Enhancement of the efficacy of weekly low-dose taxotere by the long acting anti-prolactinemic drug cabergoline in pretreated metastatic breast cancer.
Enhancement of the efficacy of weekly low-dose taxotere by the long acting anti-prolactinemic drug cabergoline in pretreated metastatic breast cancer.
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发表时间：
2004-11
影响因子：
2
通讯作者：
L. Frontini;P. Lissoni;M. Vaghi;M. Perego;S. Pescia;A. Ardizzoia;G. Gardani
中科院分区：
文献类型：
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作者：
L. Frontini;P. Lissoni;M. Vaghi;M. Perego;S. Pescia;A. Ardizzoia;G. Gardani
鉴于其作为生长因子的潜在作用，血中异常高水平的催乳素（PRL）与转移性乳腺癌的预后不良有关。此外，转移性乳腺癌相关的高泌乳素血症已被证明会抵消癌症化疗的疗效。先前的初步研究已经证实了高血PRL水平对转移性乳腺癌化疗疗效的负面影响，表明同时给予抗催乳素血症多巴胺能药物溴隐亭可能会增强化疗的疗效。然而，溴隐亭的临床使用受到其持续时间短和胃肠道毒性的限制。因此，新的抗催乳素血症药物，其特点是毒性较小，活性持续时间较长，如卡麦角林（CBG），可能更适合于控制乳腺癌的PRL分泌。在此基础上，计划进行一项研究，以评价CBG与每周一次低剂量泰索帝（TXT）合并给药在接受化疗的预治疗转移性乳腺癌中的疗效和耐受性。研究组包括70例转移性乳腺癌患者（女性），接受过至少一种含蒽环类药物的既往化疗方案预治疗，随机接受单用TXT或TXT + CBG治疗。TXT 25 mg/m2静脉给药，每周一次，至少连续9个周期。口服CBG 0.5 mg，每周一次。在24/70（34%）例患者中观察到治疗前PRL水平异常高，其中11例接受TXT加CBG治疗，而其他13例仅接受TXT治疗。CBG在治疗的前两周内诱导所有患者的PRL水平完全正常化，而在仅接受化疗的患者中没有自发发生PRL正常化。CBG联合治疗患者的客观肿瘤消退率显著高于单纯化疗患者（31/34 vs 13/36，p < 0.05），这种差异在治疗前PRL水平较高的患者中尤其明显（6/11 vs 2/13）。未发生CBG相关毒性。相反，化疗引起的虚弱在伴随CBG治疗的患者中显著降低（5/34 vs 11/36，p < 0.05）。本研究表明，每周低剂量TXT联合抗催乳素药CBG的化学神经内分泌疗法是治疗转移性乳腺癌的一种新的、有效的和耐受性良好的疗法。它也可能被推荐用于重度预治疗患者或临床状态不佳的患者。
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.