title: Neoadjuvant chemoradiation for distal rectal cancer: 5-year updated results of a randomized phase 2 study of neoadjuvant combined modality chemoradiation for distal rectal cancer.
abstract: OBJECTIVE
  To assess the efficacy of 2 different approaches to neoadjuvant chemoradiation for distal rectal cancers.
  
  
  METHODS
  One hundred six patients with T3/T4 distal rectal cancers were randomized in a phase 2 study. Patients received either continuous venous infusion (CVI) of 5-Fluorouracil (5-FU), 225 mg/m(2) per day, 7 days per week plus pelvic hyperfractionated radiation (HRT), 45.6 Gy at 1.2 Gy twice daily plus a boost of 9.6 to 14.4 Gy for T3 or T4 cancers (Arm 1), or CVI of 5-FU, 225 mg/m(2) per day, Monday to Friday, plus irinotecan, 50 mg/m(2) once weekly × 4, plus pelvic radiation therapy (RT), 45 Gy at 1.8 Gy per day and a boost of 5.4 Gy for T3 and 9 Gy for T4 cancers (Arm 2). Surgery was performed 4 to 10 weeks later.
  
  
  RESULTS
  All eligible patients (n=103) are included in this analysis; 2 ineligible patients were excluded, and 1 patient withdrew consent. Ninety-eight of 103 patients (95%) underwent resection. Four patients did not undergo surgery for either disease progression or patient refusal, and 1 patient died during induction chemotherapy. The median time of follow-up was 6.4 years in Arm 1 and 7.0 years in Arm 2. The pathological complete response (pCR) rates were 30% in Arm 1 and 26% in Arm 2. Locoregional recurrence rates were 16% in Arm 1 and 17% in Arm 2. Five-year survival rates were 61% and 75% and Disease-specific survival rates were 78% and 85% for Arm1 and Arm 2, respectively. Five second primaries occurred in patients on Arm 1, and 1 second primary occurred in Arm 2.
  
  
  CONCLUSIONS
  High rates of disease-specific survival were seen in each arm. Overall survival appears affected by the development of unrelated second cancers. The high pCR rates with 5-FU and higher dose radiation in T4 cancers provide opportunity for increased R0 resections and improved survival.
authors.affiliation: King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia. asemuddin@gmail.com
authors.forename: Mohammed
authors.initials: M
authors.lastname: Mohiuddin
authors.forename: Rebecca
authors.initials: R
authors.lastname: Paulus
authors.forename: Edith
authors.initials: E
authors.lastname: Mitchell
authors.forename: Nader
authors.initials: N
authors.lastname: Hanna
authors.forename: Albert
authors.initials: A
authors.lastname: Yuen
authors.forename: Romaine
authors.initials: R
authors.lastname: Nichols
authors.forename: Salochna
authors.initials: S
authors.lastname: Yalavarthi
authors.forename: Cherie
authors.initials: C
authors.lastname: Hayostek
authors.forename: Christopher
authors.initials: C
authors.lastname: Willett
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000465:Algorithms; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives*; D059248:Chemoradiotherapy / Q000379:methods*; D018572:Disease-Free Survival; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage*; D006801:Humans; D007262:Infusions, Intravenous / Q000379:methods; D000077146:Irinotecan; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy / Q000379:methods*; D011879:Radiotherapy Dosage; D012004:Rectal Neoplasms / Q000401:mortality / Q000473:pathology / Q000601:surgery / Q000628:therapy*; D015996:Survival Rate; D017211:Treatment Failure; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D000077146:Irinotecan; D005472:Fluorouracil; D002166:Camptothecin
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