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Phase II study of eribulin (E7389) in patients (pts) with advanced urothelial cancer (UC)—Final report: A California Cancer Consortium-led NCI/CTEP-sponsored trial.
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2010
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Renal PathologyRenal InflammationPhase Ii StudyPharmacotherapy—Final ReportMolecular PharmacologyRenal FunctionGenitourinary CancerPrior Neo/adjuvant ChemotherapyChronic Kidney DiseaseRenal PharmacologyRadiation OncologyMolecular OncologyCancer ResearchNormal CreatinineMedicineKidney FailureMicrotubulin ModulatorAdvanced Urothelial CancerRenal PathophysiologyCancer TreatmentPharmacologyUrologyOncologyNephrologyKidney Research
4539 Background: There is an unmet need for new agents in locally advanced and metastatic UC, particularly for pts with renal dysfunction. Microtubule directed agents (vincas, taxanes) have activity in UC. A prior first in human phase I study of eribulin, a microtubulin modulator derived from the black Pacific sea sponge toxin showed that eribulin/metabolites are minimally renally excreted (T. Synold, ASCO A2054, 2005). Encouraging activity was evident in UC. Here we report the results of a subsequent ph II study in advanced UC. Methods: The ph II component of this study accrued patients with normal creatinine or calculated CrCl ≥60mL/m, UC: any histological type and no prior cytotoxic therapy for advanced disease (neo/adjuvant allowed). Eribulin 1.4mg/m2 was given IV on d 1 & 8, q3weeks. Endpoints: response rate (RR) >20% was deemed interesting in a 2-stage design requiring ≥2 responses/21 pts to proceed to total 41 pts; PFS and OS. Results: 40 pts entered. Patient characteristics: histology: 35 with transitional, 3 adenocarcinoma, 1 squamous and 1 small cell. Median age: 67 yrs (37-87); Males: 68%; KPS ≥90% in 60%, ≤80% in 40%. Prior neo/adjuvant chemotherapy in 72.5%. Bajorin risk groups: 0: 30%, 1: 57%, 2: 13%. Three were inevaluable (2 off treatment due to toxicity and 1 early death). Overall RR was 38%, 95% CI: (23%, 54%) based on 37 evaluable pts with 1 CR +14 PR, 13/15 responses were in pts with TCC (RR 37% in subgroup). RR in pts with prior neo/adjuvant chemo: 34%. At median follow-up of 19.8 months, median PFS=3.9 months (2.7, 5.3; 36 pts progressed), median OS=9.4 mo (6.7, 11.9; 25 pts dead). PFS was associated with Bajorin risk group (p=0.028 for trend). Toxicities: 20 pts Gr 3/4 neutropenia, no febrile neutropenia, sensory neuropathy: 19 pts (18 Gr 1/2). Other non-hematologic toxicities: hyperglycemia (14, 3 Gr 3), hyponatremia (14, 4 Gr 3), alopecia (37), leg fatigue and aching (6, 1 Gr 3). Conclusions: E7389 has single agent activity in UC, even in pts with prior neo/adjuvant chemotherapy. Further evaluation of this agent in UC is warranted. Accrual is ongoing for pts with CrCl <40mL/m in whom the 1.4mg/m2 dose studied here is also tolerable (U01-CA062505). No significant financial relationships to disclose.