Primary and salvage therapy with LH-RH analogues in ovarian cancer.
Primary and salvage therapy with LH-RH analogues in ovarian cancer.
复制标题
LH-RH 类似物在卵巢癌中的主要治疗和挽救治疗。
DOI：
--
复制
发表时间：
2000
期刊：
影响因子：
--
通讯作者：
K. Schulz
中科院分区：
文献类型：
--
作者：
G. Emons;K. Schulz
现代手术和化疗方案治疗卵巢癌的疗效仍不令人满意。尽管新的细胞毒性药物的可用性，大多数卵巢癌患者将最终死于化疗耐药疾病。常规剂量的LH-RH激动剂已被证明在约9%的难治性卵巢癌患者中诱导客观反应，并在26%的这些女性中诱导疾病稳定。由于LH-RH激动剂的毒性低或没有毒性，并且由于它们的疗效并不明显劣于实验性化疗，因此它们在挽救情况下具有重要的适应症。目前正在铂类/紫杉醇难治性患者中进行一项试验，比较LH-RH激动剂亮丙瑞林和细胞毒性药物treosulfane对生存率和生活质量的影响。在标准一线手术和化疗中加入常规剂量的LH-RH激动剂并不能改善无复发生存率和总生存率。多年来，人们一直认为LH-RH激动剂通过抑制内源性促性腺激素来抑制卵巢癌的增殖，而内源性促性腺激素被认为在这种恶性肿瘤中具有促有丝分裂作用。最近的实验和临床数据使这一假设受到质疑。相反，在过去的几年中出现了大量的实验证据，表明LH-RH激动剂和拮抗剂通过由80%的这些肿瘤表达的LH-RH受体直接抑制卵巢癌的增殖。为了利用LH-RH类似物的这些直接抗增殖作用，需要比目前使用的常规剂量所达到的更高的组织浓度。替代给药途径或更高全身剂量的强效LH-RH拮抗剂，如西曲瑞克，可能会提高这种方法的疗效。解决这个问题的临床试验正在进行中。最后，卵巢癌表达的LH-RH受体可用于使用细胞毒性LH-RH类似物的靶向化疗。这种方法已被证明是有效的实验模型，并可能在不久的将来在临床试验中进行测试。
The efficacy of modern surgical and chemotherapeutic options for the treatment of ovarian cancer is still unsatisfactory. In spite of the availability of new cytotoxic agents, the majority of ovarian cancer patients will finally die of chemoresistant disease. LH-RH agonists in conventional doses have been shown to induce objective responses in approximately 9% of patients with refractory ovarian cancer and disease stabilization in 26% of these women. As toxicity of LH-RH agonists is low or absent, and since their efficacy is not strikingly inferior to that of experimental chemotherapy, they have a vital indication in the salvage situation. A trial is presently being performed among platinum/taxol-refractory patients, comparing the impact of the LH-RH agonist leuprorelin and that of the cytotoxic agent treosulfane on survival and quality of life. The addition of LH-RH agonists in conventional doses to standard first-line surgical and chemotherapy does not improve relapse-free and overall survival. For many years it has been suggested that LH-RH agonists inhibit proliferation of ovarian cancer by suppressing endogenous gonadotropins, which were considered to be mitogenic in this malignancy. Recent experimental and clinical data have made this hypothesis questionable. In contrast, a large body of experimental evidence has emerged during the past few years indicating that LH-RH agonists and antagonists directly inhibit proliferation of ovarian cancer through LH-RH receptors expressed by 80% of these tumors. To exploit these direct antiproliferative effects of LH-RH analogues, higher tissue concentrations are necessary than those achieved with the conventional doses used today. Alternative routes of administration or higher systemic doses of potent LH-RH antagonists, such as Cetrorelix, might improve the efficacy of this approach. Clinical trials addressing this issue are under way. Finally, the LH-RH receptors expressed by ovarian cancers could be employed for targeted chemotherapy using cytotoxic LH-RH analogues. This approach has been shown to be effective in experimental models and might be tested in clinical trials in the near future.