Interleukin-2 (Il-2) Chrono-Infusion (Chi) In Metastatic Renal Cell Carcinoma (Mrcc): A Phase I/Ii Study.

423 Background: The soprachiasmatic nucleus represents the pacemaker coordinating circadian rhythm. Its dysregulation in neoplastic patients (pts) can be an important inducer/promoter of cancer progression. It is a potential mediator of cancer immunosuppressive effect and quality of life (QoL) impairment. CHI allows concentration of time active treatment with possible impact on QoL and immune and hormone set-up. Aim of this study was to evaluate feasibility, dose limiting toxicity and activity of CHI IL-2 in mRCC.22 pts were enrolled, 14 were naive and 8 pretreated (chemo/immunotherapy in 6 and targeted in 6). M/F ratio was 16/6, median age 68 y. IL-2 CHI was administered iv in 8 h (peak 1 am, 9 am, 5 pm) from 2 MUI/m2 with escalated dose ( Fibonacci scale) x 3 days/q 2 wks for 4 cycles. Four maintenance cycles were performed in responsive/stable pts.from January 2005 to July 2009, out of 22 pts, 3 were treated onto each Le (I-V ) and 7 in the VI. G3-4 toxicity was reported in four pts (hypotension in 2, renal in 2 and diarrhoea in 1) on the VI Le ( DLT 18,6 MUI/m2).1 CR, 2 PR, 9 SD, 10 PD. ORR was 25%%. DCR on overall/ good-intermediate group (MSKCC) was 54%/69%. Median PFS and OS were 4,5 and 14,5 mos respectively. In a univariate analysis dose Le (4-6 vs. 1-3), PS (0 vs 1-2), gender (M vs F) and cD3, cD4, cD8 count (gain vs drop) were statistically significant for OS. In a univariate analysis age (< 65 y vs. >65y), Motzer score (0-1-2 vs 3) increase/reduction of cD19, cD16, HLA-DR, cD4/cD8, increase/reduction of prolactine, reduction/increase of ACTH-Cortisol showed a trend of survival improvement.IL-2 CHI aappeared safe in a standard care unit, moderately toxic and active in mRCC. Phase 2 study with dose Le V is now ongoing.