The Pharmacokinetics of Darbopoetin Alpha Administered Subcutaneously in Patients with Non-Myeloid Malignancies Receiving Multicycle Chemotherapy

Reviewer: Walter F. Sall, MD
The Abramson Cancer Center of the University of Pennsylvania
Last Modified: December 9, 2001

Presenter: A. C. Heatherington
Presenter's Affiliation: Amgen, Inc.
Type of Session: Poster

Background

Darbopoetin Alpha (NESP, Aranesp) is a novel synthetic variant of rHuEPO possesing 2 additional consensus N-linked carbohydrate groups.

Darbopoetin alpha has been shown to have a 2-3 fold increased half life compared to rHuEPO in patients with chronic renal insufficiency. Serum half life is also longer in cancer patients receiving chemotherapy.

Darbopoetin alpha has been shown to increase hgb levels when dosed as infrequently as every three weeks.

This study analyzes the pharmacokinetics of darbopoetin alpha in cancer patients receiving multi-agent chemotherapy receiving single and multiple 2.75 ug/kg weekly doses.

Materials and Methods

Darbopoetin alpha was dosed weekly at 2.25 ug/kg. Chemotherapy was given on three week cycles beginning the same day as the first injection of darbopoetin alpha.

Eligibility: hgb less than or equal to 13 non-myeloid leukemia ECOG 0-2 no rHuEPO within 8 weeks.

29 patients enrolled. Mean baseline hgb was 9.8. 21 solid tumors, 8 lymphoproliferative cancers.

Weekly trough serum samples were analyzed prior to each subsequent darbopoetin alpha injection.

Serum Darbopoetin alpha levels were measured using ELISA. Endogenous EPO levels were also measured.

Results

Absorption of darbopoetin alpha following SC injection was slow. Mean time to peak serum concentration following a single SC injection was 72 hours.

Darbopoetin alpha did not accumulate to unacceptably high levels following multiple weekly doses.

Trough levels tripled between the first and second week. Trough levels plateaued and were consistently stable in subsequent weeks.

Endogenous EPO levels followed the same patterns as weekly injected Daarbopoetin alpha with a four fold increase in serum levels in the first week of chemo followed by a plateau.

Author's Conclusions

Slow absorption of SC injected darbopoetin alpha results in prolonged serum half life. Less frequent dosing patterns can therefore be used.

There is no accumulation of darbopoetin alpha following multiple sequential weekly doses.

Consistent and reproducible trough patterns are seen from one chemotherapy cycle to the next.

Endogenous EPO follows the same serum concentration pattern as weekly injected darbopoetin during chemotherapy treatment.

Clinical/Scientific Implications
This study supports the use of weekly injected darbopoetin alpha as a safe and effective alternative to more frequent dosing of rHuEPO. SC injection of darbopoetin alpha acts as a depot injection, providing consistent serum levels of the drug without accumulating to supra-therapeutic levels. Better patient compliance and simplification of chemotherapy treatment regimens will hopefully result from the use of this drug.

Oncolink's ASH Coverage made possible by an unrestricted Educational Grant from Amgen^®.