Fazio N, Biffi R, Maibach R, Hayoz S, Thierstein S, Brauchli P, Bernhard J, Stupp R, Andreoni B, Renne G, Crosta C, Morant R, Chiappa A, Luca F, Zampino M G, Huber O, Goldhirsch A, de Braud F, Roth A D
Unit of Gastrointestinal Medical Oncology and Neuroendocrine Tumors
Division of Gastro-Intestinal Surgery, European Institute of Oncology (IEO), Milan, Italy.
Ann Oncol. 2016 Apr;27(4):668-73. doi: 10.1093/annonc/mdv620. Epub 2015 Dec 27.
Fluorouracil-based adjuvant chemotherapy in gastric cancer has been reported to be effective by several meta-analyses. Perioperative chemotherapy in locally advanced resectable gastric cancer (RGC) has been reported improving survival by two large randomized trials and recent meta-analyses but the role of neoadjuvant chemotherapy and optimal regimen remains to be determined. We compared a neoadjuvant with adjuvant docetaxel-based regimen in a prospective randomized phase III trial, of which we present the 10-year follow-up data.
Patients with cT3-4 anyN M0 or anyT cN1-3 M0 gastric carcinoma, staged with endoscopic ultrasound, computed tomography, bone scan, and laparoscopy, were assigned to receive four 21-day/cycles of docetaxel 75 mg/m(2) day 1, cisplatin 75 mg/m(2) day 1, and fluorouracil 300 mg/m(2)/day over days 1-14, either before (arm A) or after (arm B) gastrectomy. Event-free survival was the primary end point, whereas secondary end points included overall survival, toxicity, down-staging, pathological response, quality of life, and feasibility of adjuvant chemotherapy.
This trial was activated in November 1999 and closed in November 2005 due to insufficient accrual. Of the 70 enrolled patients, 69 were randomized, 34 to arm A and 35 to arm B. No difference in EFS (2.5 years in both arms) or OS (4.3 versus 3.7 years, in arms A and B, respectively) was found. A higher dose intensity of chemotherapy was observed in arm A and more frequent chemotherapy-related serious adverse events occurred in arm B. Surgery was safe after preoperative chemotherapy. A 12% pathological complete response was observed in arm A.
Docetaxel/cisplatin/fluorouracil chemotherapy is promising in preoperative setting of locally advanced RGC. The early stopping could mask the real effectiveness of neoadjuvant treatment. However, the complete pathological tumour responses, feasibility, and safe surgery warrant further investigation of a taxane-based regimen in the preoperative setting.
多项荟萃分析报告称，基于氟尿嘧啶的辅助化疗对胃癌有效。两项大型随机试验及近期的荟萃分析报告称，局部晚期可切除胃癌（RGC）的围手术期化疗可提高生存率，但新辅助化疗的作用及最佳方案仍有待确定。我们在一项前瞻性随机III期试验中比较了新辅助与辅助多西他赛方案，并展示了该试验的10年随访数据。
经内镜超声、计算机断层扫描、骨扫描和腹腔镜分期为cT3 - 4任何N M0或任何T cN1 - 3 M0的胃癌患者，被分配接受4个周期、每21天为一个周期的化疗，具体为第1天多西他赛75mg/m²、第1天顺铂75mg/m²，以及第1 - 14天氟尿嘧啶300mg/m²/天，在胃切除术前（A组）或术后（B组）进行。无事件生存期是主要终点，次要终点包括总生存期、毒性、降期、病理反应、生活质量和辅助化疗的可行性。
该试验于1999年11月启动，由于入组不足于2005年11月结束。70名入组患者中，69名被随机分组，34名进入A组，35名进入B组。未发现无事件生存期（两组均为2.5年）或总生存期（A组为4.3年，B组为3.7年）有差异。A组观察到更高的化疗剂量强度，B组发生更多与化疗相关的严重不良事件。术前化疗后手术安全。A组观察到12%的病理完全缓解。
多西他赛/顺铂/氟尿嘧啶化疗在局部晚期RGC的术前治疗中前景良好。早期停止试验可能掩盖了新辅助治疗的真正有效性。然而，完全的肿瘤病理反应、可行性和安全手术值得在术前进一步研究基于紫杉烷的方案。
