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dc.contributor.authorGore, ME
dc.contributor.authorJones, RJ
dc.contributor.authorRavaud, A
dc.contributor.authorKuczyk, M
dc.contributor.authorDemkow, T
dc.contributor.authorBearz, A
dc.contributor.authorShapiro, J
dc.contributor.authorStrauss, UP
dc.contributor.authorPorta, C
dc.date.accessioned2017-04-19T08:54:13Z
dc.date.issued2017-06
dc.identifier.citationBJU international, 2017, 119 (6), pp. 846 - 853
dc.identifier.issn1464-4096
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/606
dc.identifier.eissn1464-410X
dc.identifier.doi10.1111/bju.13740
dc.description.abstractObjective To assess the efficacy and safety of sorafenib dose escalation in metastatic renal cell carcinoma (mRCC).Patients and methods Intra-patient dose escalation may enhance the clinical benefit of targeted anticancer agents in metastatic disease. In this non-randomised, open-label, Phase 2b study, treatment-naïve patients with mRCC were initially treated with the standard oral sorafenib dose [400 mg twice daily (BID)]. Two dose escalations were planned, each 200 mg BID after 28 days at the prior level. Dose reductions, interruptions, or delayed escalations were used to manage adverse events (AEs). The primary endpoint was objective response rate (ORR) in the modified intent-to-treat (mITT) population, which comprised patients with ≥6 months of treatment including ≥4 months of therapy at their highest tolerated dose. Secondary endpoints included progression-free survival (PFS) and safety.Results In all, 83 patients received sorafenib. The dose received for the longest duration was 400, 600, and 800 mg BID in 48.2%, 15.7%, and 24.1% of patients, respectively. The ORR was 44.4% [n = 8/18; 95% confidence interval (CI) 21.5-69.2] and 17.9% (n = 12/67; 95% CI 9.6-29.2) in the mITT and ITT populations, respectively. The median (95% CI) PFS was 7.4 (6.0-11.7) months (ITT). The most common AEs of any grade were hand-foot skin reaction (66.3%) and diarrhoea (63.9%).Conclusion Sorafenib demonstrated clinical benefit in treatment-naïve patients with mRCC. However, relatively few patients could sustain doses of >400 mg BID. There was evidence that, where tolerated, escalation from the standard sorafenib dose may have enhanced clinical benefit. However, this study does not support dose escalation for most patients with treatment-naïve mRCC. Alternative protocols for sorafenib dose escalation could be explored.
dc.formatPrint-Electronic
dc.format.extent846 - 853
dc.languageeng
dc.language.isoeng
dc.rights.urihttps://www.rioxx.net/licenses/all-rights-reserved
dc.subjectHumans
dc.subjectCarcinoma, Renal Cell
dc.subjectKidney Neoplasms
dc.subjectPhenylurea Compounds
dc.subjectNiacinamide
dc.subjectAntineoplastic Agents
dc.subjectDisease-Free Survival
dc.subjectTreatment Outcome
dc.subjectResearch Design
dc.subjectAdult
dc.subjectAged
dc.subjectAged, 80 and over
dc.subjectMiddle Aged
dc.subjectFemale
dc.subjectMale
dc.subjectSorafenib
dc.titleSorafenib dose escalation in treatment-naïve patients with metastatic renal cell carcinoma: a non-randomised, open-label, Phase 2b study.
dc.typeJournal Article
rioxxterms.versionofrecord10.1111/bju.13740
rioxxterms.licenseref.urihttps://www.rioxx.net/licenses/all-rights-reserved
rioxxterms.licenseref.startdate2017-06
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfBJU international
pubs.issue6
pubs.notes12 months
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/Royal Marsden Clinical Units
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/Royal Marsden Clinical Units
pubs.publication-statusPublished
pubs.volume119
pubs.embargo.terms12 months
dc.contributor.icrauthorGore, Martinen
dc.contributor.icrauthorMarsden,en


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