Cabergoline in the Management of Nonfunctioning Pituitary Adenoma

1. BACKGROUND and study rationale The overall prevalence of pituitary adenoma in the general population ranges from 1 in 865 to 1 in 2688 adults. Of these tumors, between 15% and 54% are nonfunctioning pituitary adenomas (NFPAs). Most NFPAs are macroadenomas with diameter greater than 10 mm. Generally, surgery is recommended as first-line treatment of symptomatic NFPAs. However, medical therapies or radiation therapy or active surveillance may be indicated for some patients.

Cabergoline (Dostinex), a dopamine agonist which has been widely used to treat hyperprolactinemia, prolactinoma for many years. For NFPA, there were studies revealing that dopamine agonists might reduce residual tumor size postoperatively. But those studies were most observational studies and performed retrospectively. There is only one randomized controlled trial assessing the effect of cabergoline on post-operative residual NFPA. The result showed cabergoline was an effective drug for treating residual NFPA, and its use was associated with a high rate of tumor shrinkage. Therefore, nowadays dopamine agonist treatment is usually reserved for the treatment of residual tumor postoperatively. Though, there were reports showing dopamine agonist may reduce the size of NFPAs. Nevertheless, there is no report using dopamine agonist as primary treatment of NFPAs, especially preoperatively.

Furthermore, responsible mechanisms of dopamine agonists in NFPA remain poorly understood. Therefore, randomized controlled trial focusing on the effect of dopamine agonists on NFPA is needed.

Hence, we designed a multicenter, open-label, randomized, controlled parallel study to evaluate the effect of cabergoline on the tumor size among patients diagnosed with NFPA. 2. STUDY OBJECTIVES 2.1 Primary Objective The primary objective is to assess the effect of cabergoline on tumor size by comparing the proportion of tumor shrinkage between cabergoline and control group. The change of tumor size will be measured by the maximal diameter of tumor and estimated volume of the tumor over the 48 week-treatment period.

2.2 Secondary Objectives The secondary objective is to assess the effect of cabergoline via measurement of progression -free survival (PFS) over the 48 week-treatment period. Besides, the largest diameter of tumor and estimated volume of tumor will also be recorded and compared between groups. 3. STUDY DESIGN 3.1 Study Overview This is a multiple center, open-labeled, controlled, randomized, parallel study. 30 of subjects over 18 years old are planned. Subjects must be consenting adult volunteers who were diagnosed with NFPA, whose tumor size are at least 0.5cm in diameter and recent serum prolactin levels are less than 30ng/ml. Besides, subjects used to undergo either brain surgery or radiotherapy, subjects currently receiving any product of dopamine agonist will not be enrolled.