title: Randomized phase II study of neoadjuvant combined-modality chemoradiation for distal rectal cancer: Radiation Therapy Oncology Group Trial 0012.
abstract: OBJECTIVE
  To evaluate the rate of pathologic complete response and toxicity of neoadjuvant chemoradiation for advanced T3/T4 distal rectal cancers in a randomized phase II study
  
  
  METHODS
  Patients with clinical T3/T4 distal rectal cancers were randomly assigned in a phase II study to receive combined neoadjuvant chemoradiotherapy followed by surgical resection. Patients were randomly assigned to receive continuous venous infusion (CVI) fluorouracil (FU) 225 mg/m2 per day, 7 days per week, plus pelvic hyperfractionated radiation 55.2 to 60 Gy at 1.2 Gy bid (arm 1) or CVI FU 225 mg/m2 per day Monday to Friday, 120 hours per week plus irinotecan 50 mg/m2 once weekly for 4 weeks plus pelvic radiation therapy 50.4 to 54 Gy at 1.8 Gy per day (arm 2). Surgery was performed 4 to 10 weeks after completion of neoadjuvant therapy. The primary end point of this study was pathologic complete response (pCR). Secondary end points included acute and late normal tissue morbidity.
  
  
  RESULTS
  A total of 106 patients were entered onto the study, with 103 assessable for response. The overall resectability rate was 93%. The median time to surgery was 7 weeks. Tumor downstaging was observed in 78% of patients in both arms. The pCR rate for all assessable patients was 26% in each arm. For patients who had surgery, the pCR rate was also the same (28%) in both arms. Acute and late toxicity was also similar. Grade 3 and 4 acute hematologic and nonhematologic toxicity occurred in 13% and 38% in arm 1 and 12% and 45% in arm 2, respectively.
  
  
  CONCLUSIONS
  Although the overall complete response rate and toxicity seems similar in both arms, this is the first multi-institutional study to establish a relatively high (28%) pCR rate after neoadjuvant therapy.
authors.affiliation: Geisinger Cancer Institute, Wilkes-Barre, PA 18711, USA. mmohiuddin1@geisinger.edu
authors.forename: Mohammed
authors.initials: M
authors.lastname: Mohiuddin
authors.forename: Kathryn
authors.initials: K
authors.lastname: Winter
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: Charles
authors.initials: C
authors.lastname: Nichols
authors.forename: Robert
authors.initials: R
authors.lastname: Shane
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; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002166:Camptothecin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D017024:Chemotherapy, Adjuvant / Q000009:adverse effects; D019583:Dose Fractionation, Radiation; D004334:Drug Administration Schedule; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects; D006801:Humans; D007262:Infusions, Intravenous; D000077146:Irinotecan; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy / Q000009:adverse effects / Q000379:methods*; D018714:Radiotherapy, Adjuvant / Q000009:adverse effects; D012004:Rectal Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy* / Q000601:surgery; D016896:Treatment Outcome
chemical_list: D000077146:Irinotecan; D005472:Fluorouracil; D002166:Camptothecin