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The combination of 5-fluorouracil (5-FU) modulated by folinic acid (FA) and cisplatin is commonly used in advanced digestive non-colon cancers (ADNCC). In order to simplify treatment administration by avoiding cisplatin-related hydration, we investigated a weekly regimen of 5-FU/FA/cisplatin. Patients with ADNCC were treated with 5-FU 2.0 g/m2, FA 500 mg/m2 and cisplatin 25 mg/m2 day 1, for 6 weeks with a 2-week rest, and were assessed for toxicity, tumor response and disease-free survival. Forty-three patients with measurable ADNCC were treated with this weekly regimen. Primary tumor sites were mainly esophagus (n = 17), stomach (n = 12) and pancreas (n = 9). Results were as follows. Toxicity was mostly hematological, with 16% grade 3/4 neutropenia (seven of 43) and 4% febrile neutropenia (two of 43). Objective response (OR) was observed in 19 of 43 (44%) patients including four complete responses (9%) and 15 partial responses (35%). Another 18 patients (42%) experienced stable disease. Time to progression was 6.5 months. The median response and stable disease durations were 4.3 (range 3-34) and 5 (range 2-16) months, respectively. We conclude that weekly administration of 5-FU/FA/cisplatin is an active and well-tolerated regimen. Toxicity is manageable and allows chemotherapy on an outpatient basis without hydration program as required when cisplatin is used at the dose of 50 mg/m2.

The goal of the present paper is to review how treatment of advanced colorectal cancer has evolved during the last 10 years and to make some suggestions on how that disease could be managed today. 5-Fluorouracil (5-FU) combined with folinic acid (FA) remains the basis for advanced colorectal cancer treatment. In Europe, infusional 5-FU is considered to be more active and better tolerated than bolus 5-FU. New agents including oral 5-FU prodrugs UFT/FA, and capecitabine, tomudex, irinotecan and oxaliplatin have been shown active in advanced colorectal cancer. At presentation the combination of infusional 5-FU/FA with irinotecan or oxaliplatin is considered to be superior to any of these agents used alone, yielding a median survival of up to 16-19 months. Second-line therapy could further prolong survival in selected patient populations. Eventually chemotherapy could allow curative resection of previously unresectable hepatic and pulmonary metastases.

Patients with colorectal carcinoma progressing after a 5-fluorouracil (5-FU)-containing regimen were eligible. One treatment cycle consisted of repeated administrations of 5-FU combined to folinic acid for six times and to oxaliplatin for three times over 50 days. 5-FU was given at the dose of 2.6 g/m2 as a continuous infusion over 24 h on days 1, 8, 22, 29 and 43 preceded by i.v. folinic acid (FA) at a dose of 500 mg/m2 over 1 h. Oxaliplatin was given 1 h after 5-FU at the dose of 130 mg/m2 over a 2 h infusion on days 1, 22 and 43. A total of 37 patients were treated according to this schedule. The rates of objective responses after the first and second treatment cycles were 28 and 17%, respectively, with rates of tumor growth control, i.e. including the stabilizations, of 55 and 28%. The median duration of response was 10 months and the median duration of stabilizations was 6 months. The median survival time from initiation of oxaliplatin-containing therapy is 10 months (2-28+). The median survival time from the diagnosis of metastatic disease is 24 months (2-40+). The main toxicities were leucopenia, diarrhea, fatigue and paresthesias. The combination of 5-FU/FA/oxaliplatin was well tolerated and appears as a meaningful therapy after failure of a previous 5-FU-containing treatment.