ergoline and Neoplasm-Metastasis

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.. 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.. 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).. Cabergoline was well tolerated, and while the ORR was low, a small subset of patients experienced extended disease control.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Agents; Biomarkers; Breast Neoplasms; Cabergoline; Disease Progression; Ergolines; Female; Humans; Middle Aged; Neoplasm Metastasis; Neoplasm Staging; Pilot Projects; Retreatment; Treatment Outcome

The prolactin release inhibiting action of the dopamine receptor agonist metergoline was investigated in 16 patients with metastatic breast cancer associated with hyperprolactinemia. At a daily dose of 12 mg p.o. for 30 days, the drug was highly effective in lowering prolactin levels (day 0: 1076 +/- 171, day 29: 249 +/- 46 mU/l) in these patients. Starting treatment with 4 mg/day, the side effects of the treatment were mild, including dizziness and nausea.

Topics: Breast Neoplasms; Drug Evaluation; Ergolines; Female; Follicle Stimulating Hormone; Humans; Hyperprolactinemia; Luteinizing Hormone; Metergoline; Middle Aged; Neoplasm Metastasis; Prognosis; Prolactin; Receptors, Dopamine; Thyrotropin

A patient with a primary adenohypophyseal neoplasm who had a long course marked by multiple surgical resections, radiation therapy, and high-dose dopamine agonist therapy developed local invasion as well as cranial and extracranial osseous metastatic lesions. The serum prolactin levels were greatly elevated, and immunohistochemical studies demonstrated prolactin in the cytoplasm of primary and metastatic tumor cells. Ultrastructural features of lactotrophic differentiation, including misplaced granule exocytosis, were observed. This is the third reported case of prolactin cell carcinoma that metastasized despite high-dose dopamine agonist therapy. Analysis of the patient's serum prolactin showed no abnormality in the chromatographic profile of biologic activity.

Topics: Biological Assay; Brain Neoplasms; Bromocriptine; Combined Modality Therapy; Ergolines; Female; Histocytochemistry; Hormones; Humans; Microscopy, Electron; Middle Aged; Neoplasm Invasiveness; Neoplasm Metastasis; Pergolide; Pituitary Neoplasms; Prolactin

A brief account of the concept of hormone dependence in breast neoplasia is followed by the presentation of results obtained with an association of medroxyprogesterone acetate (MAP) and 2-bromo-alpha-ergocriptine (CB 154) in 14 women with metastatic cancer of the breast, hormone dependent due to the presence of the cytoplasmic receptor for 17-beta-oestradiol. All patients, in fertile or premenopausal stage, were subjected to prior surgical ovariectomy. MAP was given i.m. at a dose of 1 g/day for 30 days and then 150 mg/day. In the same time 2.5 mg CB 154 were administered every 6 hr per os. Evaluation in accordance with the criteria proposed by the Coop Breast Cancer Group showed that rapid improvement was obtained in all cases, persisting (at the time of writing) for a minimum of 6 months to a maximum of 2 yr of observation. In addition, rapid disappearance of pain was noted, particularly in subjects with secondary bone lesions. Side-effects were in all cases of slight consequence and suspension of the treatment was never necessary. The mechanism of the two drugs and the advantages of their association are discussed.. 14 patients, either of fertile age or perimenopausal and affected with metastatic breast cancer as a consequence of oral contraception, were treated with a combination of medroxyprogesterone acetate and bromocriptine. All patients had previously undergone ovariectomy and, in some cases, mastectomy. Evaluation of results were in accordance with the criteria proposed by the Cooperative Breast Cancer Group. There were no serious side effects and a rapid disappearance of pain; suspension of treatment was never necessary. The good results and the rapid improvement obtained show this treatment to be superior to any experimented up to now by this group of authors.

Topics: Adult; Aged; Breast Neoplasms; Bromocriptine; Drug Evaluation; Drug Therapy, Combination; Ergolines; Female; Humans; Medroxyprogesterone; Middle Aged; Neoplasm Metastasis; Receptors, Estrogen