Five-day continuous infusion of 5-fluorouracil and pulsed folinic acid in patients with metastatic colorectal carcinoma: an effective second-line regimen.

OBJECTIVE: A previous phase I trial in 14 pretreated patients with progressive advanced colorectal cancer demonstrated 750 mg/m2 to be the maximum tolerable dose of 5-fluorouracil (5-FU) administered as a five-day continuous infusion modulated by short infusions of 100 mg/m2 folinic acid twice daily. The dose-limiting toxicities were hand-foot syndrome and severe mucositis. A response rate of 21% and 50% stable disease could be achieved. In order to determine the effectiveness and tolerability, we initiated a multicenter phase II trial applying a 650 mg/m2 recommended dose of 5-FU and 100 mg/m2 folinic acid twice daily every three weeks. PATIENTS AND METHODS: From January 1994 to July 1996, 88 advanced and progressive colorectal cancer patients either previously treated with a bolus schedule of 5-FU and folinic acid (34 patients) or without (54 patients) previous chemotherapy were included in this trial. RESULTS: In the group of previously treated patients, therapy led to 6% (2 of 34 patients) remissions while stable disease could be observed in 68% (23 of 34 patients) of the patients. The median survival time was 14 months. The main toxicity was mucositis grade 3 in 15% of the previously treated patients and 10% in the nonpretreated patients. In the population of nonpretreated patients, the overall response rate was 15% (eight of 54 patients) and stable disease could be induced in 67% (36 of 54 patients). The median survival time was 13.7 months. CONCLUSION: This regimen is an active second-line therapy in advanced colorectal cancer with minimal toxicity, thus preserving the quality of life during palliative chemotherapy. Antitumor activity in previously untreated patients does not seem superior to that obtained with weekly regimens applying 24- or 48-hour continuous infusions of 5-FU and folinic acid.

Soluble intercellular adhesion molecule-1 in colorectal cancer and its relationship to acute phase proteins.

Increased concentrations of soluble intercellular adhesion molecule-I (ICAM-1) have been reported in a number of diseases including cancer. This study was undertaken to evaluate soluble ICAM-1 in colorectal cancer and its relationship to an unspecific acute phase response. Fifty six patients (25 with advanced colorectal cancer and 31 out-patients after radical surgical treatment) were included. Soluble ICAM-1 was measured by enzyme immunoassay. Four acute phase proteins (C-reactive protein, acid alpha 1-glycoprotein, haptoglobin and ceruloplasmin) were estimated by immuno-nephelometry. No significant increase of soluble ICAM-1 could be demonstrated in the patients compared to a control group (median 273 ng/ml vs. 270 ng/ml). Furthermore, patients with advanced colorectal cancer did not demonstrate elevated soluble ICAM-1 compared to follow-up out-patients. Patients with present acute phase response as determined by C-reactive protein were shown to have increased soluble ICAM-1 compared to patients without acute phase reaction. Using other acute phase proteins no difference for soluble ICAM-1 has been shown. Our data suggest an association between acute phase response and increased ICAM-1 in patients with colorectal cancer which should be considered when the diagnostic and/or prognostic usefulness of soluble ICAM-1 is to be evaluated.