The combination of CDDP and ARA-C has shown some clinical efficiency as first-line therapy in advanced colorectal cancer. Our study was aimed to evaluate the therapeutic activity of this combination in advanced colorectal cancer who failed 5-fluorouracil (FU) and folinic acid (LV) regimen. Seventeen patients with measureable metastatic colorectal cancer who failed 5FU-LV therapy as first line (n = 14) or second line treatment (n = 3), entered the study. Three patients who recurred during adjuvant treatment with 5FU and levamisol, were also included. Median age was 59.5 (40-69). Performance status was as follows: 0 (n = 5), 1 (n = 11), 2 (n = 3), 3 (n = 1). Site of metastases included liver (n = 16), lung (n = 7), abdomen (n = 2), pelvic recurrences (n = 2), cutaneous (n = 1). Seven patients had 2 metastatic sites and two 3. The treatment was given as follows: ARA-C 75 mg/m2/day, days 1-3, followed 1 hour later by CDDP 30 mg/m2/day, days 1-3, every 28 days. The median number of cycles was 3 (range: 1-6 cycles). All patients but one were evaluable for both response and toxicity. Of these patients, 50% experienced severe hematologic toxicity and nonhematologic toxicity mainly consisted of fatigue and/or vomiting. No objective response was observed, but there were 3 stabilizations and 16 progressive diseases. Median time to progression was 10 weeks. Thus, the CDDP/ARA-C regimen is not of clinical value as salvage therapy in advanced colorectal cancer because of its toxicity and its lack of efficiency.