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中华临床医师杂志(电子版)

中华临床医师杂志(电子版) ›› 2019, Vol. 13 ›› Issue (12) : 881 -887. doi: 10.3877/cma.j.issn.1674-0785.2019.12.001

所属专题： 文献；

临床研究

奥沙利铂联合卡培他滨在局部进展期直肠癌术前同步放化疗中的应用
石晨1, 张扬子1, 耿建昊1, 蔡勇1, 李永恒1,†(), 王维虎1,†()   
  1. 1. 100142　北京大学肿瘤医院暨北京市肿瘤防治研究所放射治疗科，恶性肿瘤发病机制及转化研究教育部重点实验室
  • 收稿日期:2019-04-12 出版日期:2019-06-15
  • 通信作者: 李永恒, 王维虎
  • 基金资助:
    北京市医院管理局青年人才培养"青苗"计划(QML20171104)

Application of oxaliplatin combined with capecitabine in preoperative concurrent chemoradiotherapy for locally advanced rectal cancer

Chen Shi1, Yangzi Zhang1, Jianhao Geng1, Yong Cai1, Yongheng Li1,†(), Weihu Wang1,†()   

  1. 1. Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Radiation Oncology, Peking University Cancer Hospital and Institute, Beijing 100142, China
  • Received:2019-04-12 Published:2019-06-15
  • Corresponding author: Yongheng Li, Weihu Wang
  • About author:
    Corresponding author: Li Yongheng, Email:
    Wang Weihu, Email:
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引用本文：

石晨, 张扬子, 耿建昊, 蔡勇, 李永恒, 王维虎. 奥沙利铂联合卡培他滨在局部进展期直肠癌术前同步放化疗中的应用[J]. 中华临床医师杂志(电子版), 2019, 13(12): 881-887.

Chen Shi, Yangzi Zhang, Jianhao Geng, Yong Cai, Yongheng Li, Weihu Wang. Application of oxaliplatin combined with capecitabine in preoperative concurrent chemoradiotherapy for locally advanced rectal cancer[J]. Chinese Journal of Clinicians(Electronic Edition), 2019, 13(12): 881-887.

目的

对奥沙利铂联合卡培他滨的术前同步化疗方案在高危局部进展期直肠癌中的安全性和有效性进行分析评价。

方法

对2018年3月至2019年2月，病理诊断明确，分期为T3~4或N+M0（距肛缘≤10 cm），于北京大学肿瘤医院行术前放疗的高危局部进展期直肠腺癌患者进行回顾性分析。纳入分析的患者至少具有以下高危因素之一：极低位，临床T分期为T4b，治疗前盆腔MRI提示直肠系膜筋膜受累或肠壁外静脉浸润阳性，侧方淋巴结受累。术前放疗采用同步加量调强放疗技术，处方剂量：95%计划肿瘤靶体积50.6 Gy/95%计划靶体积41.8 Gy，22f，30 d，每天1次。同步化疗为奥沙利铂联合卡培他滨双周方案，具体：每2周静脉滴注奥沙利铂85 mg/m2＋放疗日每日2次口服卡培他滨825 mg/m2。主要观察指标为肿瘤完全缓解（病理完全缓解＋临床完全缓解）率，次要观察指标包括：放化疗不良反应及术后并发症发生率，手术R0切除率、保肛率，肿瘤消退率、降期率，复发转移率等。

结果

共63例患者纳入分析，63例（100%）完成全部放疗剂量，50例（79.37%）完成全部3周期化疗。未观察到4级放化疗急性不良反应，5例（7.94%）发生3级不良反应。46例患者接受根治性手术，R0切除率为100%，手术保肛率为73.91%（36/46）。肿瘤完全缓解率为34.92%（22/63）。T、N降期率分别为82.61%（38/46）、95.65%（44/46）；肿瘤消退分级0、1、2级分别为30.43%（14/46）、45.65%（21/46）、23.91%（11/46）。6例出现术后并发症，均经保守治疗好转。中位随访时间7.2个月，随访过程中未出现患者死亡及局部复发，4例（6.35%，4/63）出现远处转移。

结论

对于高危局部进展期直肠癌患者，奥沙利铂联合卡培他滨的双药同步放化疗方案具有良好的近期疗效和可接受的不良反应，可能是更佳的新辅助治疗选择。

关键词: 直肠肿瘤, 抗肿瘤联合化疗方案, 奥沙利铂, 卡培他滨
Objective

To assess the efficacy and safety of oxaliplatin combined with capecitabine in preoperative concurrent chemoradiotherapy for high-risk locally advanced rectal cancer.

