Tumor response and 4 year survival-data of patients with advanced renal-cell carcinoma treated with autologous tumor vaccine and subcutaneous R-IL-2 and IFN-alpha(2b).

Several forms of immunotherapy are apparently effective in inducing clinical remissions in metastatic renal cancer, but their benefit on survival times have not been demonstrated so far. The present analysis was designed to assess the effects of concomitant application of renal cancer vaccine and cytokines on DTH skin responses to tumor cell challenge, clinical remissions and patients survival. 40 patients with advanced RCC, all with distant metastases in at least one organ, were entered after nephrectomy into a protocol involving multiple vaccinations with Newcastle disease virus (NDV)-infected autologous irradiated tumor cells, with subsequent repetitive 3 bi-weekly cycles of low dose interleukin-2 (r-IL-2) and interferon-alpha(2b)/rIFN-alpha(2) s.c. (1.5 million r-IL-2 Cetus units/m(2)/day and 3 million IFN-alpha IU/m(2)/day). In a pilot study the coadministration of a supplement of r-IL-2 proved to be important for augmentation of DTH responsiveness upon tumor cell challenge. Patients with aneuploid tumors vaccinated without r-IL-2 apparently developed an anergy to the vaccine throughout vaccination. In the main study, of the 40 evaluable RCC patients, 5 exhibited a complete response (CR), 6 displayed a partial remission (PR), 12 showed stable disease (SD, median 25 months) and 17 tumor progression. Survival distribution analysis predicted for all patients with stable disease a median survival of 31 months while CR+PR patients had a median survival >4 years. 23/40 (57.5%) patients (CR, PR and SD) appear to have a significant survival advantage compared to the patients with progressive disease during the treatment period and to a historic reference group. Further data analysis revealed that the number of metastatic sites was predictive of survival characteristics (p<0.05). A marked increase during 3 vaccinations of DTH anti-tumor reactivity predicted a survival advantage (35 vs 14 months), a correlation that was also significant by the Wilcoxon test. While the multi-modality treatment with autologous tumor vaccine and s.c. administration of IL-2 and IFN-alpha appears to be effective in advanced RCC, a randomized trial (ASI-IL-2/IFN-alpha vs IL-2/IFN-alpha without ASI) is now set up to help assess the role of ASI within the combined treatment regimen.