A Phase II Study of Vaginal Testosterone Cream (TEST) vs. Estring for Vaginal Dryness or Decreased Libido in Women with Early Stage Breast Cancer (BC) Treated with Aromatase Inhibitors (AIs).

Abstract

Abstract Background: Sexual issues including vaginal dryness and decreased libido are common among breast cancer patients. Many interventions are hormonally based. The risk of these treatments is unknown and is of interest, particularly for patients with hormone receptor positive disease. Design: In a randomized open label study, we are evaluating the safety, based on serial measurements of serum estradiol (E) levels, of intravaginal TEST or Estring used for 12 weeks (wks) for relief of vaginal dryness and/or decreased libido in women with early stage BC taking AIs. Planned enrollment is 35 patients (pts) per arm, and accrual will stop if a predetermined number of pts has a sustained elevation in serum E while on study. E is measured by an ultrasensensitive liquid chromatography-tandem mass spectrometry based assay. Eligible pts have not had a menstrual period for 12 months. and have taken an AI for at least one month. Pts who received chemotherapy or who are on ovarian suppression must have a serum E of <10 pg/ml during the screening period. Pts are randomized to Estring 2mg for 12 wks or TEST inserted vaginally at a dose of 0.5 grams daily for 2 wks and then three times a week for 10 wks. Pts undergo a gynecologic exam at baseline and at wk 12 to score vaginal atrophy including measures of rugae, dryness, pallor, petachiae, and mucosal thinning. Serum E levels and a validated sexual quality of life questionnaire are collected at baseline, then at wks 4 and 12. Pts randomized to TEST have serum testosterone drawn at the same time points. Serum E levels are repeated at wk 8 and/or wk 16 if the level is elevated at either wk 4 or wk 12 to > 10 pg/ml or if there is a > 10 pg/ml elevation above their baseline value.Results: 29 pts have been enrolled; 15 to TEST, 14 to Estring. 20 pts have completed the 12 wk study period. Adverse events are rare and include grade 1 vaginal discharge, odor, or burning, and hair growth. Two pts did not complete the study due to the Estring falling out. One pt discontinued Estring due to vaginal discharge and irritation. One pt using TEST discontinued treatment due to a herpes outbreak. Among the Estring pts, two had an elevation in serum E to >10 pg/ml (14 pg/ml and 70 pg/ml) at wk 4 or at wk 12; but E returned to <10 pg/ml 4 wks later. Among pts using TEST, four had an elevation of serum E to > 10pg/ml at wk 4 or at wk 12; one remained modestly elevated (17 pg/ml) 4 wks later. Vaginal atrophy scores showed improvement in pts receiving both treatments, although the study is not powered to show a difference between the two arms.Conclusions: Both vaginal TEST and Estring appear to be effective options to treat vaginal dryness in pts with early stage BC on AIs. The number of pts with sustained elevations in serum E levels to date has not reached the pre-defined threshold for stopping the study. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 5038.