Onda Takashi, Satoh Toyomi, Saito Toshiaki, Kasamatsu Takahiro, Nakanishi Toru, Nakamura Kenichi, Wakabayashi Masashi, Takehara Kazuhiro, Saito Motoaki, Ushijima Kimio, Kobayashi Hiroaki, Kawana Kei, Yokota Harushige, Takano Masashi, Takeshima Nobuhiro, Watanabe Yoh, Yaegashi Nobuo, Konishi Ikuo, Kamura Toshiharu, Yoshikawa Hiroyuki
Department of Gynecology, Kitasato University School of Medicine, Japan.
Department of Obstetrics and Gynecology, Faculty of Medicine, University of Tsukuba, Japan.
Eur J Cancer. 2016 Sep;64:22-31. doi: 10.1016/j.ejca.2016.05.017. Epub 2016 Jun 17.
We conducted a phase III, non-inferiority trial comparing upfront primary debulking surgery (PDS) and interval debulking surgery (IDS) following neoadjuvant chemotherapy (NAC) for stage III/IV ovarian, tubal, and peritoneal cancers (JCOG0602). Two earlier studies, EORTC55971 and CHORUS, demonstrated non-inferior survival of patients treated with NAC. However, they could not evaluate true treatment invasiveness because of adding diagnostic laparotomy or laparoscopy before treatment in over 30% of both arms of EORTC55971 and in 16% of NAC arm of CHORUS.
Patients were randomised into the standard arm (PDS followed by eight cycles of paclitaxel and carboplatin [TC]) and NAC arm (four cycles of TC, IDS, and four cycles of TC). In the standard arm, IDS was optional for patients who had undergone suboptimal or incomplete PDS. Treatment invasiveness was compared between arms (UMIN000000523).
Between November 2006 and October 2011, 301 patients were randomised. In the standard arm, 147/149 underwent PDS and 49 underwent IDS. In the NAC arm, 130/152 underwent IDS. The NAC arm required fewer surgeries (mean 0.86 versus 1.32, p < 0.001) and shorter total operation time (median 273 min versus 341 min, p < 0.001) than the standard arm and required a lower frequency of abdominal organ resection (23.7% versus 37.6%, p = 0.012) or distant metastases resection (3.9% versus 10.7%, p = 0.027). In the NAC arm IDS, blood/ascites loss was smaller (median 787 ml versus 3235 ml, p < 0.001) and albumin transfusion and G3/4 adverse events after surgery in total were less frequent (26.2% versus 58.5%, p < 0.001; 4.6% versus 15.0%, p = 0.005, respectively).
Our findings demonstrated that NAC treatment is less invasive than standard treatment. NAC treatment may become the new standard treatment for advanced ovarian cancer when non-inferior survival is confirmed in the planned primary analysis in 2017.
我们开展了一项III期非劣效性试验（JCOG0602），比较新辅助化疗（NAC）后一线初次肿瘤细胞减灭术（PDS）和中间性肿瘤细胞减灭术（IDS）用于III/IV期卵巢癌、输卵管癌和腹膜癌的疗效。两项早期研究，即欧洲癌症研究与治疗组织（EORTC）55971试验和CHORUS试验，已证实NAC治疗的患者生存率非劣效。然而，由于EORTC55971试验两组中超过30%的患者以及CHORUS试验NAC组中16%的患者在治疗前增加了诊断性剖腹术或腹腔镜检查，所以这两项研究无法评估真正的治疗侵袭性。
患者被随机分为标准组（PDS后接受8个周期的紫杉醇和卡铂[TC]）和NAC组（4个周期的TC、IDS及4个周期的TC）。在标准组中，对于接受次优或不完全PDS的患者，IDS为可选方案。比较两组之间的治疗侵袭性（UMIN000000523）。
2006年11月至2011年10月期间，301例患者被随机分组。在标准组中，147/149例患者接受了PDS，49例接受了IDS。在NAC组中，130/152例患者接受了IDS。与标准组相比，NAC组所需手术更少（平均0.86次对1.32次，p<0.001），总手术时间更短（中位数273分钟对341分钟，p<0.001），腹部器官切除频率更低（23.7%对37.6%，p=0.012）或远处转移灶切除频率更低（3.9%对10.7%，p=0.027）。在NAC组的IDS中，术中失血/腹水丢失更少（中位数787毫升对3235毫升，p<0.001），术后白蛋白输注及总体G3/4级不良事件发生率更低（分别为26.2%对58.5%，p<0.001；4.6%对15.0%，p=0.005）。
我们的研究结果表明，NAC治疗的侵袭性低于标准治疗。如果在2017年计划进行的初步分析中证实NAC治疗的生存率非劣效，那么NAC治疗可能会成为晚期卵巢癌的新的标准治疗方法。
