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


CONCLUSIONS
Although well tolerated, atrasentan did not yield 6-month PF rates supporting its use as first-line monotherapy in patients with advanced RCC.
Johns Hopkins Kimmel Cancer Center, Baltimore, MD.
Michael A
MA
Carducci
Department of Biostatistics & Computational Biology, Dana-Farber Cancer Institute, Boston, MA. Electronic address: jmanola@jimmy.harvard.edu.
Judith
J
Manola
Hematology/Oncology Associates, Lehigh Valley Hospital-Cedar Crest, Allentown, PA.
Suresh G
SG
Nair
University of Wisconsin Carbone Cancer Center, Wisconsin Institute for Medical Research, Madison, WI.
Glenn
G
Liu
Metro-Minnesota CCOP, Edina, MN.
Steven
S
Rousey
Our Lady of Mercy Cancer Center, New York Medical College, Bronx, NY.
Janice P
JP
Dutcher
University of Wisconsin Carbone Cancer Center, Madison, WI.
George
G
Wilding
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000077868:Atrasentan; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000556:secondary; D002292:Carcinoma, Renal Cell / Q000188:drug therapy*; D018572:Disease-Free Survival; D065128:Endothelin Receptor Antagonists / Q000008:administration & dosage* / Q000009:adverse effects; D005260:Female; D006801:Humans; D007680:Kidney Neoplasms / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D011759:Pyrrolidines / Q000008:administration & dosage* / Q000009:adverse effects; D016896:Treatment Outcome
D065128:Endothelin Receptor Antagonists; D011759:Pyrrolidines; D000077868:Atrasentan
Bone metastases; Endothelin A receptor antagonist; Kidney cancer; Pain palliation; Progression-free survival