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JOIN 试验:接受改良 FOLFOX6 辅助治疗 II/III 期结肠癌患者在 3 年随访期间外周感觉神经病变的治疗结果和恢复状况。

JOIN trial: treatment outcome and recovery status of peripheral sensory neuropathy during a 3-year follow-up in patients receiving modified FOLFOX6 as adjuvant treatment for stage II/III colon cancer.

机构信息

Department of Gastroenterology and Gastrointestinal Oncology, National Cancer Center Hospital East, 6-5-1 Kashiwanoha, Kashiwa, 277-8577, Japan.

Gastrointestinal Cancer Center, Sano Hospital, Kobe, 655-0031, Japan.

出版信息

Cancer Chemother Pharmacol. 2019 Dec;84(6):1269-1277. doi: 10.1007/s00280-019-03957-5. Epub 2019 Sep 23.


DOI:10.1007/s00280-019-03957-5
PMID:31549217
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6820589/
Abstract

PURPOSE: Adjuvant FOLFOX therapy is an established standard-of-care for resected colon cancer. Peripheral sensory neuropathy (PSN) is regarded as the major toxicity issue related to FOLFOX therapy. There have been a few reports on the recovery status from PSN thereafter. JOIN trial investigated the tolerability and efficacy of adjuvant modified FOLFOX6 (mFOLFOX6) in Japanese patients with stage II/III colon cancer. METHODS: Twelve cycles of mFOLFOX6 were given to patients with stage II/III curatively resected colon cancer. Treatment outcomes, including disease-free survival (DFS), relapse-free survival (RFS), overall survival (OS), and recovery status of PSN during 3-year follow-up, were investigated. RESULTS: Of the 882 patients enrolled from 2010 to 2012, 864 were eligible for the efficacy analyses. Three-year DFS, RFS, and OS were favorable in 92.1, 92.8, and 97.4% of stage II patients; 76.4, 77.9, and 93.8% of stage IIIA/B; and 61.6, 62.7, and 85.9% of stage IIIC, respectively. The cumulative incidence of PSN during treatment was 47.8% in grade 1 (G1), 30.3% in G2, and 5.8% in G3. For those with G3 PSN during treatment, there was gradual recovery in 1.1% of patients at 12 months after enrollment, 0.5% at 24 months, and 0.2% at 36 months. However, G1 or G2 residual PSN after 3 years was observed in 21.0% (18.7%, G1; 2.3%, G2). CONCLUSIONS: Adjuvant mFOLFOX6 therapy was effective and well tolerated in patients with stage II/III colon cancer. Most patients recovered from G3 PSN related to oxaliplatin, but approximately 20% of patients had G1 or G2 PSN at 3-year follow-up.

摘要

目的:辅助 FOLFOX 疗法是结直肠癌切除后的标准治疗方法。周围感觉神经病变(PSN)被认为是与 FOLFOX 治疗相关的主要毒性问题。此后有一些关于 PSN 恢复状况的报告。JOIN 试验研究了辅助改良 FOLFOX6(mFOLFOX6)在日本 II/III 期结肠癌患者中的耐受性和疗效。

方法:对 II/III 期根治性切除的结肠癌患者给予 12 个周期的 mFOLFOX6 治疗。研究了无病生存(DFS)、无复发生存(RFS)、总生存(OS)以及 3 年随访期间 PSN 的恢复状况等治疗结局。

结果:2010 年至 2012 年共纳入 882 例患者,864 例患者符合疗效分析标准。II 期患者 3 年 DFS、RFS 和 OS 分别为 92.1%、92.8%和 97.4%;IIIA/B 期分别为 76.4%、77.9%和 93.8%;IIIC 期分别为 61.6%、62.7%和 85.9%。治疗期间 PSN 的累积发生率为 1 级(G1)47.8%,2 级(G2)30.3%,3 级(G3)5.8%。对于治疗期间出现 G3 PSN 的患者,12 个月时 enrolment 后有 1.1%的患者逐渐恢复,24 个月时为 0.5%,36 个月时为 0.2%。然而,3 年后仍有 21.0%(G1:18.7%;G2:2.3%)的患者存在 G1 或 G2 残留 PSN。

结论:辅助 mFOLFOX6 治疗对 II/III 期结肠癌患者有效且耐受良好。大多数患者从与奥沙利铂相关的 G3 PSN 中恢复,但约 20%的患者在 3 年随访时仍存在 G1 或 G2 PSN。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1c98/6820589/0a7686b26115/280_2019_3957_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1c98/6820589/8ccb0c51f01f/280_2019_3957_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1c98/6820589/0293e9553362/280_2019_3957_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1c98/6820589/346f25f82812/280_2019_3957_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1c98/6820589/0a7686b26115/280_2019_3957_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1c98/6820589/8ccb0c51f01f/280_2019_3957_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1c98/6820589/0293e9553362/280_2019_3957_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1c98/6820589/346f25f82812/280_2019_3957_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1c98/6820589/0a7686b26115/280_2019_3957_Fig4_HTML.jpg

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本文引用的文献

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Initial safety report on the tolerability of modified FOLFOX6 as adjuvant therapy in patients with curatively resected stage II or III colon cancer (JFMC41-1001-C2: JOIN trial).

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