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dc.contributor.authorJerusalem, G
dc.contributor.authorFasolo, A
dc.contributor.authorDieras, V
dc.contributor.authorCardoso, F
dc.contributor.authorBergh, Jonas
dc.contributor.authorVittori, L
dc.contributor.authorZhang, Y
dc.contributor.authorMassacesi, C
dc.contributor.authorSahmoud, T
dc.contributor.authorGianni, L
dc.date.accessioned2011-12-05T13:55:07Z
dc.date.available2011-12-05T13:55:07Z
dc.date.issued2011-01
dc.identifier.citationPhase I trial of oral mTOR inhibitor everolimus in combination with trastuzumab and vinorelbine in pre-treated patients with HER2-overexpressing metastatic breast cancer. 2011, 125 (2):447-55 Breast Cancer Res Treaten
dc.identifier.issn1573-7217
dc.identifier.pmid21107682
dc.identifier.doi10.1007/s10549-010-1260-x
dc.identifier.urihttp://hdl.handle.net/10541/193229
dc.description.abstractTo determine the feasible dose and schedule for everolimus, an oral mTOR inhibitor, combined with vinorelbine and trastuzumab for patients with HER2-overexpressing metastatic breast cancer pretreated with trastuzumab. In this phase Ib multicenter, Bayesian dose-escalation study, 50 patients received everolimus 5 mg/day, 20 mg/week, or 30 mg/week plus vinorelbine (25 mg/m² on day 1 and 8 every 3 weeks) and trastuzumab (2 mg/kg weekly). Endpoints included end-of-cycle-1 dose-limiting toxicity (DLT) rate (primary endpoint), safety, relative dose intensity, overall response rate (ORR), and pharmacokinetics. Grade 3/4 neutropenia was the most common end-of-cycle-1 DLT and occurred in 10 of 30 and 4 of 14 patients in the 5 mg/day and 30 mg/week cohorts, respectively. Other end-of-cycle-1 DLTs included single cases of febrile neutropenia, grade 3 stomatitis with concomitant fatigue, grade 2 stomatitis, grade 3 anorexia, and grade 2 acneiform dermatitis, all in the 5-mg/day cohort. Based on the recorded DLTs and global safety, everolimus 5 mg/day and 30 mg/week were chosen as the optimal dose levels for the daily and weekly arms. Forty-seven patients were evaluable for efficacy. ORR was 19.1%, with a disease control rate of 83.0% and median progression-free survival of 30.7 weeks. No drug interaction was observed between everolimus and vinorelbine. Everolimus combined with weekly vinorelbine and trastuzumab generally was well tolerated and had encouraging antitumor activity in heavily pretreated patients with HER2-overexpressing metastatic breast cancer that progressed on trastuzumab (NCT00426530).
dc.language.isoenen
dc.subject.meshAdult
dc.subject.meshAged
dc.subject.meshAntibodies, Monoclonal
dc.subject.meshAntineoplastic Combined Chemotherapy Protocols
dc.subject.meshBreast Neoplasms
dc.subject.meshDisease-Free Survival
dc.subject.meshDrug Administration Schedule
dc.subject.meshFemale
dc.subject.meshGenes, erbB-2
dc.subject.meshHumans
dc.subject.meshMiddle Aged
dc.subject.meshNeoplasm Metastasis
dc.subject.meshPrognosis
dc.subject.meshSirolimus
dc.subject.meshSurvival Analysis
dc.subject.meshTOR Serine-Threonine Kinases
dc.subject.meshTreatment Outcome
dc.subject.meshVinblastine
dc.titlePhase I trial of oral mTOR inhibitor everolimus in combination with trastuzumab and vinorelbine in pre-treated patients with HER2-overexpressing metastatic breast cancer.en
dc.typeArticleen
dc.contributor.departmentCHU Sart-Tilman, Liège, Belgium.en
dc.identifier.journalBreast Cancer Research and Treatmenten
html.description.abstractTo determine the feasible dose and schedule for everolimus, an oral mTOR inhibitor, combined with vinorelbine and trastuzumab for patients with HER2-overexpressing metastatic breast cancer pretreated with trastuzumab. In this phase Ib multicenter, Bayesian dose-escalation study, 50 patients received everolimus 5 mg/day, 20 mg/week, or 30 mg/week plus vinorelbine (25 mg/m² on day 1 and 8 every 3 weeks) and trastuzumab (2 mg/kg weekly). Endpoints included end-of-cycle-1 dose-limiting toxicity (DLT) rate (primary endpoint), safety, relative dose intensity, overall response rate (ORR), and pharmacokinetics. Grade 3/4 neutropenia was the most common end-of-cycle-1 DLT and occurred in 10 of 30 and 4 of 14 patients in the 5 mg/day and 30 mg/week cohorts, respectively. Other end-of-cycle-1 DLTs included single cases of febrile neutropenia, grade 3 stomatitis with concomitant fatigue, grade 2 stomatitis, grade 3 anorexia, and grade 2 acneiform dermatitis, all in the 5-mg/day cohort. Based on the recorded DLTs and global safety, everolimus 5 mg/day and 30 mg/week were chosen as the optimal dose levels for the daily and weekly arms. Forty-seven patients were evaluable for efficacy. ORR was 19.1%, with a disease control rate of 83.0% and median progression-free survival of 30.7 weeks. No drug interaction was observed between everolimus and vinorelbine. Everolimus combined with weekly vinorelbine and trastuzumab generally was well tolerated and had encouraging antitumor activity in heavily pretreated patients with HER2-overexpressing metastatic breast cancer that progressed on trastuzumab (NCT00426530).


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