TY - JOUR
T1 - Atrasentan in patients with advanced renal cell carcinoma
T2 - A phase 2 trial of the ECOG-ACRIN cancer research group (E6800)
AU - Carducci, Michael A.
AU - Manola, Judith
AU - Nair, Suresh G.
AU - Liu, Glenn
AU - Rousey, Steven
AU - Dutcher, Janice P.
AU - Wilding, George
N1 - Funding Information:
This study was coordinated by the ECOG-ACRIN Cancer Research Group (Robert L. Comis, MD, and Mitchell D. Schnall, MD, PhD, Group Co-Chairs) and was supported in part by Public Health Service grants CA180794 , CA180820 , CA180802 , CA180799 , CA189863 , and CA189859 from the National Cancer Institute , National Institutes of Health , Department of Health and Human Services . The investigational agent for the study was provided by Abbott Inc. This article's content is solely the responsibility of the authors and does not necessarily represent the official views of the National Cancer Institute.
Publisher Copyright:
© 2015 Elsevier Inc. All rights reserved.
PY - 2015/12
Y1 - 2015/12
N2 - 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.
AB - 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.
KW - Bone metastases
KW - Endothelin A receptor antagonist
KW - Kidney cancer
KW - Pain palliation
KW - Progression-free survival
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U2 - 10.1016/j.clgc.2015.07.002
DO - 10.1016/j.clgc.2015.07.002
M3 - Article
C2 - 26272427
AN - SCOPUS:84947863300
SN - 1558-7673
VL - 13
SP - 531-539.e1
JO - Clinical Genitourinary Cancer
JF - Clinical Genitourinary Cancer
IS - 6
ER -