Cohn David E, Sill Michael W, Walker Joan L, O'Malley David, Nagel Christa I, Rutledge Teresa L, Bradley William, Richardson Debra L, Moxley Katherine M, Aghajanian Carol
Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Ohio State University College of Medicine, Columbus, OH, United States.
NRG Oncology/Gynecologic Oncology Group, Statistics & Data Management, Roswell Park Cancer Institute, Buffalo, NY, United States.
Gynecol Oncol. 2017 Sep;146(3):477-483. doi: 10.1016/j.ygyno.2017.07.135. Epub 2017 Jul 27.
To assess whether the addition of oncolytic reovirus (Reolysin®) to weekly paclitaxel prolonged progression-free survival (PFS) in the treatment of women with recurrent or persistent ovarian, tubal or primary peritoneal cancer.
Patients with recurrent or persistent epithelial ovarian, tubal, or peritoneal carcinoma, measurable or detectable disease, and three or fewer prior regimens were randomly assigned to paclitaxel (80mg/m intravenously days 1, 8, and 15 every 4weeks) or the combination of paclitaxel (80mg/m intravenously days 1, 8, and 15) plus reovirus 3×10TCID/day intravenously on days 1-5, both every 4weeks until disease progression or toxicity. The primary end point was PFS. The study was designed with 80% power for a one-sided alternative at a 10% level of significance to detect a reduction in the hazard by 37.5%.
The study accrued 108 patients, 100 of whom were evaluable for toxicity. Median PFS was 4.3months for paclitaxel and 4.4months for paclitaxel plus reovirus (hazard ratio, 1.11; 90% two-sided CI, 0.78 to 1.59; one-sided P=0.687). The proportion responding (overall response rate) to paclitaxel was 20% among 45 patients with measurable disease receiving paclitaxel alone, and 17.4% among the 46 patients treated with the combination. The asymptotic relative probability of responding was 0.87 (90% CI, 0.42 to 1.79). Severe adverse events were more common in the combination regimen than in paclitaxel arm for severe neutropenia (grade≥4, 12% versus 0%), and severe respiratory adverse events (grade≥3, 25% versus 2%). No deaths were considered treatment related.
The addition of reovirus to weekly paclitaxel in the treatment of women with recurrent or persistent ovarian, tubal or peritoneal cancer did not sufficiently reduce the hazard of progression or death to warrant further investigation.
评估溶瘤呼肠孤病毒（Reolysin®）联合每周一次的紫杉醇治疗复发性或持续性卵巢、输卵管或原发性腹膜癌女性患者时，是否能延长无进展生存期（PFS）。
复发性或持续性上皮性卵巢癌、输卵管癌或腹膜癌患者，疾病可测量或可检测，且既往接受过的治疗方案不超过三种，被随机分配至紫杉醇组（每4周第1、8和15天静脉注射80mg/m）或紫杉醇联合组（第1、8和15天静脉注射80mg/m的紫杉醇，第1 - 5天每天静脉注射3×10TCID的呼肠孤病毒），均每4周进行一次，直至疾病进展或出现毒性反应。主要终点为PFS。该研究设计的检验效能为80%，用于在10%的显著性水平下进行单侧检验，以检测风险降低37.5%。
该研究共纳入108例患者，其中100例可评估毒性。紫杉醇组的中位PFS为4.3个月，紫杉醇联合呼肠孤病毒组为4.4个月（风险比，1.11；90%双侧置信区间，0.78至1.59；单侧P = 0.687）。在仅接受紫杉醇治疗的45例可测量疾病患者中，对紫杉醇有反应的比例（总缓解率）为20%，在联合治疗的46例患者中为17.4%。有反应的渐近相对概率为0.87（90%置信区间，0.42至1.79）。联合治疗方案中严重不良事件比紫杉醇组更常见，严重中性粒细胞减少（≥4级，12%对0%）和严重呼吸不良事件（≥3级，25%对2%）。未发现与治疗相关的死亡病例。
在复发性或持续性卵巢、输卵管或腹膜癌女性患者的治疗中，呼肠孤病毒联合每周一次的紫杉醇治疗未能充分降低疾病进展或死亡风险，因此不值得进一步研究。
