NEW YORKSynchronized every-3-week delivery of myelosuppressive chemotherapy and an erythropoiesis-stimulating protein (ESP) to prevent chemotherapy-induced anemia is convenient for patients and feasible using darbepoetin alfa(Drug information on darbepoetin alfa) (Aranesp), but researchers have worried that it could affect efficacy and safety, since myelosuppressive chemotherapy is known to be associated with a rapid and transient increase in circulating erythropoietin(Drug information on erythropoietin) levels.
At the Chemotherapy Foundation Symposium XXIV, John Glaspy, MD, professor of medicine, UCLA, presented results showing no significant difference in response in groups randomized to receive chemotherapy and darbepoetin on the same day every 3 weeks or darbepoetin, 6.75 μg/kg one week prior to chemotherapy. The results were previously published in the European Journal of Cancer (41:1140-1149, 2005).
As had been observed previously, a single dose of chemotherapy was associated with a mean fourfold increase in endogenous erythropoietin levels lasting about 1 week. The investigators also found that the pharmacokinetics of darbepoetin differed by treatment schedule. "It appears that chemotherapy stops the clearance of darbepoetin alfa, and levels remain higher than in the asynchronous group," Dr. Glaspy said, suggesting that synchronous dosing may have some pharmacokinetic advantages. He also noted that in this study of chemotherapy patients, the measured half-life of darbepoetin was approximately three times longer than the published half-lives recorded in dialysis patients (24 hours).
For both groups, he said, there was a clear increase in mean hemoglobin over time, and there was no significant difference between groups in the magnitude of response over the 6 weeks of the study.
The hemoglobin response kinetics were different in the two groups: In the asynchronous patients, hemoglobin rose relatively rapidly for a week after administration of darbepoetin until they received chemotherapy. They then had no further response until they received their next darbepoetin dose. In the synchronous group, there was no hemoglobin response for a week, followed by a dramatic rise that continued until the next round of chemotherapy. "These two curves wrap around each other, and they wind up crossing the finish line at about the same time," he said.