Tumor infiltrating lymphocytes and continuous infusion interleukin-2 aftermetastasectomy in 61 patients with melanoma, colorectal and renal carcinoma

Aims and background: Adoptive immunotherapy with tumor infiltrating lymphoc yte (TIL) reinfusion plus continuous interleukin-2 (IL-2) infusion could re present an innovative way of treating immunogenic tumors. This study theref ore recruited melanoma, colorectal and renal carcinoma patients whose metas tases had been surgically removed. Study design: The treatment was initially given to 22 patients with advance d disease and more recently to 39 disease-free (DF) patients after radical metastasectomy. The latter group was selected in view of a theoretically be tter lymphocyte/tumor cell ratio and with the aim to improve disease-free a nd overall survival (DFS-OS) in very high risk patients. The starting IL-2 dose was 12 MIU/day (West's schedule); doses were modulated on the bases of toxicity parameters. Even though patients received different total amounts of IL-2, all of them completed the treatment. Results: The treatment was offered to 22 advanced-stage cancer patients (12 melanomas, 9 colorectal carcinomas, 1 kidney carcinoma). Few and short sta bilizations were observed with a median survival of 12 months (range, 3-29) , Subsequently, another 39 patients were treated in an adjuvant setting aft er radical metastasectomy (18 melanomas, 19 colorectal carcinomas, 2 kidney cancers). Eleven out of 17 DF melanoma patients (64.7%) are still free of disease after a median of 37+ months (range, 5+ - 69+), In the group of DF colorectal cancer patients eight (44.4%) are still DF after a median of 21 months (range, 7+ - 67+ months). One of the two patients with kidney cance r is still DF after 28+ months. Two patients (1 melanoma and 1 colorectal c ancer) had just been treated and were therefore not evaluable. Severe toxic ity occurred in three cases but was rapidly resolved. There was a great div ersity in IL-2 doses administered; comparison of the total IL-2 dose admini stered between the patients who are still DF and those who progressed revea led no difference between the two groups of colorectal cancer patients, whe reas meianoma patients who progressed received an average IL-2 dose of 6.5 MIU/day versus 15.8 MIU/day in DF patients. No differences were observed In any of the groups between the number of TILs reinfused and clinical respon se. Conclusions: The study is still ongoing; it has been decided to focus on DF melanoma patients after radical metastasectomy, for whom the data seem to be encouraging. Further endpoints of the study are the role of IL-2 dosage in the adjuvant setting, and the possibility to make correlations between b iological parameters and clinical results.