Prospective randomized reappraisal of 5‐fluorouracil in metastatic colorectal carcinoma a comparative trial with 6‐thioguanine

In order to redefine the effectiveness of 5‐fluorouracil (5‐FU) as palliative therapy in patients with metastatic colorectal carcinoma, and to compare the effectiveness of 6‐thioguanine (6‐TG) with that of 5‐FU, we studied 176 patients with metastatic colorectal carcinoma in a randomized prospective trial (SEG 79GI268). The pretreatment performance status of all patients was greater than 50% (ambulatory), and there was an equal distribution of patients with favorable pretreatment characteristics into each of the treatment regimens. Complete responses were only seen to 5‐FU, but were obtained in only 3% of instances. The overall complete plus partial response rates were not different for 5‐FU (8%) versus 6‐TG (3%), or for patients who had shown prior progression on chemotherapy and who then received 6‐TG in a nonrandomized fashion (7%). The time to tumor progression on each of the treatment programs was similar, 1.0 months. Survival was also similar in each regimen in the randomized study (6.3 months for 5‐FU versus 7.9 months for 6‐TG). However, survival was only 4.8 months for patients with previously drug‐resistant tumors treated with 6‐TG in the nonrandomized arm. in 16 patients failing 6‐TG who then received 5‐FU, there were no objective responses. Similarly, in patients failing 5‐FU on this study who then received 6‐TG, there were no responses in nine patients. Dose‐limiting toxicity was observed in 40% to 51% of patients, and consisted of myelosuppression, vomiting, or diarrhea. It is concluded that 5‐FU is a minimally effective agent in a very small number of patients with metastatic colorectal carcinoma. The drug 6‐TG is equally ineffective in this setting. Alternative treatment programs to the systemic use of 5‐FU should be considered in patients requiring palliative chemotherapy.