巴克斯：局部晚期直肠癌（LARC）患者新辅助化疗（NACT）的一项随机非对照II期研究。

BACCHUS: A randomised non-comparative phase II study of neoadjuvant chemotherapy (NACT) in patients with locally advanced rectal cancer (LARC).

作者信息

Glynne-Jones R, Hall M R, Lopes A, Pearce S, Goh V, Bosompem S, Bridgewater J, Chau I, Wasan H, Moran B, Melcher L, West N P, Quirke P, Wong W-L, Beare S, Hava N, Duggan M, Harrison M

机构信息

Radiotherapy Department, Mount Vernon Centre for Cancer Treatment, Mount Vernon Hospital, Northwood, UK.

Cancer Research UK & University College London Cancer Trials Centre, London, UK.

出版信息

Heliyon. 2018 Sep 22;4(9):e00804. doi: 10.1016/j.heliyon.2018.e00804. eCollection 2018 Sep.

BACKGROUND

Chemoradiation (CRT) or short-course radiotherapy (SCRT) are standard treatments for locally advanced rectal cancer (LARC). We evaluated the efficacy/safety of two neoadjuvant chemotherapy (NACT) regimens as an alternative prior to total mesorectal excision (TME).

METHODS/DESIGN: This multi-centre, phase II trial in patients with magnetic resonance imaging (MRI) defined high-risk LARC (>cT3b, cN2+ or extramural venous invasion) randomised patients (1:1) to FOLFOX + Bevacizumab (Arm 1) or FOLFOXIRI + bevacizumab (Arm 2) every 14 days for 6 cycles prior to surgery. Patients were withdrawn if positron emission tomography (PET) standardised uptake value (SUV) after 3 cycles failed to decrease by >30% or increased compared to baseline. Primary endpoint was pathological complete response rate (pCR). Secondary endpoints included adverse events (AE) and toxicity. Neoadjuvant rectal (NAR) scores based on "T" and "N" downstaging were calculated.

FINDINGS

Twenty patients aged 18-75 years were randomised. The trial stopped early because of poor accrual. Seventeen patients completed all 6 cycles of NACT. One stopped due to myocardial infarction, 1 poor response on PET (both received CRT) and 1 committed suicide. 11 patients had G3 AE, 1 G4 AE (neutropenia), and 1 G5 (suicide). pCR (the primary endpoint) was 0/10 for Arm 1 and 2/10 for Arm 2 i.e. 2/20 (10%) overall. Median NAR score was 14·9 with 5 (28%), 7 (39%), and 6 (33%) having low, intermediate, or high scores. Surgical morbidity was acceptable (1/18 wound infection, no anastomotic leak/pelvic sepsis/fistulae). The 24-month progression-free survival rate was 75% (95% CI: 60%-85%).

INTERPRETATION

The primary endpoint (pCR rate) was not met. However, FOLFOXIRI and bevacizumab achieved promising pCR rates, low NAR scores and was well-tolerated. This regimen is suitable for testing as the novel arm against current standards of SCRT and/or CRT in a future trial.

背景

放化疗（CRT）或短程放疗（SCRT）是局部晚期直肠癌（LARC）的标准治疗方法。我们评估了两种新辅助化疗（NACT）方案作为全直肠系膜切除术（TME）前替代方案的疗效/安全性。

方法/设计：这项针对磁共振成像（MRI）定义的高危LARC（>cT3b、cN2+或壁外静脉侵犯）患者的多中心II期试验，将患者按1:1随机分为两组，在手术前每14天接受FOLFOX + 贝伐单抗（第1组）或FOLFOXIRI + 贝伐单抗（第2组）治疗，共6个周期。如果3个周期后正电子发射断层扫描（PET）标准化摄取值（SUV）未能较基线下降>30%或升高，则将患者排除。主要终点是病理完全缓解率（pCR）。次要终点包括不良事件（AE）和毒性。计算基于 “T” 和 “N” 降期的新辅助直肠（NAR）评分。

结果

20名年龄在18 - 75岁的患者被随机分组。由于入组情况不佳，试验提前终止。17名患者完成了所有6个周期的NACT。1名因心肌梗死停止治疗，1名PET反应不佳（两者均接受了CRT），1名自杀。11名患者发生3级AE，1名发生4级AE（中性粒细胞减少），1名发生5级（自杀）。主要终点pCR率在第1组为0/10，在第2组为2/10，即总体为2/20（10%）。NAR评分中位数为14·9，其中5名（28%）、7名（39%）和6名（33%）分别为低、中、高分。手术并发症可接受（1/18伤口感染，无吻合口漏/盆腔脓毒症/瘘管）。24个月无进展生存率为75%（95%CI：60% - 85%）。