CYTOKINES AND TUMOR VACCINATION

Patients with locally advanced stages of renal cell carcinoma are at h igh risk of relapse or progress even after initial radical surgery. Ba sed on the proven efficacy of adoptive and active immunotherapeutic ap proaches of metastatic renal cell carcinoma, a phase II trial was star ted in 1989 using autologous, Newcastle disease virus modified and let hally irradiated tumor cell vaccines in combination with low-dose reco mbinant interleukin-2 (1.8 million U) and recombinant interferon-alpha 2a (1.0 million U) for a surgical adjuvant treatment. Patients were v accinated (subcutaneous injection) once a week for 8-10 weeks and the treatment was started about 4-10 weeks after surgery. Up to now more t han 208 patients with locally advanced renal cell carcinoma (stages pT 2-3a, N1-2, M0; pT3b-4, N0-2, M0) were vaccinated after initial radica l surgery (tumor nephrectomy with lymph node dissection and ipsilatera l adrenalectomy and if necessary in combination with en bloc removal o f venous extensions). We overview a follow-up of 203 evaluable patient s with a median disease-free survival of 21 months (range of 2-64 mont hs). During this observation period 18 relapses (8.9%) were diagnosed with 3 local relapses (1.5%), 10 lymph node metastases (5%) and/or dis tant organ metastases in 9 cases (4.5%). These progressive patients' d isease was treated by surgery and/or combined immunochemotherapy. Toxi city encountered on this tumor cell vaccination was mild (WHO grade 1) and was characterized by flu-like symptoms and fever up to 38.8 degre e Celsius for some hours beginning at 4 hours after the vaccine/cytoki ne application. Occasionally, a transient local inflammation at the si te of injection was observed. The comparison of the risk-factor-adapte d group of adjuvant treated renal cell carcinoma patients (locally adv anced stages) with historical data gave evidence for an improvement in disease-free survival on vaccination treatment. Although this was not a prospective randomized trial, we can summarize that the surgical ad juvant treatment of autologous tumor vaccines in combination with low- dose cytokines may improve relapse-free and overall survival in patien ts with locally advanced renal cell cancer.