Medical Oncology Department, Hospital Clínic, Translational Genomics and Targeted Therapeutics in Solid Tumors Group, IDIBAPS, University of Barcelona, Barcelona, Spain.
Surgical Department, Hospital Clínic Barcelona, IDIBAPS, University of Barcelona, Barcelona, Spain.
Cancer Chemother Pharmacol. 2018 Dec;82(6):935-943. doi: 10.1007/s00280-018-3682-9. Epub 2018 Sep 17.
Neoadjuvant therapy (NAT) for pancreatic adenocarcinoma (PDAC) patients has shown promising results in non-randomized trials. This is a multi-institutional phase II trial of NAT in resectable PDAC patients.
Patients with confirmed resectable PDAC after agreement by two expert radiologists were eligible. Patients received three cycles of GEM (1000 mg/m/week) plus daily erlotinib (ERL) (100 mg/day). After re-staging, patients without progressive disease underwent 5 weeks of therapy with GEM (300 mg/m/week), ERL 100 mg/day and concomitant radiotherapy (45 Gy). Efficacy was assessed using tumor regression grade (TRG) and resection margin status. Using a single-arm Simon's design, considering the therapy not useful if R0 < 40% and useful if the R0 > 70% (alpha 5%, beta 10%), 24 patients needed to be recruited. This trial was registered at ClinicalTrials.gov, number NCT01389440.
Twenty-five patients were enrolled. Adverse effects of NAT were mainly mild gastrointestinal disorders. Resectability rate was 76%, with a R0 rate of 63.1% among the resected patients. Median overall survival (OS) and disease-free survival (DFS) were 23.8 (95% CI 11.4-36.2) and 12.8 months (95% CI 8.6-17.1), respectively. R0 resection patients had better median OS, compared with patients with R1 resection or not resected (65.5 months vs. 15.5 months, p = 0.01). N0 rate among the resected patients was 63.1%, and showed a longer median OS (65.5 vs. 15.2 months, p = 0.009).
The results of this study confirm promising oncologic results with NAT for patients with resectable PDAC. Therefore, the present trial supports the development of phase II randomized trials comparing NAT vs. upfront surgery in resectable pancreatic cancer.
新辅助治疗（NAT）在胰腺导管腺癌（PDAC）患者中的非随机试验中显示出了有前景的结果。这是一项针对可切除 PDAC 患者的多机构 II 期 NAT 试验。
经过两位专家放射科医生的确认，符合可切除 PDAC 标准的患者有资格参加。患者接受三个周期的 GEM（1000mg/m/周）加每天厄洛替尼（ERL）（100mg/天）治疗。重新分期后，无疾病进展的患者接受 5 周的 GEM（300mg/m/周）、ERL 100mg/天和同步放疗（45Gy）治疗。使用肿瘤消退分级（TRG）和切缘状态评估疗效。采用 Simon 单臂设计，考虑到 R0<40%时治疗无效，R0>70%时治疗有效（α5%，β10%），需要招募 24 名患者。该试验在 ClinicalTrials.gov 注册，编号为 NCT01389440。
共纳入 25 名患者。NAT 的不良反应主要为轻度胃肠道紊乱。可切除率为 76%，其中切除患者的 R0 率为 63.1%。中位总生存期（OS）和无病生存期（DFS）分别为 23.8 个月（95%CI 11.4-36.2）和 12.8 个月（95%CI 8.6-17.1）。与 R1 切除或未切除的患者相比，R0 切除患者的中位 OS 更好（65.5 个月 vs. 15.5 个月，p=0.01）。切除患者的 N0 率为 63.1%，中位 OS 更长（65.5 个月 vs. 15.2 个月，p=0.009）。
本研究结果证实了新辅助治疗在可切除 PDAC 患者中的有前景的肿瘤学结果。因此，本试验支持开展比较新辅助治疗与可切除胰腺癌直接手术的 II 期随机试验。
