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 (LEV) before and after XRT + bolus 5-FU + LV
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.
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.
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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