多中心、单臂、2 期临床试验（CRC-PIPAC）中，采用重复奥沙利铂腹腔内高压气溶胶化疗治疗孤立性不可切除结直肠腹膜转移患者的报告结局。
Patient-reported outcomes during repetitive oxaliplatin-based pressurized intraperitoneal aerosol chemotherapy for isolated unresectable colorectal peritoneal metastases in a multicenter, single-arm, phase 2 trial (CRC-PIPAC).
机构信息
Department of Surgery, Catharina Cancer Institute, PO Box 1350, 5602 ZA, Eindhoven, The Netherlands.
Department of Research and Development, Netherlands Comprehensive Cancer Organization, Utrecht, The Netherlands.
出版信息
Surg Endosc. 2022 Jun;36(6):4486-4498. doi: 10.1007/s00464-021-08802-6. Epub 2021 Nov 10.
BACKGROUND
CRC-PIPAC prospectively assessed repetitive oxaliplatin-based pressurized intraperitoneal aerosol chemotherapy (PIPAC-OX) as a palliative monotherapy (i.e., without concomitant systemic therapy in between subsequent procedures) for unresectable colorectal peritoneal metastases (CPM). The present study explored patient-reported outcomes (PROs) during trial treatment.
METHODS
In this single-arm phase 2 trial in two tertiary centers, patients with isolated unresectable CPM received 6-weekly PIPAC-OX (92 mg/m). PROs (calculated from EQ-5D-5L, and EORTC QLQ-C30 and QLQ-CR29) were compared between baseline and 1 and 4 weeks after the first three procedures using linear mixed modeling with determination of clinical relevance (Cohen's D ≥ 0.50) of statistically significant differences.
RESULTS
Twenty patients underwent 59 procedures (median 3 [range 1-6]). Several PROs solely worsened 1 week after the first procedure (index value - 0.10, p < 0.001; physical functioning - 20, p < 0.001; role functioning - 27, p < 0.001; social functioning - 18, p < 0.001; C30 summary score - 16, p < 0.001; appetite loss + 15, p = 0.007; diarrhea + 15, p = 0.002; urinary frequency + 13, p = 0.004; flatulence + 13, p = 0.001). These PROs returned to baseline at subsequent time points. Other PROs worsened 1 week after the first procedure (fatigue + 23, p < 0.001; pain + 29, p < 0.001; abdominal pain + 32, p < 0.001), second procedure (fatigue + 20, p < 0.001; pain + 21, p < 0.001; abdominal pain + 20, p = 0.002), and third procedure (pain + 22, p < 0.001; abdominal pain + 22, p = 0.002). Except for appetite loss, all changes were clinically relevant. All analyzed PROs returned to baseline 4 weeks after the third procedure.
CONCLUSIONS
Patients receiving repetitive PIPAC-OX monotherapy for unresectable CPM had clinically relevant but reversible worsening of several PROs, mainly 1 week after the first procedure.
TRIAL REGISTRATION
Clinicaltrials.gov: NCT03246321; Netherlands trial register: NL6426.
背景
CRC-PIPAC 前瞻性评估重复奥沙利铂基础腹腔内加压气溶胶化疗（PIPAC-OX）作为不可切除结直肠腹膜转移（CPM）的姑息性单药治疗（即在后续治疗过程中不联合全身治疗）。本研究探讨了试验治疗期间的患者报告结局（PRO）。
方法
在这两个三级中心的单臂 2 期试验中，患有孤立性不可切除的 CPM 的患者接受 6 周一次的 PIPAC-OX（92mg/m）。使用线性混合模型，从 EQ-5D-5L、EORTC QLQ-C30 和 QLQ-CR29 中计算 PRO（基线与第一次三程序后 1 周和 4 周），并确定具有统计学意义差异的临床相关性（Cohen's D≥0.50）。
结果
20 名患者进行了 59 次治疗（中位数 3[范围 1-6]）。仅在第一次治疗后 1 周时，几项 PRO 恶化（指数值-0.10，p<0.001；身体功能-20，p<0.001；角色功能-27，p<0.001；社会功能-18，p<0.001；C30 综合评分-16，p<0.001；食欲减退+15，p=0.007；腹泻+15，p=0.002；尿频+13，p=0.004；气胀+13，p=0.001）。这些 PRO 在后续时间点恢复到基线。其他 PRO 在第一次治疗后 1 周时恶化（疲劳+23，p<0.001；疼痛+29，p<0.001；腹痛+32，p<0.001），第二次治疗（疲劳+20，p<0.001；疼痛+21，p<0.001；腹痛+20，p=0.002）和第三次治疗（疼痛+22，p<0.001；腹痛+22，p=0.002）。除了食欲减退，所有变化都具有临床意义。所有分析的 PRO 在第三次治疗后 4 周恢复到基线。
结论
接受不可切除 CPM 重复 PIPAC-OX 单药治疗的患者的几个 PRO 出现具有临床意义但可逆转的恶化，主要是在第一次治疗后 1 周。
试验注册
Clinicaltrials.gov：NCT03246321；荷兰试验注册处：NL6426。
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