Anticancer Res. 2004 Nov-Dec;24(6):4223-6.
Enhancement of the efficacy of weekly low-dose taxotere by the long acting anti-prolactinemic drug cabergoline in pretreated metastatic breast cancer.
Frontini L,
Lissoni P,
Vaghi M,
Perego MS,
Pescia S,
Ardizzoia A,
Gardani G.
Division of Radiation Oncology, San Gerardo Hospital, Monza, Milan, Italy.
In view of its potential action as a growth factor, the
evidence of abnormally high blood levels of prolactin (PRL) is associated with a poor prognosis in metastatic breast cancer. Moreover, metastatic breast cancer-related
hyperprolactinemia has proven to counteract the efficacy of cancer chemotherapy. The negative influence of high blood levels of PRL on the efficacy of chemotherapy in metastatic breast cancer has been confirmed by previous preliminary studies, showing that the
concomitant administration of the anti-prolactinemic dopaminergic agent bromocriptine may enhance the therapeutic effect of chemotherapy. However, the clinical use of bromocriptine is limited by its short duration and gastrointestinal toxicity. Therefore, new anti-prolactinemic drugs, characterized by less toxicity and a longer duration of activity, such as
Cabergoline (CBG), could be more appropriated to control PRL secretion in breast cancer. On this basis,
a study was planned to evaluate the efficacy and tolerability of a concomitant administration of CBG with weekly low-dose Taxotere (TXT) in pretreated metastatic breast cancer under chemotherapy. The study group comprised 70 metastatic breast cancer patients (females), pretreated with at least one previous chemotherapeutic line containing anthracyclines, who were randomized to be treated with TXT alone or TXT plus CBG.
TXT 25 mg/m2 was given i.v. at weekly intervals for at least 9 consecutive cycles. CBG was given orally at 0.5 mg once per week. Abnormally high pre-treatment levels of PRL were seen in 24/70 (34%) patients, 11 of whom were treated with TXT plus CBG, whereas the other 13 received TXT alone. CBG induced a complete normalization of the PRL levels in all patients within the first two weeks of therapy, whereas no normalization of PRL occurred spontaneously in patients treated with chemotherapy alone. The
objective tumor regression rate was significantly higher in patients concomitantly treated with CBG than in those who received chemotherapy alone(31/34 vs 13/36, p < 0.05), and this difference was particularly evident in patients with high PRL levels prior to therapy (6/11 vs 2/13).
No CBG-related toxicity occurred. On the contrary, chemotherapy-induced asthenia was significantly lower in patients concomitantly treated with CBG (5/34 vs 11/36, p < 0.05). This study shows that the chemoneuroendocrine therapy of weekly low-dose TXT plus the anti-prolactinemic drug CBG is
a new, effective and well-tolerated therapy for metastatic breast cancer. It may also be recommended in heavily pretreated patients or in those with poor clinical status.
PMID: 15736476 [PubMed - indexed for MEDLINE]
J Biol Regul Homeost Agents. 2004 Jul-Dec;18(3-4):291-4.
Biological response modifiers of cancer-related neuroendocrine disorders: efficacy of the long-term dopaminergic agonist cabergoline in the treatment of breast cancer-induced hyperprolactinemia.
Lissoni P,
Vaghi M,
Pescia S,
Rovelli F,
Ardizzola A,
Valtulina F,
Malugani F,
Gardani G,
Tancini G.
S Gerardo Hospital, Monza, Milano, Italy.
The
evaluation of the biological status of cancer patients should not be limited only to investigation of immune reactivity, but should also include analysis of the endocrine condition, namely concerning those hormones which have appeared to be tumor growth factors, such as prolactin (PRL) for breast and prostate carcinomas. This statement is justified by the fact that the evidence of abnormally high serum concentrations of PRL has been proven to be associated with poor prognosis in breast and prostate cancer patients. Moreover, since hyperprolactinemia negatively influences the efficacy of anticancer therapies in breast cancer, it could be fundamental to achieve a normalization of PRL levels by long-acting dopaminergic agents, such as cabergoline. On this basis, a study was planned to evaluate the effect of cabergoline on PRL levels in hyperprolactinemic metastatic breast cancer subjects. The study included 20 hyperprolactinemic metastatic breast cancer subjects, who were randomized to receive no therapy or cabergoline at 0.5 mg/week orally for 4 consecutive weeks. Cabergoline therapy induced a normalization in all patients, whereas no spontaneous normalization of PRL levels occured in the control group. These results show that
a weekly oral administration of the long-acting dopaminergic agent cabergoline is a well tolerated and effective treatment of metastatic breast cancer-related hyperprolactinemia. The possible prognostic impact of PRL normalization needs to be established by successive studies.
PMID: 15786695 [PubMed - indexed for MEDLINE]
Anticancer Res. 2003 Jan-Feb;23(1B):733-6.
