D'Antonio Chiara, Passaro Antonio, Gori Bruno, Del Signore Ester, Migliorino Maria Rita, Ricciardi Serena, Fulvi Alberto, de Marinis Filippo
1st Oncological Pulmonary Unit/Department of Medical and Surgical Sciences and Translational Medicine, 'Sapienza' University of Rome, Sant'Andrea Hospital San Camillo, High Specialization Hospital/University of Rome, Sant'Andrea Hospital, Cir. ne Gianicolense 87, 00151, Rome, Italy.
Division of Thoracic Oncology, European Institute of Oncology, Milan, Italy.
Ther Adv Med Oncol. 2014 May;6(3):101-14. doi: 10.1177/1758834014521110.
Bone and brain metastases are a very common secondary localization of disease in patients with lung cancer. The prognosis of these patients is still poor with a median survival of less than 1 year. Current therapeutic approaches include palliative radiotherapy and systemic therapy with chemotherapy and targeted agents. For bone metastasis, zoledronic acid is the most commonly used bisphosphonate to prevent, reduce the incidence and delay the onset of skeletal-related events (SREs). Recently, denosumab, a fully human monoclonal antibody directed against the receptor activator of nuclear factor κB (RANK) ligand inhibiting the maturation of pre-osteoclasts into osteoclasts, showed increased time to SREs and overall survival compared with zoledronic acid. The treatment of brain metastasis is still controversial. Available standard therapeutic options, such as whole brain radiation therapy and systemic chemotherapy, provide a slight improvement in local control, overall survival and symptom relief. More recently, novel target agents such as the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) erlotinib, gefitinib and afatinib have shown activity in patients with brain metastasis. Inter alia, in patients harboring EGFR mutations, the administration of EGFR TKIs is followed by a response rate of 70-80%, and a longer progression-free and overall survival than those obtained with standard chemotherapeutic regimens. This review is focused on the evidence for therapeutic strategies in bone and brain metastases due to lung cancer.
骨转移和脑转移是肺癌患者非常常见的疾病继发部位。这些患者的预后仍然很差，中位生存期不到1年。目前的治疗方法包括姑息性放疗以及化疗和靶向药物的全身治疗。对于骨转移，唑来膦酸是最常用的双膦酸盐，用于预防、降低骨相关事件（SREs）的发生率并延迟其发生。最近，地诺单抗是一种完全人源化单克隆抗体，靶向核因子κB受体激活剂（RANK）配体，可抑制破骨细胞前体成熟为破骨细胞，与唑来膦酸相比，其显示出SREs发生时间延长和总生存期延长。脑转移的治疗仍存在争议。现有的标准治疗选择，如全脑放疗和全身化疗，在局部控制、总生存期和症状缓解方面略有改善。最近，新型靶向药物，如表皮生长因子受体（EGFR）酪氨酸激酶抑制剂（TKIs）厄洛替尼、吉非替尼和阿法替尼，已在脑转移患者中显示出活性。特别是，在携带EGFR突变的患者中，给予EGFR TKIs后的缓解率为70-80%，无进展生存期和总生存期比标准化疗方案更长。本综述重点关注肺癌骨转移和脑转移治疗策略的证据。
