Randomized phase II study of neoadjuvant combined-modality chemoradiation for distal rectal cancer: Radiation Therapy Oncology Group Trial 0012

J Clin Oncol. 2006 Feb 1;24(4):650-5. doi: 10.1200/JCO.2005.03.6095.

Abstract

Purpose: 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

Patients and 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.

Conclusion: 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.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Camptothecin / administration & dosage
  • Camptothecin / adverse effects
  • Camptothecin / analogs & derivatives
  • Chemotherapy, Adjuvant / adverse effects
  • Dose Fractionation, Radiation
  • Drug Administration Schedule
  • Female
  • Fluorouracil / administration & dosage
  • Fluorouracil / adverse effects
  • Humans
  • Infusions, Intravenous
  • Irinotecan
  • Male
  • Middle Aged
  • Neoadjuvant Therapy / adverse effects
  • Neoadjuvant Therapy / methods*
  • Radiotherapy, Adjuvant / adverse effects
  • Rectal Neoplasms / drug therapy*
  • Rectal Neoplasms / radiotherapy*
  • Rectal Neoplasms / surgery
  • Treatment Outcome

Substances

  • Irinotecan
  • Fluorouracil
  • Camptothecin