Is repeated treatment with a 5-fluorouracil-based regimen useful in colorectal cancer?

Salvage treatment with 5-fluorouracil (5-FU) with or without leucovorin may induce responses in patients with advanced colorectal cancer whose disease progresses after adjuvant therapy with the same drugs. Similarly, restarting a regimen containing 5-FU can be beneficial in patients with advanced disease who had previously responded to the therapy or experienced disease stabilization but whose treatment was interrupted. Administering 5-FU by continuous intravenous (i.v.) infusion may result in a tumor response after disease progression on bolus 5-FU i.v. injection. Adding the platinum compound oxaliplatin to 5-FU and leucovorin may provide synergistic antineoplastic activity, even in patients with disease refractory to 5-FU. Chronomodulation of therapy decreases toxicity and increases dose intensity, response rate, and possibly survival time in some studies. Hepatic arterial infusion of chemotherapeutic agents is not routinely recommended in patients who have metastases limited to the liver and whose disease has failed to respond to prior 5-FU because of the associated costs and complications and the lack of data supporting the use of this approach after disease progression on i.v. 5-FU. A multicenter phase III trial has been completed in which patients whose colorectal cancer had progressed after first-line treatment with 5-FU were randomized to receive irinotecan 300 to 350 mg/m2 every 3 weeks or infusional 5-FU with or without leucovorin (Proc Am Soc Clin Oncol 17:256A, 1998 [abstr 984]). The 5-FU was administered according to investigator choice as a 24-hour, 48-hour, or continuous infusion. The results of this trial, which have been submitted for publication, should help to clarify the relative value of re-treatment with a 5-FU-containing regimen versus use of irinotecan in patients with disease progression after first-line 5-FU.