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dc.contributor.authorSaran, Frank
dc.contributor.authorWelsh, Liam
dc.contributor.authorJames, Allan
dc.contributor.authorMcBain, Catherine
dc.contributor.authorGattamaneni, Rao
dc.contributor.authorJefferies, Sarah
dc.contributor.authorHarris, Fiona
dc.contributor.authorPemberton, Karine
dc.contributor.authorSchaible, Jennifer
dc.contributor.authorBender, Shaun
dc.contributor.authorCseh, Agnieszka
dc.contributor.authorBrada, Michael
dc.date.accessioned2021-12-24T14:37:18Z
dc.date.available2021-12-24T14:37:18Z
dc.date.issued2021-12
dc.date.submitted2021-08-03
dc.identifier.issn0167-594X
dc.identifier.others11060-021-03877-6
dc.identifier.other3877
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/331803
dc.descriptionFunder: Boehringer Ingelheim; doi: http://dx.doi.org/10.13039/100001003
dc.description.abstractBACKGROUND: Glioblastoma multiforme (GBM) is the most common primary malignant brain tumor in adults. Amplification or overexpression of the epidermal growth factor receptor gene, part of the ErbB family, occur in approximately 40% and 60% of patients with GBM, respectively. We present data from a dose-finding study of the ErbB inhibitor afatinib in combination with radiotherapy (RT), with or without temozolomide (TMZ), in patients with GBM. METHODS: This was a phase I, open-label, 3 + 3 dose-escalation trial in patients with newly-diagnosed, histologically-confirmed grade 4 malignant glioma and proven O6-methylguanine-DNA methyltransferase gene promoter methylation status. The primary endpoint was the maximum tolerated dose (MTD) of continuous daily afatinib when given in combination with RT, with (regimen M) or without (regimen U) concomitant TMZ treatment. RESULTS: Fifty-five patients were enrolled; 36 received ≥ 1 dose of trial medication (regimen M, n = 20, regimen U, n = 16). Afatinib was discontinued by all patients during the study. Reasons for afatinib discontinuation (regimen M/U) included disease progression (45%/50%), dose-limiting toxicity (10%/0%), and other adverse events (AEs; 35%/38%). The most frequently reported AEs with either regimen were diarrhea and rash, with no new safety signals identified. The MTD was determined as afatinib 30 mg in combination with daily TMZ and RT, and afatinib 40 mg in combination with RT alone. CONCLUSIONS: This study identified the MTD for afatinib in combination with RT, with and without TMZ, in patients with GBM. Further studies of afatinib in patients with GBM are warranted and should be based on appropriate biomarker-based preselection. TRIAL REGISTRATION: NCT00977431 (first posted September 15, 2009).
dc.languageen
dc.publisherSpringer Science and Business Media LLC
dc.subjectClinical Study
dc.subjectNCT00977431
dc.subjectNCT
dc.subjectGlioblastoma
dc.subjectAfatinib
dc.subjectDose-escalation
dc.subjectTemozolomide
dc.subjectRadiotherapy
dc.titleAfatinib and radiotherapy, with or without temozolomide, in patients with newly diagnosed glioblastoma: results of a phase I trial.
dc.typeArticle
dc.date.updated2021-12-24T14:37:17Z
prism.endingPage317
prism.issueIdentifier3
prism.publicationNameJ Neurooncol
prism.startingPage307
prism.volume155
dc.identifier.doi10.17863/CAM.79252
dcterms.dateAccepted2021-10-13
rioxxterms.versionofrecord10.1007/s11060-021-03877-6
rioxxterms.versionVoR
rioxxterms.licenseref.urihttp://creativecommons.org/licenses/by/4.0/
dc.contributor.orcidSaran, Frank [0000-0002-3448-5064]
dc.identifier.eissn1573-7373
cam.issuedOnline2021-11-17


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