Methods

We retrospectively screened patients with locally advanced adenocarcinoma of the rectum (T3 or T4 with any N, or any T with node positivity) in Peking University Cancer Hospital and Institute from March 2018 to February 2019. The eligible patients had at least one of the following high-risk factors: very low cancer, clinical T4b, mesorectal fascia involvement, positive extramural venous invasion, and lateral lymph node involvement. The patients received preoperative intensity-modulated radiotherapy (95% planning gross tumor volume 50.6 Gy/95% planning target volume 41.8 Gy/22 f/30 d, a single fraction per day) with concurrent oxaliplatin 85 mg/m2 at d1 per two weeks and capecitabine 825 mg/m2 twice daily for 5 days per week. The primary outcome was complete response (clinical and pathologic complete response) rate. Secondary outcomes included adverse reactions, postoperative complications, R0 resection rate, anus-preserving operation rate, down-staging rate, tumor regression grade (TRG), local recurrence rate, and distant metastasis rate.

Results

In total, 63 patients were included in the analysis. Among them, 63 (100%) completed all radiotherapy doses, and 50 (79.37%) received all three cycles of chemotherapy. There were no cases of grade 4 adverse reactions, and grade 3 adverse reactions occurred in 5 (7.94%) cases. Of 46 patients who underwent surgery, the R0 resection rate was 100%, and the anus-preserving operation rate was 73.91% (36/46). The complete response rate was 34.92% (22/63). The T and N down-staging rates were 82.61% (38/46) and 95.65% (44/46), respectively. The percentages of cases with TRG 0, 1, and 2 were 30.43% (14/46), 45.65% (21/46), and 23.91% (11/46), respectively. Postoperative complications occurred in 6 cases, all of which were relieved by conservative treatments. The median follow-up time was 7.2 months. There was no death or local recurrence during follow-up, and 4 (6.35%, 4/63) cases had distant metastasis.

Conclusion

For patients with high-risk locally advanced rectal cancer, oxaliplatin combined with capecitabine in concurrent chemoradiotherapy has good short-term efficacy and acceptable adverse reactions, which may be a better candidate for neoadjuvant therapy.

Key words: Rectal neoplasms, Antineoplastic combined chemotherapy protocols, Oxaliplatin, Capecitabine
表1 63例直肠癌患者临床特征
临床特征 数据
性别［例（%）］ ?
? 男 45（71.43）
? 女 18（28.57）
年龄［岁，M（QR）］ 57（40~70）
肿瘤病理及分化［例（%）］ ?
? 高分化腺癌 4（6.35）
? 中分化腺癌 44（69.84）
? 低分化腺癌 6（9.52）
? 印戒细胞癌 2（3.17）
? 腺癌 7（11.11）
临床T分期［例（%）］ ?
? T2 1（1.58）
? T3 44（69.84）
? T4 18（28.57）
临床N分期［例（%）］ ?
? N0 2（3.17）
? N1 10（15.87）
? N2 51（80.95）
高危因素［例（%）］ ?
? 极低位 35（55.56）
? cT4b 11（17.46）
? 侧方淋巴结阳性 38（60.32）
? MRF阳性 29（46.03）
? EMVI阳性 24（38.10）
? 同时具有2个及以上高危因素 40（63.49）
ECOG评分［例（%）］ ?
? 0分 46（73.02）
? 1分 17（26.98）
表2 放化疗急性不良反应情况（例）
不良反应 0级 1级 2级 3级
白细胞减低 24 25 13 1
中性粒细胞减低 49 10 3 1
血小板减低 57 3 2 1
贫血 55 7 1 0
转氨酶升高 42 17 3 1
胆红素升高 58 5 0 0
乏力 28 33 2 0
放射性直肠炎 11 30 21 1
腹泻 54 6 2 1
会阴部皮肤反应 28 27 7 1
泌尿系反应 39 22 2 0
恶心、呕吐 27 31 5 0
手足综合征 61 2 0 0
神经毒性 53 10 0 0
表3 46例接受根治性手术患者情况
手术情况 数据
放疗-手术间隔［d，M（QR）］ 77（56~99）
手术方式［例（%）］ ?
? 直肠癌低位前切除术 31（67.39）
? 腹会阴联合切除术 12（26.09）
? 经肛门局部切除术 3（6.52）
手术保肛［例（%）］ 34（73.91）
低位手术保肛［例（%）］ 12（54.55）
R0切除［例（%）］ 46（100）
表4 46例接受根治性手术患者术后并发症情况
手术并发症 例（%）
吻合口瘘/出血 2（4.35）
盆腔感染/脓肿 1（2.17）
肠梗阻 1（2.17）
会阴伤口感染 2（4.35）
肺部感染 1（2.17）
新发房颤 1（2.17）
并发症治疗 ?
? 保守治疗 6/6（100）
? 手术治疗 0/6（0）
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