Division of Palliative and Supportive Care, Seirei Mikatahara General Hospital, 3453 Mikatahara-cho, Kita-ku, Hamamatsu, Shizuoka, 433-8558, Japan.
Seirei Hospice, Seirei Mikatahara General Hospital, Hamamatsu, Japan.
BMC Cancer. 2022 Feb 28;22(1):218. doi: 10.1186/s12885-022-09336-3.
Malignant ascites often causes discomfort in advanced cancer patients. Paracentesis is the most common treatment modality, but it requires frequently repeated treatment. Cell-free and concentrated ascites reinfusion therapy (CART) may prolong the paracentesis interval, but controlled trials are lacking. We assessed the feasibility of a randomized controlled trial of CART vs. paracentesis alone for patients with refractory malignant ascites.
This study was an open-label, fast-track, randomized controlled, feasibility trial. Patients admitted to four designated cancer hospitals who received no further anticancer treatments were eligible. Patients were randomly assigned 1:1 to a CART arm or control (simple paracentesis) arm. The feasibility endpoint was the percentage of patients who completed the study intervention. Secondary endpoints included paracentesis-free survival, patient's request on the questionnaire for paracentesis (PRO-paracentesis)-free survival (the period until the patients first reported that they would want paracentesis if indicated), and adverse events.
We screened 953 patients for eligibility. Of 61 patients with refractory malignant ascites, 21 patients were determined as eligible. Finally, 20 patients consented and were allocated; 18 patients (90%, 95% CI: 68.3-98.8) completed the study intervention. All patients had an ECOG performance status of 3 or 4. The median drained ascites volume was 3,200 mL in the CART arm and 2,500 mL in the control arm. In the CART arm, the median reinfused albumin volume was 12.6 g. Median paracentesis-free survivals were 5 days (95% CI: 2-6) in the CART arm, and 6 days (3-9) in the control arm. Median PRO-paracentesis-free survivals were 4 days (2-5) and 5 days (1-9), respectively. A total of 73% of patients received paracentesis within 2 days from their first request for the next paracentesis. One patient in the CART arm developed Grade 1 fever.
A fast-track randomized controlled trial of CART for patients with malignant ascites is feasible. The efficacy and safety of CART should be assessed in future trials. PRO-paracentesis-free survival may be a complementary outcome measure with paracentesis-free survival in future trials.
Registered at University Hospital Medical Information Network Clinical Trial Registry as UMIN000031029 . Registered on 28/01/2018.
恶性腹水常导致晚期癌症患者不适。腹腔穿刺术是最常见的治疗方式，但需要频繁重复治疗。无细胞和浓缩腹水再输注治疗（CART）可能会延长腹腔穿刺术的间隔时间，但缺乏对照试验。我们评估了 CART 与单纯腹腔穿刺术治疗难治性恶性腹水的随机对照试验的可行性。
这是一项开放标签、快速通道、随机对照的可行性试验。在四个指定的癌症医院住院且未接受进一步抗癌治疗的患者符合入选条件。患者按 1:1 随机分配至 CART 组或对照组（单纯腹腔穿刺术）。可行性终点是完成研究干预的患者百分比。次要终点包括无腹腔穿刺术生存、患者对腹腔穿刺术调查问卷（PRO-paracentesis）的需求（无腹腔穿刺术生存，即患者首次报告如果需要则希望进行腹腔穿刺术的时间）和不良事件。
我们对 953 名患者进行了资格筛选。在 61 名难治性恶性腹水患者中，有 21 名患者被确定符合入选条件。最终，有 20 名患者同意并接受了分配；18 名患者（90%，95%CI：68.3-98.8）完成了研究干预。所有患者的 ECOG 表现状态均为 3 或 4 级。CART 组的中位引流腹水体积为 3200ml，对照组为 2500ml。在 CART 组，中位再输注白蛋白体积为 12.6g。CART 组的中位无腹腔穿刺术生存时间为 5 天（95%CI：2-6），对照组为 6 天（3-9）。中位 PRO-paracentesis-free 生存时间分别为 4 天（2-5）和 5 天（1-9）。73%的患者在首次要求下一次腹腔穿刺术的 2 天内接受了腹腔穿刺术。CART 组有 1 例患者出现 1 级发热。
恶性腹水患者的 CART 快速通道随机对照试验是可行的。应在未来的试验中评估 CART 的疗效和安全性。在未来的试验中，PRO-paracentesis-free 生存可能是与无腹腔穿刺术生存互补的结局指标。
在大学医院医学信息网络临床试验注册中心注册，注册号为 UMIN000031029。于 2018 年 1 月 28 日注册。
