Abstract
CT-associated cognitive dysfunction, which frequently manifests as subtle changes in memory, concentration, and ability to remain focused or organized, can adversely affect cancer pts’ QOL. EPOLYM, a prospective, international, multicenter, open-label, phase IIIb trial has been conducted to investigate the efficacy, safety, and clinical outcomes, including effect on cognitive function, of epoetin alfa 40,000 IU sc QW in anemic (Hb <12 g/dL) pts with hematologic malignancies. Pts enrolled had either non-Hodgkin’s lymphoma, multiple myeloma, Hodgkin’s disease, or chronic lymphocytic leukemia, for which they were receiving or were expected to receive CT (planned N = 1,000). Dosage increases or decreases were to be made based on clinical response (target Hb, 11.5–13.0 g/dL). Cognitive function was evaluated from baseline to Week 24 (or last evaluation) using the Cognitive Drug Research Computerised Cognitive Assessment System, patient-completed, computer-scored tasks of attention (Simple Reaction Time, Choice Reaction Time, Digit Vigilance), working memory (Numeric Working Memory), and secondary memory (Immediate and Delayed Word Recognition, Picture Recognition). To further characterize the data, task scores were variously summed to provide 4 factor scores (and aspects of cognitive function measured): Power of Attention (concentration intensity), Continuity of Attention (ability to sustain concentration), Quality of Memory (amount of information that can be stored and successfully retrieved in working and long-term memory), and Speed of Memory (speed in ability to recognize information previously presented or held in working memory). Changes from baseline in Hb levels and transfusion requirements were determined and QOL was assessed using the Functional Assessment of Cancer Therapy-Anemia Subscale and the Linear Analog Scale Assessment. Because of the apparent relationship between affect and cognition, anxiety and depression were evaluated at the time of cognitive assessment using the Hospital Anxiety and Depression Scale (HADS). Transfusion, QOL, and HADS results are not considered here. The cognitive data for 568 pts who had completed up to 24 weeks of therapy were examined in an interim analysis. Results showed that Power of Attention was slightly impaired and Continuity of Attention was slightly improved over the course of the study; however, these effects were small and unlikely to have everyday behavioral significance. Greater changes were observed in regard to memory. Mean Speed of Memory was decreased 358.9 msec by Week 24, representing an 8% improvement from baseline. Also, improvement was noted in Quality of Memory, with the score for this factor increased by 0.0899 at Week 24 from a baseline value of 2.895. The improvement in cognitive function was associated with an increase in Hb from 10.5 g/dL at baseline to about 12 g/dL beginning at Weeks 8 to 12 and sustained for up to 24 weeks. Results of this interim analysis suggest improvement in several aspects of cognitive function associated with increased Hb levels in anemic CT pts with hematologic malignancies. These results will have to be confirmed by findings based on the full study cohort.
