6533b826fe1ef96bd1283e36
RESEARCH PRODUCT
Phase IB study of the EpCAM antibody adecatumumab combined with docetaxel in patients with epcampositive relapsed or refractory advanced-stage breast cancer
D. RuttingerG. SchlimokMartin SchulerWolfgang EiermannGünther G. StegerA. LangMartin SebastianC. WolfP.a. BaeuerleG. GöppelNorbert MarschnerMartina SchmidtA. WolfClaus HanuschD. Oruziosubject
OncologyAdultmedicine.medical_specialtyMedizinBreast NeoplasmsDocetaxelAntibodies Monoclonal HumanizedDrug Administration ScheduleBreast cancerAdecatumumabLeukocytopeniaAntigens NeoplasmInternal medicineAntineoplastic Combined Chemotherapy ProtocolsmedicineHumansAgedbusiness.industryLiver NeoplasmsAntibodies MonoclonalHematologyMiddle Agedmedicine.diseaseEpithelial Cell Adhesion MoleculeMetastatic breast cancerSurgeryTreatment OutcomeOncologyDocetaxelTolerabilityResponse Evaluation Criteria in Solid TumorsDrug Resistance NeoplasmFemaleTaxoidsBreast diseaseNeoplasm Recurrence LocalbusinessCell Adhesion MoleculesLeukocyte Disordersmedicine.drugdescription
Background: Targeted therapy options in HER2-negative breast cancer are limited. This open-label, multicenter phase IB dose-escalation trial was conducted to determine safety, tolerability, and antitumor activity of a combination of docetaxel (Taxotere) and increasing doses of adecatumumab, a human IgG1 antibody targeting epithelial cell adhesion molecule (EpCAM), in EpCAM-positive relapsed or primary refractory advanced-stage breast cancer. Patients and methods: Patients pretreated with up to four prior chemotherapy regimens received increasing adecatumumab doses either every 3 weeks (q3w) or weekly (qw) combined with docetaxel (100 mg/m 2 q3w). Primary end points were safety and tolerability. Antitumor activity was evaluated according to RECIST. Clinical benefit was defined as complete or partial response or stable disease for ‡24 weeks. Results: Thirty-one evaluable patients were treated. Most adverse events were mild to moderate in severity. Neutropenia, leukocytopenia, lymphopenia, and diarrhea (dose-limiting) were the most frequent toxic effects. Maximum tolerated doses of adecatumumab given in combination with docetaxel were 550 mg/m 2 q3w and 360 mg/ m 2 qw. Clinical benefit was observed in 44% of patients treated with q3w adecatumumab and docetaxel, increasing to 63% in patients with high EpCAM-expressing tumors. Conclusion: Combination therapy of adecatumumab and docetaxel is safe, feasible, and potentially active in heavily pretreated advanced-stage breast cancer.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2012-09-01 |