Medical Oncology Department, Institut Mutualiste Montsouris, Paris, France.
Medical Oncology Department, Centre Léon Bérard, Lyon, France.
Eur J Cancer. 2019 Jan;107:46-52. doi: 10.1016/j.ejca.2018.11.006. Epub 2018 Dec 7.
5-Fluorouracil (5-FU) and platinum-based perioperative chemotherapy is standard of care for resectable gastric adenocarcinoma (RGA). Nanoparticle albumin-bound (Nab-) paclitaxel is active in advanced disease but has never been evaluated in the perioperative setting. The objective was to evaluate the efficacy of Nab-paclitaxel in combination with FOLFOX for RGA patients.
We performed a non-randomised, open-label, phase II study. RGA patients were assigned to receive neoadjuvant Nab-paclitaxel (150 mg/m) and FOLFOX q2w for six cycles. Six additional post-operative cycles were kept at the investigator's discretion. The primary end-point was complete pathological response (tumour regression grade [TRG1]) rate. According to Fleming design, 49 patients were required to test H (10% TRG1) and H (25% TRG1). To reject H, TRG1 had to be achieved in 8 patients.
Forty-nine patients were included. Median number of neoadjuvant chemotherapy cycles was 6 (range, 3-6). Median dose intensity for Nab-paclitaxel, oxaliplatin and 5-FU was 96% (38-103%), 97% (47-103%) and 99% (50-112%), respectively. Surgery could not be performed in 5 (10.2%) patients. Tumour resection was R0 for 42 of 44 (95.5%) patients. Pathological review classified tumours as TRG1 to TRG5 for 8 (16.3%), 11 (22.5%), 4 (8.2%), 18 (36.7%) and 3 (6.1%) patients, respectively. Grade 3 or worse toxicities during neoadjuvant chemotherapy were non-febrile neutropenia (20.4%), nausea (8.2%), diarrhoea (8.2%) and neuropathy (6.1%). Of 44 patients, 14 (31.8%) experienced surgery-related complications and three (6.8%) died of surgical complications.
This regimen shows promising activity. Toxicity is manageable but a meaningful rate of surgical complications was observed. This strategy deserves investigation in phase III studies.
5-氟尿嘧啶（5-FU）和铂类为基础的围手术期化疗是可切除胃腺癌（RGA）的标准治疗方法。纳米白蛋白结合紫杉醇（Nab-紫杉醇）在晚期疾病中具有活性，但从未在围手术期进行过评估。本研究旨在评估 Nab-紫杉醇联合 FOLFOX 方案在 RGA 患者中的疗效。
我们进行了一项非随机、开放标签、二期研究。RGA 患者被分配接受新辅助 Nab-紫杉醇（150mg/m）和 FOLFOX 每 2 周治疗 6 个周期。根据研究者的判断，术后还需要接受 6 个周期的辅助化疗。主要终点是完全病理缓解（肿瘤退缩分级[TRG1]）率。根据 Fleming 设计，需要 49 例患者来检验 H（10%TRG1）和 H（25%TRG1）。为了否定 H，TRG1 必须在 8 例患者中实现。
共纳入 49 例患者。新辅助化疗周期中位数为 6 个（范围 3-6 个）。Nab-紫杉醇、奥沙利铂和 5-FU 的中位剂量强度分别为 96%（38-103%）、97%（47-103%）和 99%（50-112%）。5 例（10.2%）患者因各种原因无法手术。44 例患者中有 42 例（95.5%）肿瘤切除为 R0。病理复查显示肿瘤分别为 TRG1 至 TRG5 的患者有 8 例（16.3%）、11 例（22.5%）、4 例（8.2%）、18 例（36.7%）和 3 例（6.1%）。新辅助化疗期间发生 3 级或更高级别的毒性反应有非发热性中性粒细胞减少（20.4%）、恶心（8.2%）、腹泻（8.2%）和周围神经病变（6.1%）。44 例患者中，14 例（31.8%）发生手术相关并发症，3 例（6.8%）死于手术并发症。
该方案显示出良好的疗效。毒性可管理，但观察到相当比例的手术并发症。这种策略值得在 III 期研究中进一步探讨。
