Study Suggests Higher Doses of Epoetin Alfa May Lengthen Time Between Injections

July 1, 2002

NASHVILLE-Interim results from a small pilot study suggest oncologists might be able to give epoetin alfa (Procrit) in a high-dose regimen that lengthens the time between injections once anemic patients reach maintenance levels of hemoglobin (ASCO abstract 1469).

NASHVILLE—Interim results from a small pilot study suggest oncologists might be able to give epoetin alfa (Procrit) in a high-dose regimen that lengthens the time between injections once anemic patients reach maintenance levels of hemoglobin (ASCO abstract 1469).

The experimental regimen begins with weekly injections of 60,000 units, and can switch to 120,000 units administered every 3 weeks after a patient’s hemoglobin level rises 2 g/dL or more above baseline. Lead investigator Jeffrey Patton, MD, of Tennesee Oncology in Nashville reported that 11 of 20 chemotherapy patients in the trial have reached the threshold for entering the maintenance phase and so far are sustaining their hemoglobin levels with the less frequent injections.

Epoetin alfa is usually given in weekly 40,000 units that can go up to 60,000 units if hemoglobin levels do not respond. It is approved for use in anemic cancer patients receiving chemotherapy for nonmyeloid malignancies.

Threshold for Raising Dose

Previous investigations have established that weekly doses of epoetin alfa produce benefits similar to doses given three times a week. Dr. Patton said front-loading epoetin alfa with a high initial dose has been looked at but not in large numbers of cancer patients. "To my knowledge this has not been done in a chemotherapy-induced setting," he said.

All 20 patients in the nonrandomized pilot study had hemoglobin levels of 11 g/dL or less, and were receiving chemotherapy for a nonmyeloid malignancy. Patients who had been treated with epoetin alfa or any investigational form of erythropoietin were excluded.

Everyone started on the 60,000-unit dose. Although this is 50% higher than the standard dose of epoetin alfa, Dr. Patton said that it is not uncommon, as about one-quarter of patients receiving the standard dose end up being raised to 60,000 units. The study protocol allows patients to move to the 120,000-unit maintenance schedule after 8 weeks, providing their hemoglobin counts have met the threshold for improvement. Seven of the 11 patients on maintenance therapy reached the threshold at 9 weeks.

Criteria for Lowering Dose

The protocol also includes criteria for lowering the dose if a patient’s hemoglobin levels rise too rapidly. Treatment stops completely if hemoglobin exceeds 15 g/dL. It resumes if the level falls back down to 13 g/dL, but the dose is reduced by 20,000 units (to 40,000 or 100,000 units, depending on whether the patient was receiving a loading dose or a maintenance dose). The 20,000-unit dose reduction also goes into effect if a patient’s hemoglobin rises by more than 1.3 g/dL in a 2-week period.

Seven patients had reductions because their hemoglobin rose too rapidly during the loading phase. Six patients had adverse events, though none were related to epoetin alfa. Three deaths were recorded, but these also were not related to the therapy. Dr. Patton and his colleagues did not evaluate transfusions in the interim analysis.

The investigators concluded that although the data analysis is not complete, results so far show a trend toward marked increases in hemoglobin in the initial phase of the regimens and little change in the boosted hemoglobin levels during the maintenance period. When the study is completed, the final data will be analyzed to determine if larger-scale studies are warranted using the same dosing regimen.

‘‘Every 3 week dosing appears to maintain hemoglobin levels similar to every week dosing,’’ Dr. Patton said.