Gadducci Angiolo, Cosio Stefania, Genazzani Andrea Riccardo
Department of Procreative Medicine, Division of Gynecology and Obstetrics, University of Pisa, Via Roma 56, Pisa 56127, Italy.
Crit Rev Oncol Hematol. 2006 Jun;58(3):242-56. doi: 10.1016/j.critrevonc.2005.11.002. Epub 2006 Jan 24.
Hormonal therapy and chemotherapy play a major role in the management of advanced or recurrent endometrial cancer. Progesterone therapy obtains overall response rates ranging from 11% to 25% in patients with endometrioid-type tumours, and oral medroxyprogesterone acetate 200mg daily appears to be a reasonable therapeutic option for those lesions that are well differentiated and/or have a high progesterone receptor (PgR) content. However, the activity of progestins is often compromised by the down-regulation of PgR within the target tissues, and therefore therapeutic strategies designed to enhance PgR expression are warranted. Little data are currently available about the new aromatase inhibitors and selective estrogen receptor modulators. As for chemotherapy, the combination of doxorubicin [DOX]+cisplatin [CDDP] achieves overall response rates ranging from 34% to 60%, and the addition of paclitaxel (TAX) seems to improve response rates, progression-free survival and overall survival, but to worsen toxicity profile. A phase III study is currently comparing TAX+DOX+CDDP versus the less toxic combination of TAX+carboplatin. Chemotherapy is active against both endometrioid-type carcinoma and uterine serous papillary carcinoma. However, this latter endometrial malignancy is less chemosensitive than the histologically similar high-grade serous ovarian carcinoma. Interesting fields of research are represented by investigational agents directed against specific intracellular signal transduction pathways involved in the proliferation, invasiveness and metastatic spread of endometrial cancer. Mammalian target of the rapamycin (mTOR) inhibitors, epidermal growth factor receptor inhibitors (gefitinib, erlotinib, lapatinib, the monoclonal antibody cetuximab), imatinib, the monoclonal antibody trastuzumab, and the Clostridium perfrigens enterotoxin are currently under evaluation as molecularly targeted therapies for endometrial cancer. Further investigations addressed to better understand the signal transduction pathways that are disregulated in endometrial carcinogenesis could identify novel biological targets suitable for tailored therapies.
激素疗法和化疗在晚期或复发性子宫内膜癌的治疗中发挥着重要作用。孕激素疗法使子宫内膜样肿瘤患者的总体缓解率在11%至25%之间，对于高分化和/或孕激素受体（PgR）含量高的病变，每日口服200mg醋酸甲羟孕酮似乎是一种合理的治疗选择。然而，孕激素的活性常常因靶组织内PgR的下调而受到影响，因此有必要设计增强PgR表达的治疗策略。目前关于新型芳香化酶抑制剂和选择性雌激素受体调节剂的数据很少。至于化疗，阿霉素[DOX]+顺铂[CDDP]联合使用的总体缓解率在34%至60%之间，添加紫杉醇（TAX）似乎可提高缓解率、无进展生存期和总生存期，但会使毒性增加。一项III期研究正在比较TAX+DOX+CDDP与毒性较小的TAX+卡铂联合方案。化疗对子宫内膜样癌和子宫浆液性乳头状癌均有活性。然而，后一种子宫内膜恶性肿瘤的化疗敏感性低于组织学上相似的高级别浆液性卵巢癌。针对参与子宫内膜癌增殖、侵袭和转移扩散的特定细胞内信号转导途径的研究药物代表了有趣的研究领域。雷帕霉素的哺乳动物靶点（mTOR）抑制剂、表皮生长因子受体抑制剂（吉非替尼、厄洛替尼、拉帕替尼、单克隆抗体西妥昔单抗）、伊马替尼、单克隆抗体曲妥珠单抗和产气荚膜梭菌肠毒素目前正在作为子宫内膜癌的分子靶向疗法进行评估。进一步的研究旨在更好地了解在子宫内膜癌发生过程中失调的信号转导途径，这可能会确定适合个体化治疗的新生物靶点。
