Phase III trial of fluorouracil-based chemotherapy regimens plus radiotherapy in postoperative adjuvant rectal cancer: GI INT 0144

Stephen R. Smalley, Jacqueline K. Benedetti, Stephen K. Williamson, John M. Robertson, Norman C. Estes, Tracy Maher, Barbara Fisher, Tyvin A. Rich, James A. Martenson, John W. Kugler, Al B. Benson, Daniel G. Haller, Robert J. Mayer, James N. Atkins, Christine Cripps, John Pedersen, Phillip O. Periman, Michael S. Tanaka, Cynthia G. Leichman, John S. Macdonald

Research output: Contribution to journalArticlepeer-review

133 Scopus citations


Purpose: Adjuvant chemoradiotherapy after or before resection of high-risk rectal cancer improves overall survival (OS) and pelvic control. We studied three postoperative fluorouracil (FU) radiochemotherapy regimens. Patients and Methods: After resection of T3-4, N0, M0 or T1-4, N1, 2M0 rectal adenocarcinoma, 1,917 patients were randomly assigned to arm 1, with bolus FU in two 5-day cycles every 28 days before and after radiotherapy (XRT) plus FU via protracted venous infusion (PVI) 225 mg/m 2/d during XRT; arm 2 (PVI-only arm), with PVI 42 days before and 56 days after XRT + PVI; or arm 3 (bolus-only arm), with bolus FU + leucovorin (LV) in two 5-day cycles before and after XRT, plus bolus FU + LV (levamisole was administered each cycle before and after XRT). Patients were stratified by operation type, T and N stage, and time from surgery. Results: Median follow-up was 5.7 years. Lethal toxicity was less than 1%, with grade 3 to 4 hematologic toxicity in 49% to 55% of the bolus arms versus 4% in the PVI arm. No disease-free survival (DFS) or OS difference was detected (3-year DFS, 67% to 69% and 3-year OS, 81% to 83% in all arms). Locoregional failure (LRF) at first relapse was 8% in arm 1, 4.6% in arm 2, and 7% in arm 3. LRF in T1-2, N1-2, and T3, N0-2 primaries who received low anterior resection (those most suitable for primary resection) was 5% in arm 1, 3% in arm 2, and 5% in arm 3. Conclusion: All arms provide similar relapse-free survival and OS, with different toxicity profiles and central catheter requirements. LRF with postoperative therapy is low, justifying initial resection for T1-2, N0-2 and T3, and N0-2 anterior resection candidates.

Original languageEnglish (US)
Pages (from-to)3542-3547
Number of pages6
JournalJournal of Clinical Oncology
Issue number22
StatePublished - Aug 1 2006

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


Dive into the research topics of 'Phase III trial of fluorouracil-based chemotherapy regimens plus radiotherapy in postoperative adjuvant rectal cancer: GI INT 0144'. Together they form a unique fingerprint.

Cite this