title: Adjuvant chemotherapy for rectal cancer patients treated with preoperative (chemo)radiotherapy and total mesorectal excision: a Dutch Colorectal Cancer Group (DCCG) randomized phase III trial.
abstract: BACKGROUND
  The discussion on the role of adjuvant chemotherapy for rectal cancer patients treated according to current guidelines is still ongoing. A multicentre, randomized phase III trial, PROCTOR-SCRIPT, was conducted to compare adjuvant chemotherapy with observation for rectal cancer patients treated with preoperative (chemo)radiotherapy and total mesorectal excision (TME).
  
  
  METHODS
  The PROCTOR-SCRIPT trial recruited patients from 52 hospitals. Patients with histologically proven stage II or III rectal adenocarcinoma were randomly assigned (1:1) to observation or adjuvant chemotherapy after preoperative (chemo)radiotherapy and TME. Radiotherapy consisted of 5 × 5 Gy. Chemoradiotherapy consisted of 25 × 1.8-2 Gy combined with 5-FU-based chemotherapy. Adjuvant chemotherapy consisted of 5-FU/LV (PROCTOR) or eight courses capecitabine (SCRIPT). Randomization was based on permuted blocks of six, stratified according to centre, residual tumour, time between last irradiation and surgery, and preoperative treatment. The primary end point was overall survival.
  
  
  RESULTS
  Of 470 enrolled patients, 437 were eligible. The trial closed prematurely because of slow patient accrual. Patients were randomly assigned to observation (n = 221) or adjuvant chemotherapy (n = 216). After a median follow-up of 5.0 years, 5-year overall survival was 79.2% in the observation group and 80.4% in the chemotherapy group [hazard ratio (HR) 0.93, 95% confidence interval (CI) 0.62-1.39; P = 0.73]. The HR for disease-free survival was 0.80 (95% CI 0.60-1.07; P = 0.13). Five-year cumulative incidence for locoregional recurrences was 7.8% in both groups. Five-year cumulative incidence for distant recurrences was 38.5% and 34.7%, respectively (P = 0.39).
  
  
  CONCLUSIONS
  The PROCTOR-SCRIPT trial could not demonstrate a significant benefit of adjuvant chemotherapy with fluoropyrimidine monotherapy after preoperative (chemo)radiotherapy and TME on overall survival, disease-free survival, and recurrence rate. However, this trial did not complete planned accrual.
  
  
  BACKGROUND
  Dutch Colorectal Cancer group, CKTO 2003-16, ISRCTN36266738.
authors.affiliation: Department of Surgery, Leiden University Medical Centre, Leiden.
authors.forename: A J
authors.initials: AJ
authors.lastname: Breugom
authors.affiliation: Department of Surgery, Leiden University Medical Centre, Leiden.
authors.forename: W
authors.initials: W
authors.lastname: van Gijn
authors.affiliation: Department of Internal Medicine, Slingeland Hospital, Doetinchem, The Netherlands.
authors.forename: E W
authors.initials: EW
authors.lastname: Muller
authors.affiliation: Department of Radiology, Oncology and Radiation Science, Uppsala University, Uppsala.
authors.forename: Å
authors.initials: Å
authors.lastname: Berglund
authors.affiliation: Department of Surgery, Leiden University Medical Centre, Leiden.
authors.forename: C B M
authors.initials: CBM
authors.lastname: van den Broek
authors.affiliation: Department of Oncology and Pathology, Karolinska Institutet, Stockholm, Sweden.
authors.forename: T
authors.initials: T
authors.lastname: Fokstuen
authors.affiliation: Department of Clinical Oncology, Leiden University Medical Centre, Leiden.
authors.forename: H
authors.initials: H
authors.lastname: Gelderblom
authors.affiliation: Department of Clinical Oncology, Leiden University Medical Centre, Leiden.
authors.forename: E
authors.initials: E
authors.lastname: Kapiteijn
authors.affiliation: Department of Radiotherapy, Radboud University Medical Centre, Nijmegen.
authors.forename: J W H
authors.initials: JWH
authors.lastname: Leer
authors.affiliation: Department of Internal Medicine, Slingeland Hospital, Doetinchem, The Netherlands.
authors.forename: C A M
authors.initials: CAM
authors.lastname: Marijnen
authors.affiliation: Department of Radiotherapy, Catharina Hospital, Eindhoven.
authors.forename: H
authors.initials: H
authors.lastname: Martijn
authors.affiliation: Department of Surgery, Leiden University Medical Centre, Leiden.
authors.forename: E
authors.initials: E
authors.lastname: Meershoek-Klein Kranenbarg
authors.affiliation: Department of Pathology, Radboud University Medical Centre, Nijmegen, The Netherlands.
authors.forename: I D
authors.initials: ID
authors.lastname: Nagtegaal
authors.affiliation: Department of Surgical Sciences, Uppsala University, Uppsala, Sweden.
authors.forename: L
authors.initials: L
authors.lastname: Påhlman
authors.affiliation: Department of Medical Oncology, Academic Medical Centre, Amsterdam.
authors.forename: C J A
authors.initials: CJA
authors.lastname: Punt
authors.affiliation: Department of Medical Statistics and Bio-informatics, Leiden University Medical Centre, Leiden.
authors.forename: H
authors.initials: H
authors.lastname: Putter
authors.affiliation: Department of Surgery, Leiden University Medical Centre, Leiden.
authors.forename: A G H
authors.initials: AGH
authors.lastname: Roodvoets
authors.affiliation: Department of Surgery, Catharina Hospital, Eindhoven.
authors.forename: H J T
authors.initials: HJT
authors.lastname: Rutten
authors.affiliation: Department of Surgery, HAGA Hospital, The Hague, The Netherlands.
authors.forename: W H
authors.initials: WH
authors.lastname: Steup
authors.affiliation: Department of Radiology, Oncology and Radiation Science, Uppsala University, Uppsala; Department of Oncology and Pathology, Karolinska Institutet, Stockholm, Sweden.
authors.forename: B
authors.initials: B
authors.lastname: Glimelius
authors.affiliation: Department of Surgery, Leiden University Medical Centre, Leiden.
authors.forename: C J H
authors.initials: CJH
authors.lastname: van de Velde
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000069287:Capecitabine / Q000008:administration & dosage; D017024:Chemotherapy, Adjuvant; D003131:Combined Modality Therapy; D013505:Digestive System Surgical Procedures; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D005500:Follow-Up Studies; D006801:Humans; D015994:Incidence; D002955:Leucovorin / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000175:diagnosis* / Q000453:epidemiology*; D009367:Neoplasm Staging; D009426:Netherlands / Q000453:epidemiology; D011379:Prognosis; D018714:Radiotherapy, Adjuvant; D012004:Rectal Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D015996:Survival Rate
chemical_list: D000069287:Capecitabine; D002955:Leucovorin; D005472:Fluorouracil
keywords: adjuvant chemotherapy; preoperative chemoradiotherapy; preoperative radiotherapy; rectal adenocarcinoma; total mesorectal excision