Two studies presented at the 2007 Gastrointestinal Cancer Symposium, sponsored by the American Society of Clinical Oncology (ASCO), the American Gastroenterological Association (AGA), the American Society for Therapeutic Radiology and Oncology (ASTRO), and the Society of Surgical Oncology (SSO),  suggest that darbepoetin alfa (Aranesp®) and epoetin alfa (Procrit®) can be given less frequently than the once weekly schedule and maintain effectiveness. Data presented support the use of an extended dose schedule of either darbepoetin alfa  Q3W or Q2W, or epoetin alfa Q2W for correction of chemotherapy induced anemia in patients with gastrointestinal cancers.

Both epoetin alfa and darbepoetin alfa  are used to treat chemotherapy induced anemia. Both are usually given on a weekly basis but one year ago darbepoetin alfa  was approved by the FDA for administration every 3 weeks, which makes administration more convenient and can be timed more easily with chemotherapy administration. There has been very little data generated on correction of chemotherapy induced anemia in patients with gastrointestinal cancers.

Researchers involved in a multi-center trial evaluated the administration of epoetin alfa at a dose of 80,000 U every 2 weeks or 40,000 U weekly in 310 patients with solid cancers.[1] Patients received epoetin alfa for hemoglobin levels <11 g/dL, the dose was reduced for a hemoglobin level > 12 g/dL and withheld for hemoglobin levels >12 g/dL. The study period was 13 months. Approximately half the patients in this trial received dose-dense chemotherapy. This report dealt with a retrospective analysis of 42 patients with colorectal cancer. Twenty-four patients were randomly allocated to receive epoetin alfa every 2 weeks and 18 were allocated to receive weekly epoetin alfa. These researchers made the following observations:

• Mean hemoglobin change from base-line was +1.29 for Q 2 week schedule and 1.24 for the q week schedule.
• Median time to achieve a hemoglobin of 11 g/dL was 15 days for the Q 2 week schedule and 36 days for the Q week schedule.
• No patient in the Q 2 week group received transfusions vs 14% in the Q week group.
• There were no deaths in the Q 2 week group vs 3 in the Q week group none of which were attributable to epoetin alfa.
• Dose adjustments were less frequent in the Q 2 week group.

These authors concluded that the 80,000 U Q 2 week schedule was safe and effective in patients with colorectal cancer.

The second study was an open label phase II study which randomly allocates patients to receive weekly, every 2 week or every 3 week darbepoetin alfa to correct chemotherapy induced anemia in patients with cancer.[2] Patients in the weekly group received an initial dose of 300 mcg of darbepoetin alfa  with a maintenance dose of 200 mcg. Patients in the Q 2 week group received an initial 300 mcg darbepoetin alfa dose with a maintenance dose of 200 mcg. Patients in the Q 3 week group received a 500 mcg initial dose of darbepoetin alfa  with a maintenance dose of 300 mcg. The expected accrual to this study is 750 patients. The current study was an interim analysis of 487 patients, 111 of whom had gastrointestinal tumors. The study treatment period was 25 weeks but data presented represented only 13 weeks of treatment. Data on the administration of darbepoetin alfa every 2 or 3 weeks were combined and compared to the weekly dosing. The mean increase in hemoglobin was 0.9-1.1 for all groups. Approximately 65-70% of patients achieved a target hemoglobin level of 11 grams with no difference between groups. Treatment related adverse events were similar for all groups. There were not major differences in results between gastrointestinal tumors and non-gastrointestinal tumors. These authors concluded that darbepoetin alfa could be given on a 2 or 3 week basis to coincide with the administration of chemotherapy.

These data further support the use of an extended dose schedule of either darbepoetin alfa  or epoetin alfa for correction of chemotherapy induced anemia in patients with gastrointestinal cancers.

To successfully complete this CME activity, please read the additional 2 articles from the 2007 ASCO GI Symposium before you take the post test:

ASCO GI 2007: Updates in the Treatment of Colorectal Cancer

Allyson Ocean, MD, Weill Medical College, Cornell University

ASCO GI 2007: Patient Communication and Expectations
Allyson Ocean, MD, Weill Medical College, Cornell University

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