Long-course oxaliplatin-based preoperative chemoradiation versus 5 x 5 Gy and consolidation chemotherapy for cT4 or fixed cT3 rectal cancer: results of a randomized phase III study

被引：332

作者：

Bujko, K. ^{[1
]}

Wyrwicz, L. ^{[2
]}

Rutkowski, A. ^{[2
]}

Malinowska, M. ^{[3
]}

Pietrzak, L. ^{[1
]}

Krynski, J. ^{[2
,6
]}

Michalski, W. ^{[4
]}

Oledzki, J. ^{[5
]}

Kusnierz, J.

Zajac, L. ^{[2
]}

Bednarczyk, M. ^{[2
]}

Szczepkowski, M. ^{[7
,8
]}

Tarnowski, W. ^{[9
]}

Kosakowska, E. ^{[2
]}

Zwolinski, J. ^{[2
]}

Winiarek, M. ^{[2
]}

Wisniowska, K. ^{[1
]}

Partycki, M. ^{[1
]}

Beczkowska, K. ^{[1
]}

Polkowski, W. ^{[10
]}

Stylinski, R. ^{[11
]}

Wierzbicki, R. ^{[12
]}

Bury, P. ^{[13
]}

Jankiewicz, M. ^{[10
,14
]}

Paprota, K. ^{[14
]}

Lewicka, M. ^{[10
]}

Cisel, B. ^{[10
]}

Skorzewska, M. ^{[10
]}

Mielko, J. ^{[10
]}

Bebenek, M. ^{[15
]}

Maciejczyk, A. ^{[16
]}

Kapturkiewicz, B. ^{[15
]}

Dybko, A. ^{[17
]}

Hajac, L. ^{[17
]}

Wojnar, A. ^{[18
]}

Lesniak, T. ^{[19
]}

Zygulska, J. ^{[20
]}

Jantner, D.

Chudyba, E. ^{[20
]}

Zegarski, W. ^{[21
]}

Las-Jankowska, M. ^{[21
]}

Jankowski, M. ^{[21
]}

Kolodziejski, L. ^{[22
]}

Radkowski, A. ^{[23
]}

Zelazowska-Omiotek, U. ^{[23
]}

Czeremszynska, B. ^{[24
,25
]}

Kepka, L. ^{[24
,25
]}

Kolb-Sielecki, J. ^{[24
,25
]}

Toczko, Z. ^{[26
]}

Fedorowicz, Z. ^{[26
]}

机构：

[1] M Sklodowska Curie Mem Canc Ctr, Dept Radiotherapy, WK Roentgena 5, PL-02781 Warsaw, Poland

[2] M Sklodowska Curie Mem Canc Ctr, Dept Gastroenterol Oncol, Warsaw, Poland

[3] M Sklodowska Curie Mem Canc Ctr, Dept Pathol, Warsaw, Poland

[4] M Sklodowska Curie Mem Canc Ctr, Bioinformat & Biostat Unit, Warsaw, Poland

[5] Med Univ Warsaw, Dept Colorectal Surg, Warsaw, Poland

[6] M Sklodowska Curie Mem Canc Ctr, Dept Gynecol, Warsaw, Poland

[7] Jozef Pilsudski Univ Phys Educ, Dept Rehabil, Warsaw, Poland

[8] Bielanski Hosp, Clin Dept Gen & Colorectal Surg, Warsaw, Poland

[9] Orlowski Hosp, Med Ctr Postgrad Educ, Dept Gen Oncol & Digest Tract Surg, Warsaw, Poland

[10] Med Univ Lublin, Dept Surg Oncol, Lublin, Poland

[11] Med Univ Lublin, Dept Gen Surg Transplantol & Nutr Therapy 1, Lublin, Poland

[12] MSW Hosp, Dept Surg, Lublin, Poland

[13] Med Univ Lublin, Chair & Dept Gen & Gastrointestinal Surg & Surg O, Lublin, Poland

