Department of Gastroenterological Surgery, Gifu University Graduate School of Medicine, Gifu, Japan;
Department of Gastroenterological Surgery, Gifu University Graduate School of Medicine, Gifu, Japan.
Anticancer Res. 2021 Dec;41(12):6247-6257. doi: 10.21873/anticanres.15445.
BACKGROUND/AIM: We report the end results of a study evaluating the safety and efficacy of preoperative chemoradiotherapy with S-1 plus oxaliplatin.
Eligible patients had histopathologically confirmed locally advanced rectal carcinoma (LARC; cT3-T4, any N). They received oral S-1 (80 mg/m/day on days 1-5, 8-12, 22-26, and 29-33) and oxaliplatin by infusion (50 mg/m/day on days 1, 8, 22, and 29) along with radiotherapy (1.8 Gy/day, total dose: 45 Gy/25 fractions). A chemotherapy gap was included in the third week of radiotherapy. The study endpoint was pathological response rate (Grade 2, 3). Secondary endpoints included rates of pathologic complete response (pCR), R0 resection, disease-free survival (DFS), overall survival (OS), local and distant recurrence, and safety and relative dose intensity.
The study enrolled 23 patients at three Centres in Gifu, Japan. All patients received chemoradiotherapy, and 22 underwent surgery. Rates of pathological response, R0 resection, and pathological down-staging were 56.5% (13/23), 95.7% (22/23), and 63.6% (14/22), respectively. There were no grade 4 adverse events, but grade 3 events occurred in 21.7% of patients. The cumulative 3-year local recurrence rate was 8.7%. Distant metastasis occurred in 10 (43.5%) patients, 2 (8.7%) from local recurrence and 2 from secondary pancreatic cancer and lung cancer. There were 8 patients with lung metastasis, 2 with liver metastasis, one with ovarian metastasis, and one with bone metastasis. Three-year rates of DFS and OS were 51.1% (median follow-up 34.3 months) and 91.1% (45.2 months), respectively.
The study showed high pathological response rate without severe toxicity and good follow-up results. Unexpectedly, however, this regimen could not control local recurrence and distant metastasis. Nevertheless, adding oxaliplatin to preoperative chemoradiotherapy with S-1 in patients with LARC appears feasible and may safely result in better local control than standard treatment. The study suggests adding treatment with induction chemotherapy in consideration of CEA level and N factor.
背景/目的：我们报告了术前化疗联合 S-1 和奥沙利铂治疗的安全性和疗效研究的最终结果。
符合条件的患者均经组织病理学证实为局部晚期直肠癌（LARC；cT3-T4，任何 N）。他们接受口服 S-1（第 1-5 天、第 8-12 天、第 22-26 天和第 29-33 天，每天 80mg/m）和奥沙利铂静脉滴注（第 1、8、22 和 29 天，每天 50mg/m），同时接受放疗（1.8Gy/天，总剂量：45Gy/25 次）。在放疗的第三周包括一个化疗间隙。研究终点是病理反应率（Grade 2、3）。次要终点包括病理完全缓解率（pCR）、R0 切除率、无病生存率（DFS）、总生存率（OS）、局部和远处复发率以及安全性和相对剂量强度。
该研究在日本岐阜的三个中心招募了 23 名患者。所有患者均接受了放化疗，22 名患者接受了手术。病理反应、R0 切除率和病理降级率分别为 56.5%（23/23）、95.7%（22/23）和 63.6%（22/22）。没有 4 级不良事件，但有 21.7%的患者发生 3 级事件。3 年累积局部复发率为 8.7%。远处转移发生在 10 名（43.5%）患者中，2 名（8.7%）来自局部复发，2 名来自继发性胰腺癌和肺癌。有 8 名患者出现肺转移，2 名患者出现肝转移，1 名患者出现卵巢转移，1 名患者出现骨转移。3 年 DFS 和 OS 率分别为 51.1%（中位随访 34.3 个月）和 91.1%（45.2 个月）。
该研究显示，在没有严重毒性且随访结果良好的情况下，高病理反应率。然而，出乎意料的是，该方案无法控制局部复发和远处转移。然而，在 LARC 患者中，将奥沙利铂加入 S-1 的术前化疗似乎是可行的，并且可能安全地导致比标准治疗更好的局部控制。该研究表明，在考虑 CEA 水平和 N 因素的情况下，应添加诱导化疗。
