Intergroup 0144 - phase III trial of 5-FU based chemotherapy regimens plus radiotherapy (XRT) in postoperative adjuvant rectal cancer. Bolus 5-FU vs prolonged venous infusion (PVI) before and after XRT + PVI vs bolus 5-FU + leukovorin (LV) + levamisole (

Reviewer: Walter Sall, MD
Last Modified: June 1, 2003

Presenter: S.R. Smalley
Presenter's Affiliation: SWOG
Type of Session: Scientific


  • 5-FU based chemoradiotherapy is standard post-operative management of T3-4N0 or node positive rectal cancer patients. Controversy regarding the optimal method of 5-FU delivery exists.
  • The Intergroup 864751 trial suggested improved RFS and OS in patients treated with PVI 5-FU during RT vs bolus 5-FU.
  • This trial studied pre and post-radiotherapy bolus 5-FU with concurrent PVI vs PVI 5-FU before, during and after XRT vs biochemically modulated bolus 5-FU with no PVI, thus avoiding central line placement

Materials and Methods

  • This is a three arm prospective, randomized trial.
  • Eligible patients included completely resected T3-4N0 or T1-4N1-3 rectal cancer patients. 1917 patients were randomized between 1994 and 2000.
  • Median follow up was 5 years.
  • Patients were stratified by type of operation, nodal stage, T stage and time from surgery to registration.
  • Arm 1 patients received 2 five day cycles of bolus 5-FU before and after XRT (50.4 - 54Gy) plus PVI 5-FU during XRT. Arm 2 patients received PVI 5-FU 42 days before, during and 56 days after XRT. Arm 3 patients received 2 five day cycles of bolus 5-FU with leucovorin before and after XRT and bolus 5-FU/leucovorin during XRT. Lev was also given before and after XRT in this arm.


  • Toxicity was similar with 1% lethal toxicity in all arms. However, Grade III/IV hematologic toxicity was about 50% in the two bolus arms vs 4% in the all PVI arm.
  • RFS and OS was similar in all arms with 3 year OS of 81-83%.
  • However when comparing arm 1 only to arm 2, 5 year OS was 67% vs 72% (one sided p=0.04) with the trend favoring all PVI 5-FU.

Author's Conclusions

  • A nonsignificant trend towards improved OS with all PVI 5-FU was seen. This deserves further investigation but is not sufficient to make this regimen the standard.
  • Bolus regimens with no PVI are effective and especially useful if a central line needs to be avoided.
  • Further study is needed to determine if the added toxicity and cost of PVI drug delivery is justified by the potential clinical benefit.

Clinical/Scientific Implications

    This study provides evidence that there is no dramatic difference in efficacy between different administration schedules of 5-FU for adjuvant rectal cancer treatment. This provides flexibility for the clinician to choose a regimen based on factors such as desired toxicity profile, demands of the patient and ability to place a central line. Further prospective studies of PVI 5-FU vs bolus are needed in order to determine if the non-significant trend towards improved OS with PVI seen in this study truly exists. For the moment any of these regimens are acceptable in clinical practice.

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