Neoadjuvant plus adjuvant or only adjuvant nab-paclitaxel plus gemcitabine for resectable pancreatic cancer - the NEONAX trial (AIO-PAK-0313), a prospective, randomized, controlled, phase II study of the AIO pancreatic cancer group

被引：57

作者：

Ettrich, Thomas J. ^{[1
]}

Berger, Andreas W. ^{[1
]}

Perkhofer, Lukas ^{[1
]}

Daum, Severin ^{[2
]}

Koenig, Alexander ^{[3
]}

Dickhut, Andreas ^{[4
]}

Wittel, Uwe ^{[5
]}

Wille, Kai ^{[6
]}

Geissler, Michael ^{[7
]}

Alguel, Hana ^{[8
]}

Gallmeier, Eike ^{[9
]}

Atzpodien, Jens ^{[10
]}

Kornmann, Marko ^{[11
]}

Muche, Rainer ^{[12
]}

Prasnikar, Nicole ^{[13
]}

Tannapfel, Andrea ^{[14
]}

Reinacher-Schick, Anke ^{[15
]}

Uhl, Waldemar ^{[16
]}

Seufferlein, Thomas ^{[1
]}

机构：

[1] Univ Ulm, Dept Internal Med 1, Albert Einstein Allee 23, D-89081 Ulm, Germany

[2] Charite Univ Med Berlin, Dept Gastroenterol Infect Dis & Rheumatol, Hindenburgdamm 30, D-12200 Berlin, Germany

[3] Univ Med Ctr Goettingen, Dept Gastroenterol & Gastrointestinal Oncol, Robert Koch Str 40, D-37075 Gottingen, Germany

[4] Fulda Hosp, Dept Oncol Hematol, Pacelliallee 4, D-36043 Fulda, Germany

[5] Univ Freiburg, Dept Gen & Visceral Surg, Hugstetter Str 55, D-79106 Freiburg, Germany

[6] Johannes Wesling Klinikum Minden, Dept Hematol & Med Oncol, Hans Nolte Str 1, D-32429 Minden, Germany

[7] Esslingen Hosp, Dept Internal Med, Oncol Hematol, Gastroenterol, Hirschlandstr 97, D-73730 Esslingen, Esslingen, Germany

[8] Tech Univ Munich, Dept Internal Med 2, Ismaninger Str 22, D-81675 Munich, Germany

[9] Univ Marburg, Dept Gastroenterol & Endocrinol, Baldingerstr, D-35043 Marburg, Germany

[10] Niels Stensen Kliniken, Dept Med Oncol & Hematol, Alte Rothenfelder Str 23, D-49124 Georgsmarienhutte, Germany

[11] Univ Ulm, Dept Gen & Visceral Surg, Albert Einstein Allee 23, D-89081 Ulm, Germany

[12] Univ Ulm, Inst Epidemiol & Med Biometry, Schwabstr 13, D-89081 Ulm, Germany

[13] Asklepios Klin Barmbek, Dept Oncol, Rubenkamp 220, D-22291 Hamburg, Germany

[14] Ruhr Univ Bochum, Dept Pathol, Burkle de la Camp Pl 1, D-44789 Bochum, Germany

[15] Ruhr Univ Bochum, Dept Internal Med, Gudrunstr 56, D-44791 Bochum, Germany

[16] Ruhr Univ Bochum, Dept Surg, Gudrunstr 56, D-44791 Bochum, Germany

来源：

BMC CANCER | 2018年 / 18卷

关键词：

Pancreatic ductal adenocarcinoma; Pancreatic cancer; Resectable; Neoadjuvant chemotherapy; Perioperative chemotherapy; HOSPITAL ANXIETY; CHEMORADIOTHERAPY; CHEMOTHERAPY; RESECTION; SURVIVAL; THERAPY; METAANALYSIS; CARCINOMA; SURGERY; QLQ-C30;

D O I：

10.1186/s12885-018-5183-y

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

BackgroundEven clearly resectable pancreatic cancer still has an unfavorable prognosis. Neoadjuvant or perioperative therapies might improve the prognosis of these patients. Thus, evaluation of perioperative chemotherapy in resectable pancreatic cancer in a prospective, randomized trial is warranted. A substantial improvement in overall survival of patients with metastatic pancreatic cancer with FOLFIRINOX and nab-paclitaxel/gemcitabine vs standard gemcitabine has been demonstrated in phase III-trials. Indeed nab-paclitaxel/gemcitabine has a more favorable toxicity profile compared to the FOLFIRINOX protocol and appears applicable in a perioperative setting.MethodsNEONAX is an interventional, prospective, randomized, controlled, open label, two sided phase II study with an unconnected analysis of the results in both experimental arms against a fixed survival probability (38% at 18months with adjuvant gemcitabine), NCT02047513. NEONAX will enroll 166 patients with resectable pancreatic ductal adenocarcinoma ( cT3, N0 or N1, cM0) in two arms: Arm A (perioperative arm): 2cycles nab-paclitaxel (125mg/m2)/gemcitabine (1000mg/m2, d1, 8 and 15 of an 28day-cycle) followed by tumor surgery followed by 4cycles nab-paclitaxel/gemcitabine, Arm B (adjuvant arm): tumor surgery followed by 6cycles nab-paclitaxel/gemcitabine. The randomization (1:1) is eminent to avoid allocation bias between the groups. Randomization is stratified for tumor stage (ct1/2 vs. cT3) and lymph node status (cN0 vs. cN1). Primary objective is disease free survival (DFS) at 18months after randomization. Key secondary objectives are 3-year overall survival (OS) rate and DFS rate, progression during neoadjuvant therapy, R0 and R1 resection rate, quality of life and correlation of DFS, OS and tumor regression with pharmacogenomic markers, tumor biomarkers and molecular analyses (ctDNA, transcriptome, miRNA-arrays). In addition, circulating tumor-DNA will be analyzed in patients with the best and the worst responses to the neoadjuvant treatment. The study was initiated in March 2015 in 26 centers for pancreatic surgery in Germany.DiscussionThe NEONAX trial is an innovative study on resectable pancreatic cancer and currently one of the largest trials in this field of research. It addresses the question of the role of intensified perioperative treatment with nab-paclitaxel plus gemcitabine in resectable pancreatic cancers to improve disease-free survival and offers a unique potential for translational research.Trial registrationClinicalTrials.gov: NCT02047513, 08/13/2014.

引用

页数：10

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