[Preliminary analysis of mFOLFOXIRI plus bevacizumab combined with cytoreductive surgery for resectable peritoneal metastases from colorectal cancer: a prospective,randomized phase II clinical trial].
Researchers
H M Liu, H B Hu, Y Y Kuang, Z T Lin, K L Yang, H Wang
Abstract
<b>Objective:</b> To investigate the efficacy and safety of mFOLFOXIRI combined with bevacizumab plus cytoreductive surgery (CRS) in patients with resectable peritoneal metastasis of colorectal cancer (CRC). <b>Methods:</b> A single-center, prospective randomized controlled design was conducted. Inclusion criteria: confirmed synchronous or metachronous peritoneal metastasis of CRC, aged >18 years, adequate organ function and tolerance to chemotherapy, resectable peritoneal lesions with peritoneal cancer index (PCI) <20, Eastern Cooperative Oncology Group (ECOG) performance status score of 0-1, and tolerance to CRS. Exclusion criteria: intolerance or inefficacy to oxaliplatin, distant unresectable metastasis, emergency surgery, active malignancy, history of thromboembolism, pregnancy or lactation, and other severe comorbidities. Between August 2022 and December 2024, eligible patients with resectable peritoneal metastasis of CRC treated at the Sixth Affiliated Hospital, Sun Yat-sen University were enrolled and randomly assigned at a 1:1 ratio to the neoadjuvant therapy group (mFOLFOXIRI plus bevacizumab followed by CRS) or the direct CRS group. The primary endpoint was the 1-year progression-free survival rate. Secondary endpoints included the response to neoadjuvant therapy, completeness of cytoreduction (CC) score, length of postoperative hospital stay, and postoperative complications. <b>Results:</b> A total of 53 patients who underwent surgery were included, with 19 in the neoadjuvant therapy group and 34 in the direct CRS group. There were no statistically significant differences between the two groups in age, sex, BMI, primary tumor location, pathological type, pattern of peritoneal metastasis (synchronous/metachronous), extraperitoneal metastasis, history of prior systemic therapy, baseline radiological PCI score, or tumor markers (CEA, CA19-9, CA125) (all <i>P</i>>0.05). In the neoadjuvant therapy group, post-treatment radiological PCI score was significantly lower than baseline [<i>M</i>(<i>Q</i><sub>1</sub>,<i>Q</i><sub>3</sub>): 6.0 (4.0, 12.0) vs. 8.0 (5.0, 12.0), <i>Z</i>=-3.086, <i>P</i>=0.002], and CEA was significantly reduced [3.9 (2.8, 7.3) μg/L vs. 7.7 (4.1, 16.1) μg/L, <i>Z</i>=-2.809, <i>P</i>=0.005]. Hemoglobin and albumin levels were also decreased [107.0 (97.5, 117.0) g/L vs. 134.0 (118.0, 