Department of Surgery, Catharina Cancer Institute, Eindhoven, The Netherlands.
Department of Surgery, St. Antonius Hospital, Nieuwegein, The Netherlands.
Ann Surg Oncol. 2021 Sep;28(9):5311-5326. doi: 10.1245/s10434-020-09558-4. Epub 2021 Feb 5.
Despite its increasing use, pressurized intraperitoneal aerosol chemotherapy with oxaliplatin (PIPAC-OX) has never been prospectively investigated as a palliative monotherapy for colorectal peritoneal metastases in clinical trials. This trial aimed to assess the safety (primary aim) and antitumor activity (key secondary aim) of PIPAC-OX monotherapy in patients with unresectable colorectal peritoneal metastases.
In this two-center, single-arm, phase II trial, patients with isolated unresectable colorectal peritoneal metastases in any line of palliative treatment underwent 6-weekly PIPAC-OX (92 mg/m). Key outcomes were major treatment-related adverse events (primary outcome), minor treatment-related adverse events, hospital stay, tumor response (radiological, biochemical, pathological, ascites), progression-free survival, and overall survival.
Twenty enrolled patients underwent 59 (median 3, range 1-6) PIPAC-OX procedures. Major treatment-related adverse events occurred in 3 of 20 (15%) patients after 5 of 59 (8%) procedures (abdominal pain, intraperitoneal hemorrhage, iatrogenic pneumothorax, transient liver toxicity), including one possibly treatment-related death (sepsis of unknown origin). Minor treatment-related adverse events occurred in all patients after 57 of 59 (97%) procedures, the most common being abdominal pain (all patients after 88% of procedures) and nausea (65% of patients after 39% of procedures). Median hospital stay was 1 day (range 0-3). Response rates were 0% (radiological), 50% (biochemical), 56% (pathological), and 56% (ascites). Median progression-free and overall survival were 3.5 months (interquartile range [IQR] 2.5-5.7) and 8.0 months (IQR 6.3-12.6), respectively.
In patients with unresectable colorectal peritoneal metastases undergoing PIPAC-OX monotherapy, some major adverse events occurred and minor adverse events were common. The clinical relevance of observed biochemical, pathological, and ascites responses remains to be determined, especially since radiological response was absent.
尽管加压腹腔内气溶胶化疗联合奥沙利铂（PIPAC-OX）的应用日益增多，但在临床试验中，该方法从未被前瞻性地作为结直肠腹膜转移的姑息性单药治疗进行研究。本试验旨在评估 PIPAC-OX 单药治疗不可切除的结直肠腹膜转移患者的安全性（主要目的）和抗肿瘤活性（关键次要目的）。
在这项两中心、单臂、二期试验中，在姑息治疗的任何阶段均接受不可切除的结直肠腹膜转移的患者接受 6 周一次的 PIPAC-OX（92mg/m）治疗。主要结局为主要治疗相关不良事件（主要结局）、次要治疗相关不良事件、住院时间、肿瘤反应（影像学、生化、病理学、腹水）、无进展生存期和总生存期。
20 名入组患者共进行了 59 次（中位数 3 次，范围 1-6 次）PIPAC-OX 治疗。20 名患者中有 3 名（15%）在 59 次（8%）治疗中有 5 次（腹痛、腹腔内出血、医源性气胸、短暂性肝毒性）发生主要治疗相关不良事件，包括 1 例可能与治疗相关的死亡（不明原因的败血症）。所有患者在 57 次（97%）治疗后均发生了轻微的治疗相关不良事件，最常见的是腹痛（所有患者在 88%的治疗后）和恶心（65%的患者在 39%的治疗后）。中位住院时间为 1 天（范围 0-3 天）。影像学缓解率为 0%（生化缓解率为 50%，病理学缓解率为 56%，腹水缓解率为 56%。中位无进展生存期和总生存期分别为 3.5 个月（四分位距 [IQR] 2.5-5.7）和 8.0 个月（IQR 6.3-12.6）。
在接受 PIPAC-OX 单药治疗的不可切除的结直肠腹膜转移患者中，发生了一些严重的不良事件，轻微的不良事件很常见。观察到的生化、病理学和腹水反应的临床相关性仍有待确定，特别是因为没有影像学反应。
