Gastroenterological Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Department of Surgery and Science Faculty of Medicine, Academic Assembly, University of Toyama, Toyama, Japan.
Br J Surg. 2020 Dec;107(13):1811-1817. doi: 10.1002/bjs.11792. Epub 2020 Jul 7.
Intraperitoneal chemotherapy using paclitaxel is considered an experimental approach for treating peritoneal carcinomatosis. This study aimed to determine the recommended dose, and to evaluate the clinical efficacy and safety, of the combination of intravenous gemcitabine, intravenous nab-paclitaxel and intraperitoneal paclitaxel in patients with pancreatic cancer and peritoneal metastasis.
The frequencies of dose-limiting toxicities were evaluated, and the recommended dose was determined in phase I. The primary endpoint of the phase II analysis was overall survival rate at 1 year. Secondary endpoints were antitumour effects, symptom-relieving effects, safety and overall survival.
The recommended doses of intravenous gemcitabine, intravenous nab-paclitaxel and intraperitoneal paclitaxel were 800, 75 and 20 mg/m respectively. Among 46 patients enrolled in phase II, the median time to treatment failure was 6·0 (range 0-22·6) months. The response and disease control rates were 21 of 43 and 41 of 43 respectively. Ascites disappeared in 12 of 30 patients, and cytology became negative in 18 of 46. The median survival time was 14·5 months, and the 1-year overall survival rate was 61 per cent. Conversion surgery was performed in eight of 46 patients, and those who underwent resection survived significantly longer than those who were not treated surgically (median survival not reached versus 12·4 months). Grade 3-4 haematological toxicities developed in 35 of 46 patients, whereas non-haematological adverse events occurred in seven patients.
Adding intraperitoneal paclitaxel had clinical efficacy with acceptable tolerability.
腹腔内给予紫杉醇化疗被认为是治疗腹膜癌病的一种实验性方法。本研究旨在确定静脉注射吉西他滨、静脉注射白蛋白结合型紫杉醇和腹腔内给予紫杉醇联合方案治疗胰腺癌伴腹膜转移患者的推荐剂量，并评估其临床疗效和安全性。
在 I 期研究中评估剂量限制性毒性的发生频率，并确定推荐剂量。II 期分析的主要终点为 1 年总生存率。次要终点为抗肿瘤疗效、症状缓解效果、安全性和总生存率。
静脉注射吉西他滨、静脉注射白蛋白结合型紫杉醇和腹腔内给予紫杉醇的推荐剂量分别为 800、75 和 20mg/m2。在 46 例入组 II 期研究的患者中，中位无进展生存期为 6.0（0-22.6）个月。客观缓解率和疾病控制率分别为 21/43 和 41/43。30 例患者中有 12 例腹水消失，46 例患者中有 18 例细胞学转阴。中位总生存期为 14.5 个月，1 年总生存率为 61%。46 例患者中有 8 例接受了转化手术，接受手术切除的患者的生存时间明显长于未接受手术治疗的患者（中位生存期未达到 vs. 12.4 个月）。46 例患者中有 35 例发生 3-4 级血液学毒性，7 例发生非血液学不良事件。
腹腔内给予紫杉醇具有临床疗效且可耐受。
