title: Long-course oxaliplatin-based preoperative chemoradiation versus 5 × 5 Gy and consolidation chemotherapy for cT4 or fixed cT3 rectal cancer: results of a randomized phase III study.
abstract: 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 × 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 × 5 Gy with consolidation chemotherapy and long-course chemoradiation. Nevertheless, an improved overall survival and lower acute toxicity favours the 5 × 5 Gy schedule with consolidation chemotherapy.
  
  
  
  The trial is registered as ClinicalTrials.gov number NCT00833131.
authors.affiliation: Department of Radiotherapy bujko@coi.waw.pl.
authors.forename: K
authors.initials: K
authors.lastname: Bujko
authors.affiliation: Department of Gastroenterological Oncology.
authors.forename: L
authors.initials: L
authors.lastname: Wyrwicz
authors.affiliation: Department of Gastroenterological Oncology.
authors.forename: A
authors.initials: A
authors.lastname: Rutkowski
authors.affiliation: Department of Pathology.
authors.forename: M
authors.initials: M
authors.lastname: Malinowska
authors.affiliation: Department of Radiotherapy.
authors.forename: L
authors.initials: L
authors.lastname: Pietrzak
authors.affiliation: Department of Gastroenterological Oncology.
authors.forename: J
authors.initials: J
authors.lastname: Kryński
authors.affiliation: Department of Bioinformatics and Biostatistics Unit, M. Skłodowska-Curie Memorial Cancer Centre, Warsaw.
authors.forename: W
authors.initials: W
authors.lastname: Michalski
authors.affiliation: Department of Colorectal Surgery, Medical University, Warsaw.
authors.forename: J
authors.initials: J
authors.lastname: Olędzki
authors.affiliation: Department of Gynecology, M. Skłodowska-Curie Memorial Cancer Centre, Warsaw.
authors.forename: J
authors.initials: J
authors.lastname: Kuśnierz
authors.affiliation: Department of Gastroenterological Oncology.
authors.forename: L
authors.initials: L
authors.lastname: Zając
authors.affiliation: Department of Gastroenterological Oncology.
authors.forename: M
authors.initials: M
authors.lastname: Bednarczyk
authors.affiliation: Department of Rehabilitation, Jozef Piłsudski University of Physical Education, Warsaw Clinical Department of General and Colorectal Surgery, Bielański Hospital, Warsaw.
authors.forename: M
authors.initials: M
authors.lastname: Szczepkowski
authors.affiliation: Department of General, Oncologic and Digestive Tract Surgery, Medical Centre of Postgraduate Education, Orłowski Hospital, Warsaw.
authors.forename: W
authors.initials: W
authors.lastname: Tarnowski
authors.affiliation: Department of Gastroenterological Oncology.
authors.forename: E
authors.initials: E
authors.lastname: Kosakowska
authors.affiliation: Department of Gastroenterological Oncology.
authors.forename: J
authors.initials: J
authors.lastname: Zwoliński
authors.affiliation: Department of Gastroenterological Oncology.
authors.forename: M
authors.initials: M
authors.lastname: Winiarek
authors.affiliation: Department of Radiotherapy.
authors.forename: K
authors.initials: K
authors.lastname: Wiśniowska
authors.affiliation: Department of Radiotherapy.
authors.forename: M
authors.initials: M
authors.lastname: Partycki
authors.affiliation: Department of Radiotherapy.
authors.forename: K
authors.initials: K
authors.lastname: Bęczkowska
authors.affiliation: Department of Surgical Oncology, Medical University of Lublin, Lublin.
authors.forename: W
authors.initials: W
authors.lastname: Polkowski
authors.affiliation: First Department of General Surgery, Transplantology and Nutritional Therapy, Medical University of Lublin, Lublin.
authors.forename: R
authors.initials: R
authors.lastname: Styliński
authors.affiliation: Department of Surgery, MSW Hospital, Lublin.
authors.forename: R
authors.initials: R
authors.lastname: Wierzbicki
authors.affiliation: II Chair and Department of General and Gastrointestinal Surgery and Surgical Oncology of the Alimentary Tract, Medical University, Lublin.
authors.forename: P
authors.initials: P
authors.lastname: Bury
authors.affiliation: Department of Surgical Oncology, Medical University of Lublin, Lublin Department of Radiotherapy, St John's Cancer Center, Lublin.
authors.forename: M
authors.initials: M
authors.lastname: Jankiewicz
authors.affiliation: Department of Radiotherapy, St John's Cancer Center, Lublin.
authors.forename: K
authors.initials: K
authors.lastname: Paprota
authors.affiliation: Department of Surgical Oncology, Medical University of Lublin, Lublin.
authors.forename: M
authors.initials: M
authors.lastname: Lewicka
authors.affiliation: Department of Surgical Oncology, Medical University of Lublin, Lublin.
authors.forename: B
authors.initials: B
authors.lastname: Ciseł
authors.affiliation: Department of Surgical Oncology, Medical University of Lublin, Lublin.
authors.forename: M
authors.initials: M
authors.lastname: Skórzewska
authors.affiliation: Department of Surgical Oncology, Medical University of Lublin, Lublin.
authors.forename: J
authors.initials: J
authors.lastname: Mielko
authors.affiliation: Department of Surgery.
