Phase II trial of anastrozole in women with asymptomatic mullerian cancer

Objective. To evaluate the efficacy and toxicity of the selective aromatase inhibitor anastrozole (Arimidex), we conducted a phase 11 trial in 53 women with asymptomatic recurrent/persistent mullerian cancer. Methods. Patients with ovarian, peritoneal, or fallopian tube carcinoma were eligible for enrollment. Eligible patients had an ECOG PS :! I and no clinical indication for immediate systemic chemotherapy. Patients were assigned to measurable (cohort 1) or evaluable disease (cohort 2) cohorts, respectively. Patients were treated with anastrozole I mg po daily. Monthly follow-up included interim history, physical exam, and CA-125 with radiologic evaluation every 3 months. Estrogen, progesterone, and Her-2/neu receptor status was also evaluated in archived tumor samples. Results. Fifty-three women with a median age of 63 (range, 46-86) years were enrolled. Twenty-nine women enrolled in cohort I and 24 in cohort 2. Included were 43, 7, and 3 women with ovarian, primary peritoneal, and fallopian tube carcinoma, respectively. All 53 patients were evaluable for treatment toxicity and response. The median time to disease progression was 85 days (85 days for cohort I and 82 days for cohort 2). A partial response was documented in a single patient with measurable disease. Forty-two percent of patients had stable disease (measured as time to treatment termination) for >90 days, 15% for >180 days, 7% for >270 days, and 4% for >360 days. One patient remained on anastrozole at 15 months. Toxicity was modest (grade 1) and infrequent, with the most common toxicities being fatigue and hot flashes. There were no thrombotic complications. Median time to progression for patients with estrogen receptor-positive tumors was 72 days as compared to 125 days for those with tumors negative for the estrogen receptor (P = 0.95, log-rank test). The median time to progression in patients with progesterone-positive tumors was 77 days and 91 days for patients with progesterone-negative tumors. Conclusion. In summary, anastrozole is a well-tolerated oral agent but with minimal tumoricidal activity in women with recurrent/persistent mullerian cancers. A minority of patients demonstrated prolonged stable disease while on this agent. (C) 2003 Elsevier Inc. All rights reserved.