Department of Gynaecology, University of Marburg, Marburg.
Department of Gynaecology and Gynaecological Oncology, HSK Wiesbaden and Kliniken Essen Mitte, Essen.
Ann Oncol. 2012 Sep;23(9):2265-2271. doi: 10.1093/annonc/mds003. Epub 2012 Feb 29.
Recurrent platinum-resistant ovarian cancer usually has a poor outcome with conventional chemotherapeutic therapy and new treatment modalities are warranted. This phase II study was conducted to evaluate sunitinib, an oral antiangiogenic multitargeted tyrosin kinase inhibitor, in this setting.
The primary end point of this randomized phase II trial was the objective response rate according to RECIST criteria and/or Gynecologic Cancer InterGroup CA125 response criteria to sunitinib in patients with recurrent platinum-resistant ovarian cancer who were pretreated with up to three chemotherapies. A selection design was employed to compare two schedules of sunitinib (arm 1: 50 mg sunitinib daily orally for 28 days followed by 14 days off drug; and arm 2: 37.5 mg sunitinib administered daily continuously).
Of 73 patients enrolled, 36 patients were randomly allocated to the noncontinuous treatment arm (arm 1) and 37 patients were randomly allocated to the continuous treatment arm (arm 2). The mean age was 58.8 and 58.5 years, respectively. We observed six responders (complete response + partial response) in arm 1 (16.7%) and 2 responders in arm 2 (5.4%). The median progression-free survival (arm 1: 4.8 [2.9-8.1] months; arm 2: 2.9 [2.9-5.1] months) and the median overall survival (arm 1: 13.6 [7.0-23.2] months; arm 2: 13.7 [8.4-25.6] months) revealed no significant difference. Adverse events included fatigue as well as cardiovascular, gastrointestinal and abdominal symptoms, hematologic and hepatic laboratory abnormalities. Pattern and frequency of adverse events revealed no substantial differences between both treatment groups.
Sunitinib treatment is feasible and moderately active in relapsed platinum-resistant ovarian cancer. The noncontinuous treatment schedule should be chosen for further studies in ovarian cancer.
复发性铂耐药卵巢癌通常对常规化疗疗效不佳，需要新的治疗方法。本Ⅱ期研究旨在评估舒尼替尼在铂耐药卵巢癌患者中的疗效，这些患者既往接受过最多三种化疗方案的治疗。
本随机Ⅱ期试验的主要终点是根据 RECIST 标准和/或妇科肿瘤学组 CA125 缓解标准评估舒尼替尼在复发性铂耐药卵巢癌患者中的客观缓解率，这些患者既往接受过最多三种化疗方案的治疗。采用选择设计比较了舒尼替尼两种方案（方案 1：50mg 舒尼替尼每日口服 28 天，随后停药 14 天；方案 2：37.5mg 舒尼替尼每日连续给药）。
73 例患者入组，其中 36 例患者被随机分配至非连续治疗组（方案 1），37 例患者被随机分配至连续治疗组（方案 2）。两组患者的平均年龄分别为 58.8 岁和 58.5 岁。方案 1 组观察到 6 例缓解者（完全缓解+部分缓解）（16.7%），方案 2 组观察到 2 例缓解者（5.4%）。方案 1 组的中位无进展生存期（4.8[2.9-8.1]个月）和总生存期（13.6[7.0-23.2]个月）与方案 2 组无显著差异（中位无进展生存期：2.9[2.9-5.1]个月；中位总生存期：13.7[8.4-25.6]个月）。不良反应包括乏力以及心血管、胃肠道和腹部症状、血液学和肝脏实验室异常。两组治疗组的不良反应类型和频率无显著差异。
舒尼替尼治疗复发性铂耐药卵巢癌是可行的，且具有一定的活性。在卵巢癌中应选择非连续治疗方案进行进一步研究。
