Lissoni P, Vaghi M, Villa S, Bodraska A, Cerizza L, Tancini G, Gardani G S
Division of Radiation, Oncology, San Gerardo Hospital, 20052 Monza, Milan, Italy.
Anticancer Res. 2003 Jan-Feb;23(1B):733-6.
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.
尽管催乳素（PRL）对乳腺癌细胞生长的刺激作用已得到充分证实，且雌激素非依赖性乳腺肿瘤可能存在PRL依赖性，但抗催乳素药物在人类乳腺癌治疗中的作用仍有待研究和明确。先前的初步研究已经表明，同时给予抗催乳素药物可能会增强乳腺癌化疗的疗效，而它们对内分泌治疗疗效的影响仍不清楚。目前，乳腺癌的经典内分泌治疗包括抗雌激素药物加促性腺激素释放激素（LHRH）类似物。同时给予抗催乳素药物不仅可以通过阻断雌激素的作用，还可以通过阻断乳腺癌的另一种生长因子（如PRL）的作用来提高治疗效果。本II期研究旨在评估一种针对乳腺癌的多神经内分泌治疗方法的疗效和耐受性，该方法包括LHRH类似物、抗雌激素他莫昔芬和长效抗催乳素药物卡麦角林。该研究纳入了14例连续的转移性乳腺癌女性患者，她们均接受过标准抗癌治疗且病情严重，没有其他可用的常规治疗方法。LHRH类似物曲普瑞林每28天肌肉注射一次，剂量为3.75mg；他莫昔芬口服，剂量为每天20mg；卡麦角林口服，剂量为每周0.5mg。临床反应包括14例患者中有4例（29%）出现部分缓解（PR），其中1例患者之前单独使用曲普瑞林加他莫昔芬治疗时病情进展。另外5例患者病情稳定（SD），其余5例患者病情进展（PD）。治疗第一个月内，患者血清PRL平均水平显著下降，PR或SD患者的下降明显比PD患者更显著。所有患者对治疗耐受性良好，特别是未发生与卡麦角林相关的毒性反应。这项初步研究表明，长效抗催乳素药物卡麦角林的联合使用可能会进一步提高抗雌激素药物加LHRH类似物的经典内分泌疗法对晚期乳腺癌的疗效。
