Department of General and Abdominal Surgery, University Hospital of Mainz, Langenbeck-strasse 1, 55118 Mainz, Germany.
BMC Cancer. 2011 Aug 10;11:346. doi: 10.1186/1471-2407-11-346.
Despite major improvements in the perioperative outcome of pancreas surgery, the prognosis of pancreatic cancer after curative resection remains poor. Adjuvant chemotherapy increases disease-free and overall survival, but this treatment cannot be offered to a significant proportion of patients due to the surgical morbidity. In contrast, almost all patients can receive (neo)adjuvant chemotherapy before surgery. This treatment is safe and effective, and has resulted in a median survival of 26.5 months in a recent phase II trial. Moreover, neoadjuvant chemotherapy improves the nutritional status of patients with pancreatic cancer. This multicenter phase III trial (NEOPAC) has been designed to explore the efficacy of neoadjuvant chemotherapy.
METHODS/DESIGN: This is a prospective randomized phase III trial. Patients with resectable cytologically proven adenocarcinoma of the pancreatic head are eligible for this study. All patients must be at least 18 years old and must provide written informed consent. An infiltration of the superior mesenteric vein > 180° or major visceral arteries are considered exclusion criteria. Eligible patients will be randomized to surgery followed by adjuvant gemcitabine (1000 mg/m(2)) for 6 months or neoadjuvant chemotherapy (gemcitabine 1000 mg/m(2), oxaliplatin 100 mg/m(2)) followed by surgery and the same adjuvant treatment. Neoadjuvant chemotherapy is given four times every two weeks. The staging as well as the restaging protocol after neoadjuvant chemotherapy include computed tomography of chest and abdomen and diagnostic laparoscopy. The primary study endpoint is progression-free survival. According to the sample size calculation, 155 patients need to be randomized to each treatment arm. Disease recurrence will be documented by scheduled computed tomography scans 9, 12, 15, 21 and thereafter every 6 months until disease progression. For quality control, circumferential resection margins are marked intraoperatively, and representative histological sections will be centrally reviewed by a dedicated pathologist.
The NEOPAC study will determine the efficacy of neoadjuvant chemotherapy in pancreatic cancer for the first time and offers a unique potential for translational research. Furthermore, this trial will provide the unbiased overall survival of all patients undergoing surgery for resectable cancer of the pancreatic head.
clinicalTrials.gov NCT01314027.
尽管胰腺手术围手术期结果有了重大改善，但胰腺癌根治性切除术后的预后仍然较差。辅助化疗可提高无病生存率和总生存率，但由于手术发病率，相当一部分患者无法接受这种治疗。相比之下，几乎所有患者都可以在术前接受（新）辅助化疗。这种治疗安全有效，最近的一项 II 期试验中位生存期达到 26.5 个月。此外，新辅助化疗可改善胰腺癌患者的营养状况。这项多中心 III 期试验（NEOPAC）旨在探讨新辅助化疗的疗效。
方法/设计：这是一项前瞻性随机 III 期试验。可切除的经细胞学证实的胰头腺癌患者有资格参加本研究。所有患者必须年满 18 岁，并提供书面知情同意书。肠系膜上静脉浸润>180°或主要内脏动脉视为排除标准。符合条件的患者将随机分为手术组和术后辅助吉西他滨（1000mg/m²）治疗 6 个月，或新辅助化疗组（吉西他滨 1000mg/m²，奥沙利铂 100mg/m²）后手术和相同的辅助治疗。新辅助化疗每 2 周给药 4 次。新辅助化疗后的分期和再分期方案包括胸部和腹部 CT 扫描以及诊断性腹腔镜检查。主要研究终点是无进展生存期。根据样本量计算，每组需要随机分配 155 例患者。通过定期 CT 扫描记录疾病复发情况，分别在第 9、12、15、21 天以及此后每 6 个月直至疾病进展。为了质量控制，在手术中标记环周切缘，由专门的病理学家对代表性的组织切片进行中心审查。
NEOPAC 研究将首次确定新辅助化疗在胰腺癌中的疗效，并为转化研究提供独特的潜力。此外，该试验将为所有接受可切除胰头癌手术的患者提供无偏倚的总生存率。
clinicalTrials.gov NCT01314027。
