Binaschi Monica, Simonelli Cecilia, Goso Cristina, Bigioni Mario, Maggi Carlo Alberto
Department of Pharmacology, Menarini Ricerche, Pomezia, Rome;
Exp Ther Med. 2011 Mar;2(2):173-180. doi: 10.3892/etm.2011.192. Epub 2011 Jan 14.
Ovarian cancer has the highest mortality rate among gynaecological tumours despite the fact that the majority of patients with advanced disease achieve complete remission after first-line surgery and chemotherapy. Unfortunately, disease recurrence occurs in the majority of patients and second-line treatments are not curative. Clearly, the persistence of dormant and drug-resistant cells after front-line treatments results in the inability to cure the disease. The identification of cancer-initiating cells or cancer stem cells as key players in the development of recurrence has opened up a novel field of research aimed at identifying additional innovative therapeutic approaches. Strategies of maintenance therapy to extend the survival of patients have been studied, but to date no overall survival benefit has been detected. Currently, numerous clinical trials have just been completed or are ongoing involving patients achieving a complete clinical response after first-line chemotherapy in order to evaluate the efficacy of different therapeutic approaches in terms of disease-free survival and overall survival. At the 2010 ASCO meeting, the first positive results of a phase III clinical trial in this setting were presented: bevacizumab (15 mg/kg i.v. every 21 days) added to first-line chemotherapy and continued for an additional 15 cycles was found to prolong progression-free survival of 3.8 months in comparison to 6 cycles of chemotherapy alone or only 6 cycles of chemotherapy plus bevacizumab. In addition, positive results were announced for a second phase III trial testing bevacizumab in the same setting, but at half dose. The final assessment of the overall clinical benefit and the approval of bevacizumab in maintenance therapy by regulatory agencies is expected to be positive, as are the final results of abagovomab phase III trial MIMOSA, another antibody-based therapy tested as a maintenance treatment for advanced ovarian cancer patients. Encouraging preliminary results confirming the safety profile and the immunogenic activity of abagovomab were presented at the last ASCO meeting. The final results are expected to be released in the first half of 2011.
尽管大多数晚期卵巢癌患者在一线手术和化疗后可实现完全缓解，但卵巢癌仍是妇科肿瘤中死亡率最高的疾病。不幸的是，大多数患者会出现疾病复发，二线治疗无法治愈疾病。显然，一线治疗后休眠和耐药细胞的持续存在导致无法治愈该疾病。癌症起始细胞或癌症干细胞被确定为复发发展的关键因素，这开辟了一个新的研究领域，旨在确定更多创新的治疗方法。已经研究了维持治疗策略以延长患者生存期，但迄今为止尚未检测到总体生存获益。目前，许多临床试验刚刚完成或正在进行，涉及在一线化疗后实现完全临床缓解的患者，以评估不同治疗方法在无病生存期和总体生存期方面的疗效。在2010年美国临床肿瘤学会会议上，公布了该情况下一项III期临床试验的首个阳性结果：与单独6周期化疗或仅6周期化疗加贝伐单抗相比，在一线化疗中添加贝伐单抗（每21天静脉注射15mg/kg）并持续额外15周期可使无进展生存期延长3.8个月。此外，在相同情况下以半剂量测试贝伐单抗的第二项III期试验也公布了阳性结果。预计监管机构对贝伐单抗维持治疗的总体临床获益的最终评估及批准将是积极的，阿巴伏单抗III期试验MIMOSA的最终结果也将如此，MIMOSA是另一种基于抗体的疗法，作为晚期卵巢癌患者的维持治疗进行测试。在上次美国临床肿瘤学会会议上公布了令人鼓舞的初步结果，证实了阿巴伏单抗的安全性和免疫原活性。预计最终结果将于2011年上半年公布。
