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 cl inical remissions in metastatic renal cancer, but their benefit on sur vival times have not been demonstrated so far. The present analysis wa s designed to assess the effects of concomitant application of renal c ancer vaccine and cytokines on DTH skin responses to tumor cell challe nge, clinical remissions and patients survival. 40 patients with advan ced RCC, all with distant metastases in at least one organ, were enter ed after nephrectomy into a protocol involving multiple vaccinations w ith Newcastle disease virus (NDV)-infected autologous irradiated tumor cells, with subsequent repetitive 3 bi-weekly cycles of low dose inte rleukin-2 (r-IL-2) and interferon-alpha(2b)/rIFN-alpha(2) s.c. (1.5 mi llion 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 prov ed to be important for augmentation of DTH responsiveness upon tumor c ell 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 c omplete response (CR), 6 displayed a partial remission (PR), 12 showed stable disease (SD, median 25 months) and 17 tumor progression. Survi val distribution analysis predicted for all patients with stable disea se a median survival of 31 months while CR+PR patients had a median su rvival >4 years. 23/40 (57.5%) patients (CR, PR and SD) appear to have a significant survival advantage compared to the patients with progre ssive disease during the treatment period and to a historic reference group. Further data analysis revealed that the number of metastatic si tes was predictive of survival characteristics (p<0.05). A marked incr ease during 3 vaccinations of DTH anti-tumor reactivity predicted a su rvival advantage (35 vs 14 months), a correlation that was also signif icant by the Wilcoxon test. While the multi-modality treatment with au tologous tumor vaccine and s.c. administration of IL-2 and IFN-alpha a ppears to be effective in advanced RCC, a randomized trial (ASI-IL-2/I FN-alpha vs IL-2/IFN-alpha without ASI) is now set up to help assess t he role of ASI within the combined treatment regimen.