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dc.contributor.authorSpicer, J
dc.contributor.authorIrshad, S
dc.contributor.authorAng, JE
dc.contributor.authorEnting, D
dc.contributor.authorKristeleit, R
dc.contributor.authorUttenreuther-Fischer, M
dc.contributor.authorPemberton, K
dc.contributor.authorPelling, K
dc.contributor.authorSchnell, D
dc.contributor.authorde Bono, J
dc.date.accessioned2016-12-12T14:05:03Z
dc.date.issued2017-01
dc.identifier.citationCancer chemotherapy and pharmacology, 2017, 79 (1), pp. 17 - 27
dc.identifier.issn0344-5704
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/329
dc.identifier.eissn1432-0843
dc.identifier.doi10.1007/s00280-016-3189-1
dc.description.abstractPurpose The combination of afatinib, an irreversible ErbB family blocker, with paclitaxel and bevacizumab was assessed in patients with advanced solid tumors.Methods This phase I study used a 3 + 3 design to determine the maximum tolerated dose (MTD) of afatinib combined with paclitaxel and bevacizumab. Safety, pharmacokinetics, and anti-tumor activity were also assessed. The starting dose was oral afatinib 40 mg once daily plus intravenous paclitaxel (fixed dose 80 mg/m 2 , Days 1, 8, and 15 of a 4-week cycle) and intravenous bevacizumab 5 mg/kg every 2 weeks.Results Twenty-nine patients were enroled. The afatinib dose was de-escalated to 30 mg and then 20 mg after 2/6 and 2/5 evaluable patients developed dose-limiting toxicities at 40 and 30 mg, respectively, when combined with paclitaxel and bevacizumab 5 mg/kg. The bevacizumab dose was subsequently escalated to 10 mg/kg, and MTD was defined as afatinib 20 mg plus paclitaxel 80 mg/m 2 and bevacizumab 10 mg/kg. Frequent (any grade) treatment-related adverse events (AEs) included diarrhea (83%), rash/acne (83%), fatigue (79%), mucosal inflammation (59%), and nausea (59%). Based on overall safety, bevacizumab was amended to 7.5 mg/kg for the recommended phase II dose. Pharmacokinetic analyses suggested no relevant drug-drug interactions. Three (10%) confirmed partial responses were observed; 15 (52%) patients had stable disease.Conclusions The recommended phase II dose schedule was afatinib 20 mg/day with paclitaxel 80 mg/m 2 (Days 1, 8, and 15 every 4 weeks) and bevacizumab 7.5 mg/kg every 2 weeks. At this dose schedule, AEs were manageable, and anti-tumor activity was observed.
dc.formatPrint-Electronic
dc.format.extent17 - 27
dc.languageeng
dc.language.isoeng
dc.rights.urihttps://creativecommons.org/licenses/by/4.0
dc.subjectHumans
dc.subjectNeoplasms
dc.subjectPaclitaxel
dc.subjectQuinazolines
dc.subjectAntineoplastic Combined Chemotherapy Protocols
dc.subjectMaximum Tolerated Dose
dc.subjectAdult
dc.subjectAged
dc.subjectMiddle Aged
dc.subjectFemale
dc.subjectMale
dc.subjectBevacizumab
dc.subjectAfatinib
dc.titleA phase I study of afatinib combined with paclitaxel and bevacizumab in patients with advanced solid tumors.
dc.typeJournal Article
dcterms.dateAccepted2016-10-31
rioxxterms.versionofrecord10.1007/s00280-016-3189-1
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0
rioxxterms.licenseref.startdate2017-01
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfCancer chemotherapy and pharmacology
pubs.issue1
pubs.notesNo embargo
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies/Prostate Cancer Targeted Therapy 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/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies/Prostate Cancer Targeted Therapy Group
pubs.organisational-group/ICR/Primary Group/Royal Marsden Clinical Units
pubs.publication-statusPublished
pubs.volume79
pubs.embargo.termsNo embargo
icr.researchteamProstate Cancer Targeted Therapy Groupen_US
dc.contributor.icrauthorDe Bono, Johannen
dc.contributor.icrauthorMarsden,en


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