Phase 1 dose escalation study of rigosertib by 2-, 4-, or 8-hour infusion twice-weekly in patients with advanced cancer.

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dc.contributor.authorAdvani, S H
dc.contributor.authorAchrekar, S D
dc.contributor.authorDoval, D C
dc.contributor.authorRaghunadharao, D
dc.contributor.authorWilhelm, F E
dc.contributor.authorAcharya, M
dc.date.accessioned2014-12-29T10:36:21Z
dc.date.available2014-12-29T10:36:21Z
dc.date.issued2014-01
dc.description.abstractCONTEXT: Rigosertib, a potent, multi-kinase inhibitor that selectively induces mitotic arrest and apoptosis in cancer cells and is non-toxic to normal cells, is being developed for the treatment of solid tumors and hematological malignancies. AIMS: To determine the safety, doselimiting toxicities, and clinical activity of rigosertib administered by 2-, 4-, or 8-hour continuous IV infusion twice-a-week for 3 weeks out of a 4-week cycle in patients with advanced solid tumor or hematological malignancies; and to confirm the safety and tolerability of the recommended phase 2 dose (RPTD). SETTINGS AND DESIGN: Phase 1, open-label, dose-escalation study in men and women ≥18 years of age. MATERIALS AND METHODS: An escalation phase optimized the duration of infusion (2, 4, or 8 hours) of 3200 mg rigosertib twice-a-week for 3 weeks of a 4-week cycle; an expansion phase confirmed the maximum tolerated dose (MTD). STATISTICAL ANALYSIS USED: All data summaries were descriptive. PK parameters were estimated using compartmental analysis. RESULTS: 25 patients (16 male, 9 female, 26- 66 years, all Asian) were treated with rigosertib, 16 in the escalation phase; 9 in the expansion phase. MTD was determined to be 3200 mg as a 4-hour infusion and 2400 mg over 4 hours was declared to be the RPTD. Best response was stable disease in 5 of 14 evaluable patients, with a mean (range) of 90 (43-108) days. CONCLUSIONS: 2400 mg rigosertib as a 4-hour infusion was identified as the RPTD. Five patients achieved stable disease lasting 6-16 weeks.en_US
dc.identifier.citationAdvani S H, Achrekar S D, Doval D C, Raghunadharao D, Wilhelm F E, Acharya M. Phase 1 dose escalation study of rigosertib by 2-, 4-, or 8-hour infusion twice-weekly in patients with advanced cancer. Indian Journal of Cancer. 2014 Jan-Mar; 51(1): 40-44.en_US
dc.identifier.urihttps://imsear.searo.who.int/handle/123456789/154282
dc.language.isoenen_US
dc.source.urihttps://www.indianjcancer.com/article.asp?issn=0019-509X;year=2014;volume=51;issue=1;spage=40;epage=44;aulast=Advanien_US
dc.subjectRigosertiben_US
dc.subjectpharmacokineticsen_US
dc.subjectovarianen_US
dc.subjectpancreaticen_US
dc.subjectresponse evaluation criteria in solid tumoren_US
dc.subjecteastern cooperative oncology groupen_US
dc.subjectdose-escalationen_US
dc.subject.meshAdult
dc.subject.meshAged
dc.subject.meshAntineoplastic Agents --administration & dosage
dc.subject.meshAntineoplastic Agents --pharmacokinetics
dc.subject.meshCohort Studies
dc.subject.meshDose-Response Relationship, Drug
dc.subject.meshFemale
dc.subject.meshFollow-Up Studies
dc.subject.meshGlycine --administration & dosage
dc.subject.meshGlycine --analogs & derivatives
dc.subject.meshGlycine --pharmacokinetics
dc.subject.meshHumans
dc.subject.meshInfusions, Intravenous
dc.subject.meshMale
dc.subject.meshMaximum Tolerated Dose
dc.subject.meshMiddle Aged
dc.subject.meshNeoplasm Staging
dc.subject.meshNeoplasms --drug therapy
dc.subject.meshNeoplasms --metabolism
dc.subject.meshNeoplasms --pathology
dc.subject.meshPrognosis
dc.subject.meshSulfones --administration & dosage
dc.subject.meshSulfones --pharmacokinetics
dc.subject.meshTime Factors
dc.subject.meshTissue Distribution
dc.titlePhase 1 dose escalation study of rigosertib by 2-, 4-, or 8-hour infusion twice-weekly in patients with advanced cancer.en_US
dc.typeArticleen_US
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