Atrasentan in Patients With Advanced Renal Cell Carcinoma: A Phase 2 Trial of the ECOG-ACRIN Cancer Research Group (E6800)

作者：Carducci Michael A; Manola Judith^*; Nair Suresh G; Liu Glenn; Rousey Steven; Dutcher Janice P; Wilding George

来源：Clinical Genitourinary Cancer, 2015, 13(6): 531-539.

DOI：10.1016/clgc.2015.07.002

• Bone metastases
• Endothelin A receptor antagonist
• Kidney cancer
• Pain palliation
• Progression-free survival

The use of atrasentan, an endothelin receptor A antagonist, was studied in cohorts of patients with renal cell carcinoma (RCC) with and without prior immunotherapy and either measurable disease or bone metastases only in the pre-VEGF/TKI era. Although well tolerated, atrasentan did not yield 6-month progression-free rates supporting its use as first-line monotherapy in patients with advanced RCC.
Background: Atrasentan, an oral endothelin receptor A antagonist, demonstrated phase 1 activity in patients with renal cell carcinoma (RCC). A phase 2 study was undertaken in patients with measurable or bone-only metastatic RCC in the pre-VEGF/TKI era. Methods and Materials: Patients were stratified by disease status and prior immunotherapy. Eligible patients had no prior chemotherapy, 0 to 1 prior immunotherapies, and an Eastern Cooperative Oncology Group performance status of 0 to 2. Patients received atrasentan 10 mg per day until progression. The primary end point was progression-free (PF) rate at 6 months. Rates of 25% among patients treated with prior immunotherapy and 45% among patients with no prior immunotherapy were considered promising. A 2-stage design was used for cohorts without prior immunotherapy. Results: From 2003 to 2005, 98 patients were registered. Median treatment duration was 9.9 weeks (range, 0.3-107 weeks). Toxicities were mild; 71% of patients reported no grade 3 or higher treatment-related events. Grade 4 events included neutropenia (n = 3), dyspnea (n = 2), thrombosis (n = 1), and arrhythmia (n = 1). Two grade 5 events (dyspnea and constitutional) were possibly treatment related. Six-month PF rates (90% confidence interval) were 14% (6-25), 0% (0-39), 8% (1-23), and 22% (8-44), respectively, for patients with prior immunotherapy/measurable disease (n = 44), prior immunotherapy/bone metastases (n = 6), no prior immunotherapy/measurable disease (n = 25), and no prior immunotherapy/bone metastases (n = 18). Median PF survival was 2.3 months (95% confidence interval, 2.0-3.5 months). Conclusion: Although well tolerated, atrasentan did not yield 6-month PF rates supporting its use as first-line monotherapy in patients with advanced RCC.

• 出版日期2015-12
• 单位河北医科大学