[14] St Johns Canc Ctr, Dept Radiotherapy, Lublin, Poland

[15] Silesian Oncol Ctr, Dept Surg, Wroclaw, Poland

[16] Silesian Oncol Ctr, Dept Radiotherapy, Wroclaw, Poland

[17] Silesian Oncol Ctr, Dept Med Oncol, Wroclaw, Poland

[18] Silesian Oncol Ctr, Dept Pathol, Wroclaw, Poland

[19] Beskid Ctr Oncol, Dept Surg, Bielsko Biala, Poland

[20] Beskid Ctr Oncol, Dept Radiotherapy, Bielsko Biala, Poland

[21] Nicolaus Copernicus Univ & Oncol Ctr, Coll Med, Dept Surg Oncol, Bydgoszcz, Poland

[22] Reg Canc Ctr, Dept Surg, Tarnow, Poland

[23] Reg Canc Ctr, Dept Radiotherapy, Tarnow, Poland

[24] Minist Interior, Independent Publ Hlth Care Facil, Dept Radiotherapy, Olsztyn, Poland

[25] Warmian Masurian Oncol Ctr, Olsztyn, Poland

[26] Reg Hosp, Dept Surg, Elblag, Poland

[27] Med Univ Lodz, Dept Surg, Lodz, Poland

[28] M Sklodowska Curie Mem Canc Ctr, Dept Surg, Warsaw, Poland

[29] Reg Canc Ctr, Dept Surg, Bialystok, Poland

[30] Reg Oncol Ctr, Dept Radiotherapy, Kielce, Poland

[31] M Sklodowska Curie Mem Canc Ctr, Dept Radiotherapy, Gliwice, Poland

来源：

ANNALS OF ONCOLOGY | 2016年 / 27卷 / 05期

关键词：

rectal cancer; preoperative chemoradiation; SHORT-COURSE RADIOTHERAPY; RADIATION-THERAPY; POSTOPERATIVE CHEMOTHERAPY; FOLFOX CHEMOTHERAPY; INTERIM ANALYSIS; DELAYED SURGERY; TRIAL; CHEMORADIOTHERAPY; FLUOROURACIL; CAPECITABINE;

D O I：

10.1093/annonc/mdw062

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 [肿瘤学];

摘要：

This is a first phase III study to test preoperative short-course radiotherapy with consolidation chemotherapy (group A) against long-course chemoradiation (group B). Local effectiveness of the two methods was similar. Acute toxicity was lower in group A than in group B. Furthermore, results showed improved overall survival in group A compared with group B.Improvements in local control are required when using preoperative chemoradiation for cT4 or advanced cT3 rectal cancer. There is therefore a need to explore more effective schedules. Patients with fixed cT3 or cT4 cancer were randomized either to 5 x 5 Gy and three cycles of FOLFOX4 (group A) or to 50.4 Gy in 28 fractions combined with two 5-day cycles of bolus 5-Fu 325 mg/m(2)/day and leucovorin 20 mg/m(2)/day during the first and fifth week of irradiation along with five infusions of oxaliplatin 50 mg/m(2) once weekly (group B). The protocol was amended in 2012 to allow oxaliplatin to be then foregone in both groups. Of 541 entered patients, 515 were eligible for analysis; 261 in group A and 254 in group B. Preoperative treatment acute toxicity was lower in group A than group B, P = 0.006; any toxicity being, respectively, 75% versus 83%, grade III-IV 23% versus 21% and toxic deaths 1% versus 3%. R0 resection rates (primary end point) and pathological complete response rates in groups A and B were, respectively, 77% versus 71%, P = 0.07, and 16% versus 12%, P = 0.17. The median follow-up was 35 months. At 3 years, the rates of overall survival and disease-free survival in groups A and B were, respectively, 73% versus 65%, P = 0.046, and 53% versus 52%, P = 0.85, together with the cumulative incidence of local failure and distant metastases being, respectively, 22% versus 21%, P = 0.82, and 30% versus 27%, P = 0.26. Postoperative and late complications rates in group A and group B were, respectively, 29% versus 25%, P = 0.18, and 20% versus 22%, P = 0.54. No differences were observed in local efficacy between 5 x 5 Gy with consolidation chemotherapy and long-course chemoradiation. Nevertheless, an improved overall survival and lower acute toxicity favours the 5 x 5 Gy schedule with consolidation chemotherapy. The trial is registered as ClinicalTrials.gov number NCT00833131.

引用

页码：834 / 842

页数：9

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