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dc.contributor.authorde Jonge, MJAen_US
dc.contributor.authorPunt, CJAen_US
dc.contributor.authorSparreboom, Aen_US
dc.contributor.authorPlanting, ASTen_US
dc.contributor.authorPeters, MEWJen_US
dc.contributor.authorvan de Schraaf, Jen_US
dc.contributor.authorJackman, Aen_US
dc.contributor.authorSmith, Ren_US
dc.contributor.authorde Mulder, PHMen_US
dc.contributor.authorVerweij, Jen_US
dc.date.accessioned2018-09-18T14:41:48Z
dc.date.issued2002-04-01en_US
dc.identifier7en_US
dc.identifier.citationJOURNAL OF CLINICAL ONCOLOGY, 2002, 20 pp. 1923 - 1931en_US
dc.identifier.issn0732-183Xen_US
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/2793
dc.identifier.doi10.1200/JCO.2002.07.057en_US
dc.description.abstractPurpose: To assess the toxicity profile and dose-limiting toxicities (DLTs), to determine the maximum-tolerated dose, and to study the pharmacokinetics of ZD9331 when administered orally to patients with advanced solid tumors. Patients and Methods: Patients were treated with oral ZD9331 given once daily (od) or twice daily (bid) for 5, 7, or 10 days; cycles were repeated every 21 days at doses ranging from 2.5 to 40 mg. For pharmacokinetic analysis, plasma sampling was performed during the first course and assayed using a validated liquid chromatographic-tandem mass spectrometry assay. Plasma levels of 2’-deoxyuridine were measured as a surrogate marker for TS inhibition. Results: Forty-two patients received a total of 166 courses. The DLTs were myelosuppression and skin rash. Dose escalation of oral ZD9331 from 2.5 to 40 mg, as a single daily dose, resulted in a less than proportional increase in the plasma area under the concentration-time curve of ZD9331. The plasma drug exposure per cycle for the schedules 20 mg ad for 5 days, 10 mg ad for 10 days, and 10 mg bid for 5 days, all resulting in a total dose per cycle of 100 mg, were comparable. One partial response was noted in a patient with gastric cancer. Conclusion: DLTs in this phase I study of oral ZD9331 were myelosuppression and skin toxicity. The recommended dose for phase 11 studies of oral ZD9331 is 20 ring od for 5 consecutive days, every 3 weeks.en_US
dc.format.extent1923 - 1931en_US
dc.titlePhase I and pharmacologic study of oral ZD9331, a novel nonpolyglutamated thymidylate synthase inhibitor, in adult patients with solid tumorsen_US
dc.typeJournal Article
rioxxterms.versionofrecord10.1200/JCO.2002.07.057en_US
rioxxterms.licenseref.startdate2002-04-01en_US
rioxxterms.typeJournal Article/Reviewen_US
dc.relation.isPartOfJOURNAL OF CLINICAL ONCOLOGYen_US
pubs.notesresearcherid-numbers: Peters, M.E.W.J./L-4574-2015 Sparreboom, Alex/B-3247-2008 unique-id: ISI:000174845200031en_US
pubs.notesNot knownen_US
pubs.organisational-group/ICR
pubs.volume20en_US
pubs.embargo.termsNot knownen_US
dc.contributor.icrauthorJackman, Annen_US


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