Multicenter phaseⅡ clinical study of the efficiency and safety of capecitabine plus intermittent oxaliplatin with bevacizumab as first-line therapy in patients with metastatic colorectal cancer(VOICE trial)
Multicenter phaseⅡ clinical study of the efficiency and safety of capecitabine plus intermittent oxaliplatin with bevacizumab as first-line therapy in patients with metastatic colorectal cancer(VOICE trial)
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卡培他滨联合间歇性奥沙利铂联合贝伐珠单抗一线治疗转移性结直肠癌的有效性和安全性的多中心Ⅱ期临床研究（VOICE试验）
DOI：
10.1007/s00384-021-03995-7
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发表时间：
2021
期刊：
影响因子：
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通讯作者：
Matsubara H.
中科院分区：
文献类型：
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作者：
Kosugi C;Koda K;Denda T;Ishibashi K;Ishida H;Seike K;Sakata H;Yanagisawa S;Miyazaki A;Takayama W;Koike N;Shimizu H;Matsubara H.
目的本 II 期研究的目的是评估转移性结直肠癌 (mCRC) 中五周期 CAPOX（卡培他滨加奥沙利铂）加贝伐单抗联合治疗，随后卡培他滨加贝伐单抗五周期维持治疗以及重新引入 CAPOX 加贝伐单抗五个周期的疗效和安全性，并采用预先计划的间歇性奥沙利铂策略治疗转移性结直肠癌 (mCRC)。 方法对未经治疗的 mCRC 患者进行治疗CAPOX（第 1 天 130 mg/m2 奥沙利铂，第 1-14 天 2000 mg/m2/天卡培他滨，每 21 天）每 3 周 + 贝伐单抗 (7.5 mg/kg)，持续 5 个周期，不使用奥沙利铂的维持治疗，持续 5 个周期，以及 CAPOX + 贝伐单抗重新引入，持续 5 个周期或当肿瘤进展时。主要终点为无进展生存期（PFS），次要终点为治疗失败时间（TTF）、总生存期、有效率（RR）和安全性。 结果符合纳入标准的 47 例患者纳入疗效和安全性评价。中位 PFS 为 14.1 个月（95% 置信区间 [CI]，8.6–19.5），中位 TTF 为 12.3 个月（95% CI，10.3–14.3）。诱导治疗期间的客观 RR 为 51.1% (24/47)，维持治疗期间为 58.3% (21/36)，重新引入治疗期间为 63.6% (14/22)。中性粒细胞减少、腹泻、周围感觉神经病变、静脉血栓栓塞或 ≥ 3级过敏反应的患者发生率为2.1%。 结论 CAPOX加贝伐单抗治疗采用预先计划的间歇性奥沙利铂策略，包括简短的五个周期诱导治疗、卡培他滨加贝伐单抗的五个周期维持治疗和CAPOX加贝伐单抗组成的五周期再引入治疗是安全有效的适用于 mCRC 患者。试验注册UMIN ID：000,005,732，注册日期：2011 年 6 月 7 日。 https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000006695
PurposeThe aim of this phase II study was to evaluate the efficacy and safety of combination therapy with five-cycle CAPOX (capecitabine plus oxaliplatin) plus bevacizumab, followed by five-cycle maintenance therapy with capecitabine plus bevacizumab and reintroduction of CAPOX plus bevacizumab for five cycles, with a preplanned intermittent oxaliplatin strategy in metastatic colorectal cancer (mCRC).MethodsPatients with untreated mCRC were administered CAPOX (130 mg/m2oxaliplatin on day 1, 2000 mg/m2/day capecitabine on days 1–14, every 21 days) + bevacizumab (7.5 mg/kg) every 3 weeks for five cycles, maintenance treatment without oxaliplatin for five cycles, and CAPOX + bevacizumab reintroduction for five cycles or upon tumor progression. The primary endpoint was progression-free survival (PFS), and the secondary endpoints were the time to treatment failure (TTF), overall survival, response rate (RR), and safety.ResultsForty-seven patients who fulfilled the inclusion criteria were enrolled in the evaluation of efficacy and safety. Median PFS was 14.1 months (95% confidence interval [CI], 8.6–19.5), and median TTF was 12.3 months (95% CI, 10.3–14.3). The objective RRs were 51.1% (24/47) during induction therapy, 58.3% (21/36) during maintenance therapy, and 63.6% (14/22) during reintroduction therapy. The frequency of patients with neutropenia, diarrhea, peripheral sensory neuropathy, venous thromboembolism, or grade ≥ 3 allergic reactions was 2.1%.ConclusionCAPOX plus bevacizumab therapy with a preplanned intermittent oxaliplatin strategy consisting of brief five-cycle induction therapy, five-cycle maintenance therapy with capecitabine plus bevacizumab, and five-cycle reintroduction therapy consisting of CAPOX plus bevacizumab is safe and effective for mCRC patients.Trial registrationUMIN ID: 000,005,732, date of registration: June 7, 2011. https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000006695