Total Neoadjuvant Therapy With FOLFIRINOX in Combination With Losartan Followed by Chemoradiotherapy for Locally Advanced Pancreatic Cancer A Phase 2 Clinical Trial
Total Neoadjuvant Therapy With FOLFIRINOX in Combination With Losartan Followed by Chemoradiotherapy for Locally Advanced Pancreatic Cancer A Phase 2 Clinical Trial
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DOI：
10.1001/jamaoncol.2019.0892
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发表时间：
2019-07-01
期刊：
影响因子：
28.4
通讯作者：
Hong, Theodore S.
中科院分区：
文献类型：
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作者：
Murphy, Janet E.;Wo, Jennifer Y.;Hong, Theodore S.
局部晚期胰腺癌患者历来预后不良。评估完全新辅助方法是有必要的。目的评价新辅助FOLFIRINOX（氟尿嘧啶、亚叶酸钙、奥沙利铂和伊立替康）和氯沙坦联合放化疗治疗局部晚期胰腺癌的边缘阴性（R0）切除率。设计、环境和参与者：2013年8月22日至2018年5月22日，在一家大型学术医院进行了一项单臂2期临床试验，纳入了49例未经治疗的局部晚期不可切除胰腺癌患者，经多学科评价确定。患者在东方肿瘤合作组的表现为0或1，血液学、肾功能和肝功能正常。在27例研究完成时仍然存活的患者中，分析的中位随访时间为17.1个月（范围5.0-53.7）。干预措施患者接受FOLFIRINOX和氯沙坦治疗8个周期。化疗后放射学可切除的肿瘤患者接受卡培他滨短程放化疗（5 GyE x 5质子）。持续血管受累的患者接受氟尿嘧啶或卡培他滨的长期放化疗（50.4 Gy，血管增强至58.8 Gy）。主要结果及测量指标：R0切除率。结果在49例患者中（女性26例，男性23例，中位年龄63岁[42-78岁]），39例患者完成了8个周期的FOLFIRINOX和氯沙坦治疗；10例患者由于进展（5例）、氯沙坦不耐受（3例）和毒性（2例）而少于8个周期。7例（16%）患者接受短期放化疗，38例（84%）患者接受长期放化疗。42例（86%）患者接受了手术尝试，49例患者中有34例（69%;95% CI, 55%-82%）实现了R0切除。总体中位无进展生存期为17.5个月（95% CI: 13.9-22.7），中位总生存期为31.4个月（95% CI, 18.1-38.5）。在接受切除术的患者中，中位无进展生存期为21.3个月（95% CI, 16.6-28.2），中位总生存期为33.0个月（95% CI， 31.4至未达到）。结论和相关性：FOLFIRINOX、氯沙坦和放化疗的全面新辅助治疗可以降低局部晚期胰管腺癌的分期，R0切除率为61%。
IMPORTANCE Patients with locally advanced pancreatic cancer have historically poor outcomes. Evaluation of a total neoadjuvant approach is warranted.OBJECTIVE To evaluate the margin-negative (R0) resection rate of neoadjuvant FOLFIRINOX (fluorouracil, leucovorin, oxaliplatin, and irinotecan) and losartan followed by chemoradiotherapy for locally advanced pancreatic cancer.DESIGN, SETTING, AND PARTICIPANTS A single-arm phase 2 clinical trial was conducted at a large academic hospital from August 22, 2013, to May 22, 2018, among 49 patients with previously untreated locally advanced unresectable pancreatic cancer as determined by multidisciplinary review. Patients had Eastern Cooperative Oncology Group performance status 0 or 1 and adequate hematologic, renal, and hepatic function. Median follow-up for the analysis was 17.1 months (range, 5.0-53.7) among 27 patients still alive at study completion.INTERVENTIONS Patients received FOLFIRINOX and losartan for 8 cycles. Patients with radiographically resectable tumor after chemotherapy received short-course chemoradiotherapy (5 GyE x 5 with protons) with capecitabine. Patients with persistent vascular involvement received long-course chemoradiotherapy (50.4 Gy with a vascular boost to 58.8 Gy) with fluorouracil or capecitabine.MAIN OUTCOMES AND MEASURES R0 resection rate.RESULTS Of the 49 patients (26 women and 23 men; median age 63 years [range, 42-78 years]), 39 completed 8 cycles of FOLFIRINOX and losartan; 10 patients had fewer than 8 cycles due to progression (5 patients), losartan intolerance (3 patients), and toxicity (2 patients). Seven patients (16%) had short-course chemoradiotherapy while 38 (84%) had long-course chemoradiotherapy. Forty-two (86%) patients underwent attempted surgery, with R0 resection achieved in 34 of 49 patients (69%; 95% CI, 55%-82%). Overall median progression-free survival was 17.5 months (95% CI: 13.9-22.7) and median overall survival was 31.4 months (95% CI, 18.1-38.5). Among patients who underwent resection, median progression-free survival was 21.3 months (95% CI, 16.6-28.2), and median overall survival was 33.0 months (95% CI, 31.4 to not reached).CONCLUSIONS AND RELEVANCE Total neoadjuvant therapy with FOLFIRINOX, losartan, and chemoradiotherapy provides downstaging of locally advanced pancreatic ductal adenocarcinoma and is associated with an R0 resection rate of 61%.