authors.forename: M
authors.initials: M
authors.lastname: Bębenek
authors.affiliation: Department of Radiotherapy.
authors.forename: A
authors.initials: A
authors.lastname: Maciejczyk
authors.affiliation: Department of Surgery.
authors.forename: B
authors.initials: B
authors.lastname: Kapturkiewicz
authors.affiliation: Medical Oncology.
authors.forename: A
authors.initials: A
authors.lastname: Dybko
authors.affiliation: Medical Oncology.
authors.forename: Ł
authors.initials: Ł
authors.lastname: Hajac
authors.affiliation: Pathology, Silesian Oncological Centre, Wroclaw.
authors.forename: A
authors.initials: A
authors.lastname: Wojnar
authors.affiliation: Department of Surgery, Beskid Centre of Oncology, Bielsko-Biala.
authors.forename: T
authors.initials: T
authors.lastname: Leśniak
authors.affiliation: Department of Radiotherapy, Beskid Centre of Oncology, Bielsko-Biala.
authors.forename: J
authors.initials: J
authors.lastname: Zygulska
authors.affiliation: Department of Surgery, Beskid Centre of Oncology, Bielsko-Biala.
authors.forename: D
authors.initials: D
authors.lastname: Jantner
authors.affiliation: Department of Radiotherapy, Beskid Centre of Oncology, Bielsko-Biala.
authors.forename: E
authors.initials: E
authors.lastname: Chudyba
authors.affiliation: Department of Oncological Surgery, Collegium Medicum Nicolaus Copernicus University and Oncology Centre, Bydgoszcz.
authors.forename: W
authors.initials: W
authors.lastname: Zegarski
authors.affiliation: Department of Oncological Surgery, Collegium Medicum Nicolaus Copernicus University and Oncology Centre, Bydgoszcz.
authors.forename: M
authors.initials: M
authors.lastname: Las-Jankowska
authors.affiliation: Department of Oncological Surgery, Collegium Medicum Nicolaus Copernicus University and Oncology Centre, Bydgoszcz.
authors.forename: M
authors.initials: M
authors.lastname: Jankowski
authors.affiliation: Department of Surgery.
authors.forename: L
authors.initials: L
authors.lastname: Kołodziejski
authors.affiliation: Department of Radiotherapy, Regional Cancer Centre, Tarnów.
authors.forename: A
authors.initials: A
authors.lastname: Radkowski
authors.affiliation: Department of Radiotherapy, Regional Cancer Centre, Tarnów.
authors.forename: U
authors.initials: U
authors.lastname: Żelazowska-Omiotek
authors.affiliation: Department Radiotherapy, Independent Public Health Care Facility of the Ministry of the Interior and Warmian-Masurian Oncology Centre, Olsztyn.
authors.forename: B
authors.initials: B
authors.lastname: Czeremszyńska
authors.affiliation: Department Radiotherapy, Independent Public Health Care Facility of the Ministry of the Interior and Warmian-Masurian Oncology Centre, Olsztyn.
authors.forename: L
authors.initials: L
authors.lastname: Kępka
authors.affiliation: Department Radiotherapy, Independent Public Health Care Facility of the Ministry of the Interior and Warmian-Masurian Oncology Centre, Olsztyn.
authors.forename: J
authors.initials: J
authors.lastname: Kolb-Sielecki
authors.affiliation: Department of Surgery, Regional Hospital, Elbląg.
authors.forename: Z
authors.initials: Z
authors.lastname: Toczko
authors.affiliation: Department of Surgery, Regional Hospital, Elbląg.
authors.forename: Z
authors.initials: Z
authors.lastname: Fedorowicz
authors.affiliation: Department of Surgery, Medical University, Lódź
authors.forename: A
authors.initials: A
authors.lastname: Dziki
authors.affiliation: Department of Radiotherapy.
authors.forename: A
authors.initials: A
authors.lastname: Danek
authors.affiliation: Department of Surgery, M. Skłodowska-Curie Memorial Cancer Centre, Warsaw.
authors.forename: G
authors.initials: G
authors.lastname: Nawrocki
authors.affiliation: Department of Surgery, M. Skłodowska-Curie Memorial Cancer Centre, Warsaw.
authors.forename: R
authors.initials: R
authors.lastname: Sopyło
authors.affiliation: Department of Surgery, Regional Cancer Centre, Białystok.
authors.forename: W
authors.initials: W
authors.lastname: Markiewicz
authors.affiliation: Department of Radiotherapy, Regional Oncological Centre, Kielce.
authors.forename: P
authors.initials: P
authors.lastname: Kędzierawski
authors.affiliation: Department of Radiotherapy, M. Skłodowska-Curie Memorial Cancer Centre, Gliwice, Poland.
authors.forename: J
authors.initials: J
authors.lastname: Wydmański
mesh_terms: D000368:Aged; D059248:Chemoradiotherapy; D003131:Combined Modality Therapy; D060830:Consolidation Chemotherapy; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D009944:Organoplatinum Compounds / Q000008:administration & dosage*; D000077150:Oxaliplatin; D011300:Preoperative Care; D011879:Radiotherapy Dosage; D012004:Rectal Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy* / Q000601:surgery
chemical_list: D009944:Organoplatinum Compounds; D000077150:Oxaliplatin
keywords: preoperative chemoradiation; rectal cancer