Document Detail


Optimally tolerated dose of lapatinib in combination with docetaxel plus trastuzumab in first-line treatment of HER2-positive metastatic breast cancer.
MedLine Citation:
PMID:  23878115     Owner:  NLM     Status:  In-Data-Review    
Abstract/OtherAbstract:
BACKGROUND: This phase IB, open-label, dose-escalation study evaluated the safety, tolerability, and optimally tolerated regimen (OTR) of lapatinib in combination with docetaxel and trastuzumab in patients with previously untreated stage IV metastatic breast cancer (MBC) tumors overexpressing human epidermal growth factor receptor 2 (HER2).
PATIENTS AND METHODS: Evaluated dose regimens included lapatinib (500-1500 mg/day), docetaxel (triweekly; 60-100 mg/m²), and trastuzumab (weekly; 2 mg/kg fixed dose); prophylactic granulocyte colony-stimulating factor was included with regimens with ≥750 mg/day lapatinib. End points included OTR and safety/tolerability (primary), overall response rate (ORR), and pharmacokinetics (secondary).
RESULTS: None of the patients (N = 53) experienced dose-limiting toxic effects (DLTs) at the highest dose level; thus, the OTR of lapatinib with 100 mg/m(2) docetaxel was not determined. Common adverse events included diarrhea, nausea, alopecia, fatigue, and rash; grade 3/4 (≥2 patients) were neutropenia, diarrhea, leukopenia, peripheral neuropathy, and rash. Seven patients had DLTs (cycle 1). In 45 patients with measurable disease confirmed by bone scan, investigator-assessed ORR was 31%; without bone scan, confirmation was 64%; 8 patients without measurable disease were evaluated as stable. Lapatinib/docetaxel plasma concentrations were positively associated with complete response.
CONCLUSIONS: Lapatinib/docetaxel/trastuzumab is a feasible and well-tolerated treatment of untreated HER2-positive stage IV MBC. Two lapatinib/docetaxel OTR doses were recommended (1250 mg/75 mg/m²; 1000 mg/100 mg/m²).
CLINICAL TRIAL NUMBER: NCT00251433.
Authors:
J Crown; M J Kennedy; P Tresca; M Marty; M Espie; H A Burris; M Desilvio; M R Lau; D Kothari; K M Koch; V Diéras
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Annals of oncology : official journal of the European Society for Medical Oncology / ESMO     Volume:  24     ISSN:  1569-8041     ISO Abbreviation:  Ann. Oncol.     Publication Date:  2013 Aug 
Date Detail:
Created Date:  2013-07-23     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9007735     Medline TA:  Ann Oncol     Country:  England    
Other Details:
Languages:  eng     Pagination:  2005-11     Citation Subset:  IM    
Affiliation:
All Ireland Cooperative Oncology Research Group, Dublin, Ireland.
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