Effects of Darbepoetin Alfa Administered Once Per Cycle for the Prevention of Anemia on the Incidence of Transfusions, Neurocognitive Functions, and Symptom Assessment.

Background: Chemo-naïve sarcoma patients (pts) experience severe anemia during front-line chemotherapy (CT) with doxorubicin and ifosfamide (AI). In our prior study with AI, vast majority of pts (65 of 68, 93%) who received >1 cycle of CT, required PRBC transfusions. Anemia has significant negative impact on pts quality of life (QOL) and neurocognitive (NC) functions. Prior studies have shown that cancer pts receiving CT experience decline in NC functions and QOL. Preclinical studies suggest that treatment with erythropoietic stimulating agents (ESA) may protect NC functions. The purpose of the present study was to evaluate the effects darbepoetin alfa (DA) administered once per cycle as prophylaxis on the prevention of anemia, need for transfusions, symptom burden and NC functions in sarcoma pts receiving AI.

Methods: DA (initial dose 500 mcg SC) was administered once per cycle before CT (day 0) starting from cycle-1(n=26) or cycle 2 (n=23) and continued up to max 6 cycles. Pts underwent a complete battery of neuropsychological tests and assessment of symptoms via the MD Anderson Symptom Inventory (MDASI) and quality of life with the Functional Assessment of Cancer Therapy-Anemia (FACT-An) Scale at baseline, during CT (after 3 cycles) and at the end of study. At baseline, the median hemoglobin (Hb) was 13.2 g/dL, and only 5 of 49 pts were anemic to a level <11 g/dL. However, significantly more NC deficits or symptoms, including memory loss (29% of pts), fatigue (24%), pain (21%), distress (16%), and sadness (16%) were seen in pts at baseline as compared to normal populations. Pts with higher baseline Hb values had significantly less sadness (p=0.008) and less shortness of breath (p=0.003). Of the 45 pts that received > 1 cycle of CT (median, 4; range, 2–6 cycles), 38% avoided PRBC transfusions. Patients who avoided transfusions had less distress (p=0.032) and less sadness (p=0.01) during treatment. Patients with higher Hb nadir during treatment had less numbness and tingling (p=0.006). Overall, there was a significant decline in verbal fluency, non-dominant hand dexterity (p<0.001), and memory recall (p=0.018). Interestingly, there was a significant improvement in several symptoms including distress (p=0.001), sadness (p=0.032), and pain (p=0.004) during treatment as compared to baseline. These findings suggest that cancer pts can have NC deficits prior to CT. Prevention or early intervention with ESA may avoid the need for transfusions, reduce symptom burden and NC deficit.