Division of Hematology/Oncology, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston.
Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston.
JAMA Oncol. 2018 Jul 1;4(7):963-969. doi: 10.1001/jamaoncol.2018.0329.
Patients with borderline-resectable pancreatic ductal adenocarcinoma have historically poor outcomes with surgery followed by adjuvant chemotherapy. Evaluation of a total neoadjuvant approach with highly active therapy is warranted.
To evaluate the margin-negative (R0) resection rate in borderline-resectable pancreatic ductal adenocarcinoma after neoadjuvant FOLFIRINOX (fluorouracil, irinotecan, and oxaliplatin) therapy and individualized chemoradiotherapy.
DESIGN, SETTING, AND PARTICIPANTS: A single-arm, phase 2 clinical trial was conducted at a large academic hospital with expertise in pancreatic surgery from August 3, 2012, through August 31, 2016, among 48 patients with newly diagnosed, previously untreated, localized pancreatic cancer determined to be borderline resectable by multidisciplinary review, who had Eastern Cooperative Oncology Group performance status 0 or 1 and adequate hematologic, renal, and hepatic function. Median follow-up for the analysis was 18.0 months among the 30 patients still alive at study completion.
Patients received FOLFIRINOX for 8 cycles. Upon restaging, patients with resolution of vascular involvement received short-course chemoradiotherapy (5 Gy × 5 with protons) with capecitabine. Patients with persistent vascular involvement received long-course chemoradiotherapy with fluorouracil or capecitabine.
The primary outcome was R0 resection rate; secondary outcomes were median progression-free survival (PFS) and median overall survival (OS).
Of the 48 eligible patients, 27 were men and 21 were women, with a median age of 62 years (range, 46-74 years). Of the 43 patients who planned to receive 8 preoperative cycles of chemotherapy, 34 (79%) were able to complete all cycles. Twenty-seven patients (56%) had short-course chemoradiotherapy, while 17 patients (35%) had long-course chemoradiotherapy. R0 resection was achieved in 31 of the 48 eligible patients (65%; 95% CI, 49%-78%). Among the 32 patients who underwent resection, the R0 resection rate was 97% (n = 31). Median PFS among all eligible patients was 14.7 months (95% CI, 10.5 to not reached), with 2-year PFS of 43%; median OS was 37.7 months (95% CI, 19.4 to not reached), with 2-year OS of 56%. Among patients who underwent resection, median PFS was 48.6 months (95% CI, 14.4 to not reached) and median OS has not been reached, with a 2-year PFS of 55% and a 2-year OS of 72%.
Preoperative FOLFIRINOX followed by individualized chemoradiotherapy in borderline resectable pancreatic cancer results in high rates of R0 resection and prolonged median PFS and median OS, supporting ongoing phase 3 trials.
ClinicalTrials.gov Identifier: NCT01591733.
历史上，对于接受手术联合辅助化疗的边界可切除胰腺导管腺癌患者，其预后较差。因此，需要评估采用高度活跃疗法的新辅助全治疗方案。
评估新辅助 FOLFIRINOX（氟尿嘧啶、伊立替康和奥沙利铂）治疗联合个体化放化疗后，边界可切除胰腺导管腺癌患者的阴性切缘（R0）切除率。
设计、环境和参与者：这是一项在一家具有胰腺外科专业知识的大型学术医院进行的单臂、2 期临床试验，从 2012 年 8 月 3 日至 2016 年 8 月 31 日，共有 48 名新诊断的、未经治疗的局部胰腺癌患者参与，这些患者经多学科评估确定为边界可切除，东部合作肿瘤学组（ECOG）体能状态为 0 或 1，且血液学、肾脏和肝功能足够。在研究完成时仍存活的 30 名患者中，中位随访时间为 18.0 个月。
患者接受 FOLFIRINOX 治疗 8 个周期。重新分期后，血管受累缓解的患者接受短程放化疗（质子 5 Gy×5）联合卡培他滨。血管受累持续存在的患者接受氟尿嘧啶或卡培他滨长程放化疗。
主要结局是 R0 切除率；次要结局是中位无进展生存期（PFS）和中位总生存期（OS）。
48 名符合条件的患者中，27 名男性，21 名女性，中位年龄 62 岁（范围 46-74 岁）。43 名计划接受 8 个术前周期化疗的患者中，34 名（79%）能够完成所有周期。27 名患者（56%）接受短程放化疗，17 名患者（35%）接受长程放化疗。48 名符合条件的患者中，有 31 名（65%；95%CI，49%-78%）达到阴性切缘（R0 切除）。在接受手术的 32 名患者中，R0 切除率为 97%（n=31）。所有符合条件的患者中位 PFS 为 14.7 个月（95%CI，10.5-未达到），2 年 PFS 为 43%；中位 OS 为 37.7 个月（95%CI，19.4-未达到），2 年 OS 为 56%。在接受手术的患者中，中位 PFS 为 48.6 个月（95%CI，14.4-未达到），中位 OS 尚未达到，2 年 PFS 为 55%，2 年 OS 为 72%。
在边界可切除的胰腺癌中，术前 FOLFIRINOX 联合个体化放化疗可获得较高的 R0 切除率和延长的中位 PFS 和中位 OS，支持正在进行的 3 期临床试验。
ClinicalTrials.gov 标识符：NCT01591733。
