Adjuvant chemotherapy with 5-fluorouracil and folinic acid in colorectal cancer: Evaluation of toxicity

Background: Adjuvant chemo- and radiotherapy for colorectal carcinoma has been established during recent years. Currently treatment with 5-fluorouracil (5-FU) and levamisole (LEV) treatment for Dukes C colon cancer; for rectal cancer (Dukes B2-C) radiation and 5-FU single-agent chemotherapy is considered treatment of choice. Progress for therapy is expected by the introduction of folinic acid (FA) and 5-FU as chemotherapy. However, there has been concern about increased toxicity; therefore the object of this report is to present toxicity data from two ongoing adjuvant treatment trials on colorectal cancer. Method: In the study for colon cancer (Dukes C), 3 treatment groups were compared: arm A (5-FU/LEV, weekly, 12 months), arm B (5-FU/FA, days 1-5, every 4 weeks, 12 cycles) and arm C (like B, 6 cycles). In the rectal cancer study (Dukes B2-C) arm A (5-FU/FA, days 1-5, every 4 weeks, 12 cycles) and arm B (like A, 6 cycles) were compared. During the second cycle radiation up to 50.4 Gy was performed and chemotherapy was applied weekly. Results: From 1993 until December, 1994 a total of 146 patients were recruited in both studies. Data from 92 completely documented patients, who received adjuvant treatment either with 5-FU+FA (n=76) or 5-FU+LEV (n=16), could be analysed for toxicity patterns. In the group with 5-FU+LEV one case with WHO grade-IV toxicity (haematological, gastrointestinal) and 6 events with grade-ill toxicity occurred (CNS, alopecia, fever). In the 5-FU+FA group 15 events with grade-III toxicity were found, most of these gastrointestinal, and one case of cardiotoxicity All patients recovered, and treatment-related death was not seen. Conclusion: For the majority of patients therapy was tolerable. Preliminary data of our two adjuvant trials in colon and rectum carcinoma using chemotherapy or radio-chemotherapy suggest that treatment with 5-FU+LEV and 5-FU+FA is safe but has to be performed under adequate control and dose adjustment.