Unit of Medical Oncology 2, Azienda Ospedaliero-Universitaria Pisana, Via Roma, 56126 Pisa, Italy; Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Via Roma, 56126 Pisa, Italy.
Unit of Medical Oncology 2, Azienda Ospedaliero-Universitaria Pisana, Via Roma, 56126 Pisa, Italy.
Eur J Cancer. 2019 Mar;110:32-41. doi: 10.1016/j.ejca.2019.01.006. Epub 2019 Feb 7.
Neoadjuvant chemoradiotherapy (CRT) in locally advanced rectal cancer (LARC) does not achieve effective control of distant metastases. Induction chemotherapy is a promising strategy, and bevacizumab (BV) could improve the results of CRT. 5-Fluorouracil, oxaliplatin and irinotecan (FOLFOXIRI) plus BV is a treatment option in metastatic colorectal cancer. We evaluate feasibility and efficacy of neoadjuvant treatment comprising induction FOLFOXIRI plus BV followed by CRT with fluoropyrimidines plus BV.
In this phase II single-arm trial, patients node-positive or clinical T4 or high-risk T3 LARC underwent 6 cycles of induction FOLFOXIRI plus BV, followed by CRT (50.4 Gy plus concomitant capecitabine) and BV (5 mg/kg on days 1, 15 and 28). Surgery was planned 8 weeks after completion of CRT. Primary end-point was 2-year disease-free survival (DFS).
We enrolled 49 patients: All but one (withdrewing consent after enrolment) were included in the per-protocol analyses. The study met its primary end-point: 36 patients were free of recurrence at 2 years (2-y DFS: 80.45%, 95% confidence interval [CI]: 78.79-82.10). Forty-four patients underwent surgery; pathologic complete response rate was 36.4%. Forty-six patients completed induction: neutropenia (41.6%) and diarrhoea (12.5%) were main G3/4 toxicities. Forty-five patients received CRT, but the protocol was amended and the capecitabine schedule during CRT was slightly modified after 13 patients due to the incidence of G3 hand-foot syndrome and proctitis (23.1%). After amendment, no severe events during CRT were reported.
FOLFOXIRI plus BV followed by CRT plus BV is feasible and active. Results in terms of DFS suggest that this strategy may improve distant disease control in LARC.
局部晚期直肠癌（LARC）的新辅助放化疗（CRT）无法有效控制远处转移。诱导化疗是一种很有前途的策略，贝伐珠单抗（BV）可以改善 CRT 的结果。5-氟尿嘧啶、奥沙利铂和伊立替康（FOLFOXIRI）加 BV 是转移性结直肠癌的一种治疗选择。我们评估了包含诱导 FOLFOXIRI 加 BV 后再进行 CRT 加氟嘧啶加 BV 的新辅助治疗方案的可行性和疗效。
在这项 II 期单臂试验中，淋巴结阳性或临床 T4 或高危 T3 LARC 患者接受 6 个周期的诱导 FOLFOXIRI 加 BV，然后进行 CRT（50.4Gy 加同期卡培他滨）和 BV（第 1、15 和 28 天 5mg/kg）。CRT 完成后 8 周计划进行手术。主要终点是 2 年无病生存率（DFS）。
我们共纳入 49 例患者：除 1 例（入组后撤回同意）外，所有患者均纳入方案分析。该研究达到了主要终点：36 例患者在 2 年内无复发（2 年 DFS：80.45%，95%置信区间[CI]：78.79-82.10）。44 例患者接受了手术；病理完全缓解率为 36.4%。46 例患者完成了诱导治疗：中性粒细胞减少症（41.6%）和腹泻（12.5%）是主要的 3/4 级毒性。45 例患者接受了 CRT，但由于 13 例患者发生 3 级手足综合征和直肠炎（23.1%），方案修订并略修改了 CRT 期间的卡培他滨方案。修订后，CRT 期间未报告严重事件。
FOLFOXIRI 加 BV 序贯 CRT 加 BV 是可行且有效的。DFS 结果表明，这种策略可能会改善 LARC 的远处疾病控制。
