Berek Jonathan S, Edwards Robert P, Parker Lynn P, DeMars Leslie R, Herzog Thomas J, Lentz Samuel S, Morris Robert T, Akerley Wallace L, Holloway Robert W, Method Michael W, Plaxe Steven C, Walker Joan L, Friccius-Quecke Hilke, Krasner Carolyn N
*Stanford Women's Cancer Center, Stanford Cancer Institute, Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Stanford University School of Medicine, Stanford, CA; †Magee Women's Hospital of UPMC, Pittsburgh, PA; ‡James Graham Brown Cancer Center, Louisville, KY; §Dartmouth-Hitchcock Medical Center, Lebanon, NH; ∥Columbia University Cancer Center, New York, NY; ¶WFU Baptist Medical Center, Winston-Salem, NC; #Barbara Ann Karmanos Cancer Center, Wayne State University, Detroit, MI; **Huntsman Cancer Institute, Salt Lake City, UT; ††Florida Hospital Cancer Institute, Orlando, FL; ‡‡Northern Indiana Cancer Research Consortium, South Bend, IN; §§University of California, San Diego, CA; ∥∥University of Oklahoma Health Science Center, Oklahoma City, OK; ¶¶Neovii Biotech GmbH (formerly Fresenius Biotech GmbH), Munich, Germany; ##Massachusetts General Hospital, Dana-Farber/Harvard Cancer Center, Boston, MA.
Int J Gynecol Cancer. 2014 Nov;24(9):1583-9. doi: 10.1097/IGC.0000000000000286.
The aim of this study was to investigate the efficacy and safety of intraperitoneal catumaxomab in heavily pretreated patients with chemotherapy-refractory ovarian cancer and recurrent symptomatic malignant ascites.
The study is a single-arm open-label multicenter US phase II study. Patients received 4 three-hour intraperitoneal catumaxomab infusions (10, 20, 50, and 150 μg within 10 days). The primary end point was the percentage of patients with at least a 4-fold increase in the puncture-free interval (PuFI) relative to the pretreatment interval. The main secondary end points were puncture-free survival, overall survival, ascites symptoms, and safety. Time to first therapeutic puncture (TTPu) was analyzed post hoc.
Forty patients were screened, and 32 patients (80%) were treated. Seven patients (23%) achieved the primary end point. The median PuFI was prolonged 2-fold from 12 to 27.5 days. The median TTPu was prolonged 4-fold from 12 to 52 days. The median puncture-free survival and overall survival were 29.5 and 111 days, respectively. Nineteen patients (59%) required puncture after catumaxomab treatment. Ascites symptoms improved in most of the 13 predefined categories. At study end, most symptoms were still improved compared with screening. The most frequent treatment-related adverse events were related to cytokine release (vomiting, nausea, pyrexia, fatigue, and chills) or intraperitoneal administration (abdominal pain). Transient increases in liver parameters and transient decreases in blood lymphocytes were regularly observed but were generally without clinical relevance.
Catumaxomab prolonged PuFI and TTPu had a beneficial effect on quality of life, as shown by the improvement in ascites symptoms, and had an acceptable safety profile, which is consistent with its mode of action.
本研究旨在探讨腹腔注射卡妥索单抗治疗经多程治疗的化疗难治性卵巢癌及复发性有症状恶性腹水患者的疗效和安全性。
本研究为单臂开放标签多中心美国II期研究。患者接受4次为期3小时的腹腔注射卡妥索单抗（10天内分别为10、20、50和150μg）。主要终点是相对于预处理间隔，穿刺无间隔期（PuFI）至少增加4倍的患者百分比。主要次要终点是穿刺无生存期、总生存期、腹水症状和安全性。首次治疗性穿刺时间（TTPu）进行事后分析。
40例患者接受筛查，32例患者（80%）接受治疗。7例患者（23%）达到主要终点。PuFI中位数从12天延长至27.5天，延长了2倍。TTPu中位数从12天延长至52天，延长了4倍。穿刺无生存期和总生存期的中位数分别为29.5天和111天。19例患者（59%）在卡妥索单抗治疗后需要穿刺。在13个预定义类别中，大多数患者的腹水症状有所改善。在研究结束时，与筛查相比，大多数症状仍有所改善。最常见的治疗相关不良事件与细胞因子释放（呕吐、恶心、发热、疲劳和寒战）或腹腔给药（腹痛）有关。定期观察到肝脏参数短暂升高和血液淋巴细胞短暂减少，但一般无临床意义。
卡妥索单抗延长了PuFI和TTPu，对生活质量有有益影响，如腹水症状改善所示，并且具有可接受的安全性，这与其作用方式一致。
