Pre-emptive oral clarithromycin reduces the skin toxicity of panitumumab treatment for metastatic colorectal cancer
Pre-emptive oral clarithromycin reduces the skin toxicity of panitumumab treatment for metastatic colorectal cancer
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预先口服克拉霉素可降低帕尼单抗治疗转移性结直肠癌的皮肤毒性
DOI：
10.1007/s00384-021-04002-9
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发表时间：
2021
影响因子：
2.8
通讯作者：
Multicenter Clinical Study Group of O
中科院分区：
文献类型：
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作者：
Nakata Ken;Komori Takamichi;Saso Kazuhiro;Ota Hirofumi;Kagawa Yoshinori;Morita Shunji;Noura Shingo;Hayashi Nobuyasu;Uemura Mamoru;Matsuda Chu;Satoh Taroh;Mizushima Tsunekazu;Murata Kohei;Doki Yuichiro;Eguchi Hidetoshi;Multicenter Clinical Study Group of O
目的帕尼单抗化疗预计具有良好的耐受性，并可提高转移性结直肠癌 (mCRC) 患者的生存率。然而，皮肤毒性是其最常见的不良事件。本试验的目的是评估克拉霉素（CAM）预防性抗生素治疗预防帕尼单抗皮肤毒性的有效性和安全性。方法我们对接受帕尼单抗治疗的转移性结直肠癌患者进行了一项 III 期、多中心、开放标签、随机临床试验。符合条件的患者按照 1:1 的比例随机分配到先发制人的抗生素组和对照组。在先发制人组中，在帕尼单抗治疗期间每天继续服用 CAM（200 毫克，每天两次）。对照方案仅包括皮肤护理。主要终点是6周皮肤治疗期间≥2级皮肤毒性的发生率。结果 156名入组患者中，78人接受先发性抗生素治疗，78人接受反应性治疗。在6周皮肤治疗期间，先发性治疗组和对照组中≥2级皮肤毒性的数量和发生率分别为16例（21.3%）和41例（54.7%）（HR，0.32；95% CI，0.17-0.56）。两组其他不良事件发生率几乎没有差异，但先发组 ≥ 3级腹泻发生率较高，为8%，而对照组为1.3%。没有发生与治疗相关的死亡。结论发现预防性口服 CAM 结合相对简单的皮肤护理可有效抑制帕尼单抗引起的 ≥ 2级皮肤毒性的发展。临床试验注册UMIN000011485注册日期2013年9月1日
PurposeChemotherapy with panitumumab is expected to be well tolerated and improve survival in patients with metastatic colorectal cancer (mCRC). However, skin toxicities are its most common adverse events. The aim of this trial was to evaluate the efficacy and safety of pre-emptive antibiotic treatment with clarithromycin (CAM) to prevent panitumumab skin toxicities.MethodsWe conducted a phase lll, multicenter, open-label, randomized clinical trial on mCRC patients treated with panitumumab. Eligible patients were randomly assigned 1:1 to pre-emptive antibiotic and control groups. In the pre-emptive group, CAM administration (200 mg twice per day) continued daily through the panitumumab treatment period. The control regimen consisted of skin care only. The primary end point was the incidence of grade ≥ 2 skin toxicities during the 6-week skin treatment period.ResultsOf 156 enrolled patients, 78 received pre-emptive antibiotic treatment, and 78 received reactive treatment. The number and incidence of grade ≥ 2 skin toxicities during the 6-week skin treatment period were 16 (21.3%) and 41 (54.7%) for the pre-emptive and control groups, respectively (HR, 0.32; 95% CI, 0.17–0.56). There was almost no difference in the rate of other adverse events between the two groups, but the incidence of grade ≥ 3 diarrhea in the pre-emptive group was high, at 8% vs. 1.3% in the control group. There were no treatment-related deaths.ConclusionProphylactic oral CAM together with relatively simple skin care was found to be effective in suppressing the development of grade ≥ 2 skin toxicities induced by panitumumab.Clinical trial registrationUMIN000011485Date of registrationSep 1st, 2013