Elevated interleukin-6 levels correlation with anemia, symptom burden, and neurocognitive deficit in cancer patients receiving chemotherapy: Effects of darbepoetin-alfa administered once per cycle for prevention of anemia

Abstract

19505 Background: Chemo-naïve sarcoma pts experience severe anemia during chemotherapy (CT) with adriamycin and ifosfamide (AI) resulting in PRBC transfusions (Tx) in >90% of pts. Anemia has a negative impact on quality of life (QOL) and neurocognitive (NC) functions (fx). Preclinical studies suggest that treatment with erythropoietic stimulating agent (ESA) may protect NC fx. The purpose of this study was to evaluate the effects of darbepoetin (Initial dose 500mcg) administered once per cycle on prevention of anemia, transfusions, symptom burden and NC fx. Methods: Pts underwent assessment for neuropsychological tests, symptoms (MDASI), and quality of life (QOL). To determine if NC deficits and Hb were correlated to cytokine levels, serum IL-1, IL-6, and TNF were measured at baseline, after 3 cycles and completion. Results: Baseline median hemoglobin (Hb) was 13.2 g/dL (n=49); however, significantly more NC deficits and symptoms were seen in pts as compared to normal. Interestingly, serum IL-6 levels were significantly elevated as compared to normal at baseline and during treatment (p<0.001), and were negatively correlated with baseline Hb (p=0.003) and significantly associated with NC deficits, QOL and symptoms. Of 45 pts that received > 1 cycle of CT, 38% avoided PRBC Tx. Pts with higher baseline Hb had less sadness and shortness of breath (p<0.01). Pts with higher Hb nadir had lower tingling/numbness (p=0.006). Pts who avoided transfusions had less distress (p=0.032), less sadness (p=0.01), and better motor fx (p=0.005). Conclusions: These findings suggest that cancer pts can have NC deficits prior to CT. Prevention/early intervention with ESA may avoid transfusions, reduce symptom burden, and NC deficit. Significant correlation of anemia, symptoms, and NC deficit with elevated IL-6 levels suggest that anti-IL-6 treatment may improve response to ESA and NC functions. [Table: see text] No significant financial relationships to disclose.