A pilot study of cabergoline for the treatment of metastatic breast cancer.

PURPOSE: The prolactin (PRL) receptor is over-expressed in breast cancer, and pre-clinical data indicate that it contributes to breast oncogenesis. Cabergoline is a potent dopamine receptor agonist of D2 receptors and has a direct inhibitory effect on pituitary PRL secretion. METHODS: A phase II study of cabergoline in patients with metastatic breast cancer was conducted. The primary end point of the study was to determine the clinical benefit rate (CBR) at 2 months. Eligible patients had tumors of any receptor status with no limit of prior lines of therapy. Measurable and unmeasurable diseases were allowed. Cabergoline 1 mg orally, twice weekly (1 cycle = 4 weeks) was given until disease progression or unacceptable toxicity. PRL receptor immunohistochemical staining was performed on available baseline tumor tissue; serial serum PRL levels were assessed. RESULTS: Twenty women were enrolled; 18 were evaluable for CBR. Tumor receptor status was distributed as follows: HR-any/HER2+ 2(10%), HR+/HER2- 18 (90%). The CBR was 33% (6/18), median progression free survival was 1.8 months, and median overall survival was 10.4 months. Two patients experienced disease control for over 12 months. Most common treatment-related adverse events were nausea (30%), fatigue (25%), and elevation in alkaline phosphatase (15%). Nine patients had baseline tissue for analysis; there was no association between baseline tumor PRL receptor expression and clinical benefit (p = 0.24). Change in serum PRL level and response were not correlated after 2 months of treatment (p = 0.64). CONCLUSION: Cabergoline was well tolerated, and while the ORR was low, a small subset of patients experienced extended disease control.

Ontogeny of ultradian and nocturnal activity rhythms in the isolated albino rat.

The activity of isolated rats from 6 to 25 days of age was analyzed at 10-min intervals. Ultradian peak activity rhythms, with a rough 1-2-hr periodicity, developed between 9 and 12 days of age, and reached an extreme at 15 days. Ultradian periods of attenuated activity were however detectable even in 6-day-olds. Isolated rats at 15 days of age displayed greatly accentuated profiles characterized not only by heightened activity levels, but by an extreme cyclicity. These subjects spent most of their time oscillating between periods of marked activity and marked inactivity. Both the average and total duration of these extreme periods were greater in 15-day-olds than any of the other ages. Free-running nocturnal activity rhythms were also observed to develop in isolated rats tested in continuous darkness by the 15th day.