mild. Pharmacokinetics indicated linearity of area under the time-versus-concentration curve against dose over the dose range studied and a short elimination half-life. There was clear evidence of antitumor activity, with a long-lasting complete response of an advanced pancreatic adenocarcinoma and minor tumor shrinkage of two refractory colon carcinomas and one heavily pretreated breast cancer. CONCLUSION: The principal toxicity of 6-hour infusion of glufosfamide is reversible renal tubular acidosis, the MTD is 6,000 mg/m(2), and the recommended phase II dose is 4, 500 mg/m(2). Close monitoring of serum potassium and creatinine levels is suggested for patients receiving glufosfamide for early detection of possible renal toxicity. Evidence of antitumor activity in resistant carcinomas warrants further clinical exploration of glufosfamide in phase II studies.en
heal.accesscampus-
heal.fullTextAvailabilityTRUE-
heal.identifier.secondaryhttp://www.ncbi.nlm.nih.gov/pubmed/11032596-
heal.journalNameJ Clin Oncolen
heal.journalTypepeer-reviewed-
heal.languageen-
heal.publicationDate2000-
heal.recordProviderΠανεπιστήμιο Ιωαννίνων. Σχολή Επιστημών Υγείας. Τμήμα Ιατρικήςel
heal.typejournalArticle-
heal.type.elΆρθρο Περιοδικούel
heal.type.enJournal articleen

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