A multicenter randomized trial of DIAC for cyclical mastopathy

Cyclical mastopathy (CM) (ie, fibrocystic disease) is a commonly occurring condition with severe breast pain reportedly affecting up to 70% of women. DIAC is a new, non-hormonal treatment for CM that is administered as a capsule taken orally once each day. Earlier trials of DIAC have yielded promising results with resolution of the signs and symptoms of CM. We report the largest randomized clinical trial published to date on therapy for CM.Objective: To evaluate the safety and efficacy of different doses of DIAC compared to placebo given for 6 months to women with CM.Methods: A double-blind, randomized, dose-response, parallel-group clinical trial design was used. All enrolled women had moderate or severe cyclical mastalgia for at least 12 of the prior 24 months associated with nodularity and/or fibrosis on clinical exam. After obtaining informed consent, women were examined to exclude breast cancer or suspicious breast masses, thyroid disease, or other cancers. No one had recent breast surgery nor change in the use of hormones or adjuvant medication for breast pain for at least 3 months. A randomly generated number sequence was used to create a block randomization scheme. Women were assigned to receive either one of 5 daily doses of DIAC or placebo. One of the doses of DIAC was expected to be too low to provide relief of mastalgia. Women kept diary data daily. Clinical examinations and quality-of-life questionnaires were completed during the luteal phase of the menstrual cycle before and after 1, 2, 4, and 6 months of study therapy. Women were contacted by phone during the luteal phase in months 3 and 5 for additional data retrieval.Endpoints of the study included breast examination graded by quadrant for tenderness, size/amount of nodularity, and fibrosis. These data were converted to a standardized score for tenderness (TS) and nodularity (NS). Daily pain assessment from the diary was converted to a standardized pain score (PS). A total CM score represented the sum of these three measures. Changes in quality of life during and after DIAC therapy were also evaluated. The study had the power to detect at least a 30% improvement in the total CM score with beta = 0.80 and alpha = 0.05.Results: Twenty-six sites in 16 states within the United States randomized a total of 385 women with CM. The mean age of women enrolled was 42 years (range 21-73). Over two-thirds of the women had completed study drug intervention as of September 1997. All study drug therapy was to be completed by December 1997 with unblinding in January 1998. No serious or life-threatening side effects had been observed in the trial as of September 1997.Conclusions: DIAC is a promising new therapeutic for CM. The unblinded data from the completed trial assessing safety, efficacy, and quality of life will be presented.