Antiprolactinemic approach in the treatment of metastatic breast cancer: a phase II study of polyneuroendocrine therapy with LHRH-analogue, tamoxifen and the long-acting antiprolactinemic drug cabergoline.
Lissoni P,
Vaghi M,
Villa S,
Bodraska A,
Cerizza L,
Tancini G,
Gardani GS.
Division of Radiation, Oncology, San Gerardo Hospital, 20052 Monza, Milan, Italy.
Despite the well-demonstrated stimulatory role of prolactin (PRL) on breast cancer cell growth and the possible existence of a PRL-dependency in estrogen-independent mammary tumors, the therapeutic role of the antiprolactinemic drugs in the treatment of human breast cancer has still to be investigated and defined.
Previous preliminary studies have already shown that the concomitant administration of antiprolactinemic agents may enhance the efficacy of cancer chemotherapy for breast carcinoma, whereas their impact on the efficacy of the endocrine therapy is still unknown.
At present, the classic endocrine therapy for breast cancer consists of anti-estrogens plus LHRH-analogue. The concomitant administration of antiprolactinemic drugs could enhance the efficacy of treatment by blocking not only the action of estrogens, but also that of another growth factor for breast cancer, such as PRL. The present phase II study was performed to evaluate the efficacy and tolerability of a polyneuroendocrine approach for breast cancer, consisting of LHRH-analogue plus the anti-estrogen tamoxifen plus a long-acting antiprolactinemic agent, cabergoline. The study included 14 consecutive metastatic breast cancer women, heavily pretreated with the standard anticancer therapies and for whom no other conventional treatment was available. The LHRH-analogue, triptorelin, was given intramuscularly at a dose of 3.75 mg every 28 days, tamoxifen was given orally at 20 mg/day and cabergoline was given orally at 0.5 mg once/week. The clinical response consisted of partial response (PR) in 4 out of 14 (29%) patients, including one who had progressed on a previous treatment with triptorelin plus tamoxifen alone. A stable disease (SD) was achieved in another 5 patients, whereas the other 5 patients had a progressive disease (PD).
Mean serum levels of PRL significantly decreased on treatment within the first month of therapy, and its decline was significantly more evident in patients with PR or SD than in those with PD. The treatment was well-tolerated in all patients, and in particular no cabergoline-related toxicity occurred. This preliminary study would suggest that the association of the long-acting antiprolactinemic drug
cabergoline may further enhance the efficacy of the classical endocrine therapy for advanced breast cancer with anti-estrogens plus LHRH-analogues.
PMID: 12680176 [PubMed - indexed for MEDLINE]
Neoplasma. 2010;57(1):74-8.
Relationship between plasma progesterone, estradiol and prolactin concentrations and breast cancer in pre and postmenopausal women.
Raheem SN,
Atoum M,
Al-Hourani H,
Rasheed M,
Nimer N,
Almuhrib T.
Hormones such as estrogen, progesterone and prolactin are implicated in anumber of ways as possible causes of breast cancer. Throughout women life cycle, breast development and function depend on complex critical interplay of these hormones. The acknowledged gaps in our understanding concerning progesterone, estrogen and prolactin hormones involvement in human breast cancer has exposed the need to conduct this study for better understanding of the role played by these hormones in breast cancer during pre and post menopause status in order to influence prevention and treatment of breast cancer. Ninety women were enrolled, (80%) of them were breast cancer patients and the other (20%) were breast benign lesion patients. At attending King Hussein Medical Center, blood samples were collected and analyzed for plasma estradiol, prolactin and progesterone. Of the 72 breast cancer patients (66.6% and 33.4%), and of the 18 breast benign patients (27.8% and 72.2%) were in menopause and premenopausal, respectively. Of the breast cancer and benign patients groups, 55.6% of each had an association with either high plasma estradiol, prolactin or progesterone concentrations. Of the breast cancer patients that had association with high plasma hormonal concentrations, 47.5% had high plasma estradiol concentrations (155.0+/-36 pg/ml) and 89.5% of these were in menopause. Of the breast benign patients, 60% had high plasma prolactin concentrations (55.2+/-10.6 ng/ml). Menopausal breast cancer is associated with high plasma estradiol concentrations, while premenopausal breast benign were associated high plasma prolactin concentrations which indicate that high plasma estradiol in menopause is arisk factor for breast cancer development while high prolactin in premenopausal is arisk factor for breast benign. Therefore, breast cancer and benign are highly hormonal dependent. Keywords: breast cancer, premenopausal and postmenopausal, plasma hormones.
PMID: 19895176 [PubMed - in process]
Intern Med J. 2009 Apr;39(4):266-7.
Low-dose cabergoline causing valvular heart disease in a patient treated for prolactinoma.
Cawood TJ,
Bridgman P,
Hunter L,
Cole D.
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