140.5) g/L, <i>Z</i>=-3.019, <i>P</i>=0.003;35.9 (34.9, 39.3) g/L vs. 40.0 (37.3, 42.9) g/L, <i>Z</i>=-2.213, <i>P</i>=0.027], with all differences statistically significant (all <i>P</i><0.05). CA19-9 and CA125 showed a downward trend, but the differences were not statistically significant (all <i>P</i>>0.05). There were no significant between-group differences in CC grade (proportion of CC 0-1: 17/19 vs. 88.2% [30/34]), length of postoperative hospital stay [10.0 (7.0, 13.0) days vs. 13.0 (9.3, 14.0) days], or incidence of severe postoperative complications (8/19 vs. 38.2%[13/34]) (all <i>P</i>>0.05). The proportion of 1-year progression-free survival in the neoadjuvant therapy group was 10/19, which was higher than that in the direct CRS group (29.4%), but the difference was not statistically significant (<i>χ</i>²=2.797, <i>P</i>=0.096). <b>Conclusion:</b> Neoadjuvant therapy with mFOLFOXIRI plus bevacizumab can reduce peritoneal tumor burden without increasing surgical risk, and may improve progression-free survival. However, due to the small sample size and short follow-up duration, long-term benefits need to be confirmed by further follow-up. <b>目的：</b> 探讨mFOLFOXIRI+贝伐珠单抗联合肿瘤细胞减灭术（CRS）在可切除结直肠癌（CRC）腹膜转移患者中的疗效与安全性。 <b>方法：</b> 采用单中心、前瞻性随机对照设计。纳入标准：确诊同时性或异时性CRC腹膜转移，>18岁，脏器功能达标、可耐受化疗，腹膜病灶可切除［腹膜癌指数（PCI）<20］，东部肿瘤协作组体力状态评分（0~1）分，可耐受CRS。排除标准：奥沙利铂不耐受或无效，伴远处不可切除的转移、急诊手术、活动性肿瘤、血栓史、妊娠哺乳或存在其他严重疾病。根据以上标准，纳入2022年8月至2024年12月期间中山大学附属第六医院收治的可切除CRC腹膜转移患者，按1∶1随机分为新辅助治疗组（mFOLFOXIRI+贝伐珠单抗新辅助治疗后行CRS）与直接CRS组。主要观察指标为1年无进展生存比例，次要观察指标包括新辅助治疗的疗效、细胞减灭程度（CC）、术后住院时间以及术后并发症。 <b>结果：</b> 共纳入53例已接受手术的患者，其中新辅助治疗组19例，直接CRS组34例。两组患者在年龄、性别、体质指数、原发肿瘤部位、病理类型、腹膜转移类型（同时性/异时性）、是否合并腹膜外转移、既往系统治疗史、基线影像学PCI评分以及肿瘤标志物［癌胚抗原（CEA）、糖类抗原（CA）-19-9和CA125］等方面的差异均无统计学意义（均<i>P</i>>0.05）。新辅助治疗组的新辅助治疗前后的比较结果显示，相比治疗前，治疗后患者影像学PCI评分明显下降［<i>M</i>（<i>Q</i><sub>1</sub>，<i>Q</i><sub>3</sub>）：6.0（4.0，12.0）分比8.0（5.0，12.0），<i>Z=</i>-3.086，<i>P</i>=0.002］，CEA明显降低［3.9（2.8，7.3）μg/L比7.7（4.1，16.1）μg/L，<i>Z=</i>-2.809，<i>P</i>=0.005］，同时血红蛋白及白蛋白水平也降低［分别为107.0（97.5，117.0）g/L比134.0（118.0，140.5）g/L，<i>Z=</i>-3.019，<i>P</i>=0.003；35.9（34.9，39.3）g/L比40.0（37.3，42.9）g/L，<i>Z=</i>-2.213，<i>P</i>=0.027］，差异均有统计学意义（均<i>P</i><0.05）。CA19-9以及CA125水平也具有下降趋势，但差异均未达到统计学意义（均<i>P</i>>0.05）。两组患者CC程度［CC 0~1比例：17/19比88.2%（30/34）］、术后住院时间［10.0（7.0，13.0）d比13.0（9.3，14.0）d］以及术后严重并发症的发生率［8/19比38.2%（13/34）］比较，差异均无统计学意义（均<i>P</i>>0.05）。新辅助治疗组1年无进展生存患者比例为10/19，高于直接CRS组（29.4%），但差异未达到统计学意义（<i>χ</i><sup>2</sup>=2.797，<i>P</i>=0.096）。 <b>结论：</b> mFOLFOXIRI+贝伐珠单抗新辅助治疗可降低腹膜肿瘤负荷，并未增加手术风险，且可能改善患者无进展生存期，但鉴于本研究目前纳入样本量小，随访时间短，其长期获益仍需进一步随访验证。.Source: PubMed (PMID: 42045712)View Original on PubMed