Late mortality and levamisole adjuvant therapy in colorectal cancer.

Beginning in 1975, 78 patients with resected stage B and C colorectal carcinoma were randomly assigned (2:1) to receive either levamisole 2.5 mg kg-1 day-1 given for 2 days every week for 18 months or placebo therapy in the same schedule. Pretreatment characteristics (age, gender, disease site, CEA and stage) and the pattern of follow-up were similar in both groups. For the first 5 years following randomisation, relapse-free survival and overall survival were similar in the two treatment groups. Subsequently, excess late mortality was associated with levamisole group assignment. Consequently, overall survival was somewhat greater in the placebo group than in the levamisole group, 68% vs 38% (P < 0.08). For patients surviving 5 years from randomisation, subsequent survival favoured placebo over levamisole (100% vs 57%; P < 0.03). The absolute numbers of deaths were 27 in the levamisole group (19 definitely cancer related) and seven in the group placebo (five definitely cancer related). This long-term result seen with a more intensive adjuvant levamisole dose and schedule suggests: (1) other levamisole adjuvant trials in patients with colorectal cancer should be examined for long-term outcome; (2) future trials utilising the even higher levamisole dosage required for clinical immunomodulation should proceed cautiously.