dc.contributor.author | Spicer, J | |
dc.contributor.author | Irshad, S | |
dc.contributor.author | Ang, JE | |
dc.contributor.author | Enting, D | |
dc.contributor.author | Kristeleit, R | |
dc.contributor.author | Uttenreuther-Fischer, M | |
dc.contributor.author | Pemberton, K | |
dc.contributor.author | Pelling, K | |
dc.contributor.author | Schnell, D | |
dc.contributor.author | de Bono, J | |
dc.date.accessioned | 2016-12-12T14:05:03Z | |
dc.date.issued | 2017-01-01 | |
dc.identifier.citation | Cancer chemotherapy and pharmacology, 2017, 79 (1), pp. 17 - 27 | |
dc.identifier.issn | 0344-5704 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/329 | |
dc.identifier.eissn | 1432-0843 | |
dc.identifier.doi | 10.1007/s00280-016-3189-1 | |
dc.description.abstract | PURPOSE: 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/m2, 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/m2 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/m2 (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.format | Print-Electronic | |
dc.format.extent | 17 - 27 | |
dc.language | eng | |
dc.language.iso | eng | |
dc.publisher | SPRINGER | |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0 | |
dc.subject | Humans | |
dc.subject | Neoplasms | |
dc.subject | Paclitaxel | |
dc.subject | Quinazolines | |
dc.subject | Antineoplastic Combined Chemotherapy Protocols | |
dc.subject | Maximum Tolerated Dose | |
dc.subject | Adult | |
dc.subject | Aged | |
dc.subject | Middle Aged | |
dc.subject | Female | |
dc.subject | Male | |
dc.subject | Bevacizumab | |
dc.subject | Afatinib | |
dc.title | A phase I study of afatinib combined with paclitaxel and bevacizumab in patients with advanced solid tumors. | |
dc.type | Journal Article | |
dcterms.dateAccepted | 2016-10-31 | |
rioxxterms.versionofrecord | 10.1007/s00280-016-3189-1 | |
rioxxterms.licenseref.uri | https://creativecommons.org/licenses/by/4.0 | |
rioxxterms.licenseref.startdate | 2017-01 | |
rioxxterms.type | Journal Article/Review | |
dc.relation.isPartOf | Cancer chemotherapy and pharmacology | |
pubs.issue | 1 | |
pubs.notes | No 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-status | Published | |
pubs.volume | 79 | |
pubs.embargo.terms | No embargo | |
icr.researchteam | Prostate Cancer Targeted Therapy Group | |
dc.contributor.icrauthor | De Bono, Johann | |