Actieve specifieke immunotherapie als adjuvante behandeling van patienten met coloncarcinoom in stadium II of III; prospectief gerandomiseerd onderzoek

Objective. To determine the clinical effect of adjuvant active specific immunotherapy (ASI) with tumour cells and BCG after radical surgery in stage II and stage III colon cancer patients. Design. Prospective randomized controlled clinical trial. Method. In the period 1987-1996, 254 patients were randomly assigned postoperatively in the Free University Hospital in Amsterdam and in II participating hospitals in the Netherlands to receive either ASI or no adjuvant therapy. ASI consisted of 4 intradermal vaccinations with 10⁷ irradiated autologous turnout cells. Treatment started 4-5 weeks after operation with 3 vaccinations, at one-week intervals followed by the fourth vaccination 6 months after operation. The first two vaccinations also contained 10⁷ BCG organisms. Patients were followed for time to recurrence, recurrence-free and overall survival. Analysis was done on the basis of randomization. Results. At 5.8 year median follow-up a significant improvement (p = 0.016; relative risk reduction: 43% (SD: 18)) in the recurrence-free interval in all patients given ASI was seen; there were 44 recurrences in the control group and 27 in the ASI group. Analysis by stage showed no significant benefit of ASI in stage III disease. The major impact of ASI was seen in patients with stage II disease, with a significant improvement in recurrence-free interval (p = 0.013) and a 57% (SD: 23) relative reduction in risk of recurrences. This was accompanied by a significant improvement in recurrence-free survival (p = 0.043; 42% relative risk reduction (SD: 21)) and an improvement of disease-specific survival (p = 0.061). Apart from transient ulcers at the first two vaccination sites and fever/chills after vaccination no adverse events were observed. Conclusion. ASI had a significant clinical benefit in colon cancer patients with stage II disease. ASI caused minimal adverse reactions and should be considered as a treatment for these patients.