Department of Gastrointestinal Surgery, The Affiliated Ganzhou Hospital of Nanchang University.
Department of Medical Oncology, The Affiliated Ganzhou Hospital of Nanchang University.
Biol Pharm Bull. 2024;47(10):1675-1681. doi: 10.1248/bpb.b24-00422.
In this trial, the feasibility and efficacy of neoadjuvant chemotherapy with targeted agents in the treatment of patients with locally advanced rectal cancer were evaluated. In this single-center, prospective, randomized controlled trial, we randomly assigned (1 : 1) patients with locally advanced rectal cancer with wild-type RAS/BRAF gene to two groups: 5 cycles of modified leucovorin calcium (folinic acid), fluorouracil, and oxaliplatin combination regimen (modified FOLFOX6, mFOLFOX6) concurrent with 25 times radiotherapy or 5 cycles of mFOLFOX6 plus cetuximab, all with subsequent total mesorectal excision (TME) resection and adjuvant chemotherapy. We performed a random assignment by a computer-generated random number sequence. The primary end point was the R0 resection rate. The secondary end points were rates of pathologic complete response, downstaging, adverse events, postoperative complications, preventive enterostomy and low anterior resection syndrome. From January 6, 2020 to October 28, 2022, 80 patients were assigned and evaluated. In the mFOLFOX6-RT and mFOLFOX6-Cet groups, the rate of R0 resection was 96.7 and 96.9% (p = 1.000); the rate of pathological complete response (pCR) was 23.3 and 21.9% (p = 0.891); and the rate of downstaging (ypStage 0 to 1) was 53.3 and 53.1% (p = 1.000), respectively. No statistical differences between the two groups were observed in the incidence of adverse events and postoperative complications. Additionally, lower rates of preventive enterostomy and low anterior resection syndrome were shown in the mFOLFOX6-Cet group compared to the mFOLFOX6-RT group. The neoadjuvant treatment strategy of mFOLFOX6 with cetuximab is feasible and promising for patients with locally advanced rectal cancer, even superior to mFOLFOX6 with radiotherapy.
在这项试验中，评估了靶向药物新辅助化疗治疗局部晚期直肠癌患者的可行性和疗效。在这项单中心、前瞻性、随机对照试验中，我们将野生型 RAS/BRAF 基因的局部晚期直肠癌患者随机分为两组：5 个周期改良的亚叶酸钙（叶酸）、氟尿嘧啶和奥沙利铂联合方案（改良 FOLFOX6，mFOLFOX6）联合 25 次放疗或 5 个周期 mFOLFOX6 加西妥昔单抗，均随后进行全直肠系膜切除术（TME）切除和辅助化疗。我们通过计算机生成的随机数序列进行随机分组。主要终点是 R0 切除率。次要终点是病理完全缓解率、降期率、不良事件、术后并发症、预防性造口术和低位前切除术综合征。从 2020 年 1 月 6 日至 2022 年 10 月 28 日，共纳入 80 例患者并进行评估。在 mFOLFOX6-RT 和 mFOLFOX6-Cet 组中，R0 切除率分别为 96.7%和 96.9%（p=1.000）；病理完全缓解率（pCR）分别为 23.3%和 21.9%（p=0.891）；降期率（ypStage 0 至 1）分别为 53.3%和 53.1%（p=1.000）。两组不良事件和术后并发症发生率无统计学差异。此外，mFOLFOX6-Cet 组预防性造口术和低位前切除术综合征的发生率均低于 mFOLFOX6-RT 组。mFOLFOX6 联合西妥昔单抗的新辅助治疗策略对于局部晚期直肠癌患者是可行且有前途的，甚至优于 mFOLFOX6 联合放疗。
