title: Randomized phase III study comparing preoperative radiotherapy with chemoradiotherapy in nonresectable rectal cancer.
abstract: OBJECTIVE
  Preoperative chemoradiotherapy is considered standard treatment for locally advanced rectal cancer, although the scientific evidence for the chemotherapy addition is limited. This trial investigated whether chemotherapy as part of a multidisciplinary treatment approach would improve downstaging, survival, and relapse rate.
  
  
  METHODS
  The randomized study included 207 patients with locally nonresectable T4 primary rectal carcinoma or local recurrence from rectal carcinoma in the period 1996 to 2003. The patients received either chemotherapy (fluorouracil/leucovorin) administered concurrently with radiotherapy (50 Gy) and adjuvant for 16 weeks after surgery (CRT group, n = 98) or radiotherapy alone (50 Gy; RT group, n = 109).
  
  
  RESULTS
  The two groups were well balanced according to pretreatment characteristics. An R0 resection was performed in 82 patients (84%) in the CRT group and in 74 patients (68%) in the RT group (P = .009). Pathologic complete response was seen in 16% and 7%, respectively. After an R0 + R1 resection, local recurrence was found in 5% and 7%, and distant metastases in 26% and 39%, respectively. Local control (82% v 67% at 5 years; log-rank P = .03), time to treatment failure (63% v 44%; P = .003), cancer-specific survival (72% v 55%; P = .02), and overall survival (66% v 53%; P = .09) all favored the CRT group. Grade 3 or 4 toxicity, mainly GI, was seen in 28 (29%) of 98 and six (6%) of 109, respectively (P = .001). There was no difference in late toxicity.
  
  
  CONCLUSIONS
  CRT improved local control, time to treatment failure, and cancer-specific survival compared with RT alone in patients with nonresectable rectal cancer. The treatments were well tolerated.
authors.affiliation: Departments of Medical Oncology and Surgery, Norwegian Radium Hospital, Ullevål University Hospital, Cancer Centre, Oslo, Norway. morten.braendengen@ulleval.no
authors.forename: Morten
authors.initials: M
authors.lastname: Braendengen
authors.forename: Kjell M
authors.initials: KM
authors.lastname: Tveit
authors.forename: Ake
authors.initials: A
authors.lastname: Berglund
authors.forename: Elke
authors.initials: E
authors.lastname: Birkemeyer
authors.forename: Gunilla
authors.initials: G
authors.lastname: Frykholm
authors.forename: Lars
authors.initials: L
authors.lastname: Påhlman
authors.forename: Johan N
authors.initials: JN
authors.lastname: Wiig
authors.forename: Per
authors.initials: P
authors.lastname: Byström
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Bujko
authors.forename: Bengt
authors.initials: B
authors.lastname: Glimelius
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000401:mortality / Q000532:radiotherapy* / Q000601:surgery; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D017024:Chemotherapy, Adjuvant; D005060:Europe; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D002955:Leucovorin / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009364:Neoplasm Recurrence, Local; D018714:Radiotherapy, Adjuvant; D012004:Rectal Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000532:radiotherapy* / Q000601:surgery; D016019:Survival Analysis; D013997:Time Factors; D017211:Treatment Failure; D016896:Treatment Outcome
chemical_list: D002955:Leucovorin; D005472:Fluorouracil