HOSPITAL PRACTICE

NCCN updates guidelines for chemo-induced anemia

After deliberating for months, a panel of specialists from the National Comprehensive Cancer Network (NCCN) recently released updated practice guidelines for treating chemotherapy-induced anemia in patients with nonmyeloid malignancies.

Now that there are two Food & Drug Administration-approved erythropoietic agents to choose from—epoetin alfa (Procrit, OrthoBiotech), approved in 1991; and darbepoetin alfa (Aranesp, Amgen), cleared for market last July—the new guidelines suggest that either compound can do the job when treatment is indicated.

"These guidelines are a consensus statement of the authors regarding their views of currently accepted approaches to treatment," NCCN says in its introduction. It urges clinicians and pharmacists to carefully read the pertinent studies (referenced in the guidelines) and use the data to help develop regimens based on patients' needs. "Any clinician seeking to apply or consult these guidelines is expected to use independent medical judgment in the context of individual clinical circumstances to determine any patient's care or treatment."

In studies of patients with chemotherapy-related anemia, both agents have shown similar activity, e.g., an average rise of 2 g/dL from baseline hemoglobin levels over a 12-week period, which headed off transfusion in about 60% of treated patients.

Optimal dosing regimens for Procrit and Aranesp have not yet been determined, however. According to the guidelines, an important goal of ongoing clinical trials "will be to define the optimal regimen.... Hopefully, less frequent dosing regimens with equal efficacy will result."

Here are some of the NCCN recommendations for patients who have developed or are developing clinically significant chemotherapy-induced anemia:

• Initiate treatment when patients' hemoglobin levels are under or equal to 11 g/dL. This differs from usual practice, which calls for therapy to begin at approximately 10.1 g/ dL.

• Treat with epoetin alfa 40,000 units weekly or 10,000 U three times a week by subcutaneous injection, or darbepoetin 2.25 mcg/kg weekly by subcutaneous injection (oral iron supplementation as indicated).

• If there is an initial response of a hemoglobin increase by 1g/dL, titrate dosage to maintain optimal hemoglobin of 12 g/dL; if there is no response at four weeks for epoetin or six weeks for darbepoetin, increase dose of epoetin to 60,000 U weekly or 20,000 U t.i.w. by subcutaneous injection, or increase darbepoetin up to 4.5 mcg/kg weekly by subcutaneous injection.

• If there is still no hemoglobin response, discontinue erythropoietin and transfuse as indicated based on institutional guidelines.

The FDA recommends the same regimen.

The authors explain that they revised the usual practice of initiating erythropoietic therapy at hemoglobin levels of 10.1 g/dL to earlier levels of 11g/dL (the level that was previously used to initiate therapy) because recent data from 4,382 patients showed that the largest quality-of-life improvements for each 1g/dL increment in hemoglobin increase occurred when the hemoglobin rose from 11.0 to 12.0 g/dL. This suggests that moving hemoglobin into the 11g/dL-12g/dL range may greatly improve patients' quality of life.

Rebecca B. Arbuckle, director of pharmacoeconomics, division of pharmacy, M. D. Anderson Cancer Center, agreed. "Evidence supports [the concept] that the most benefit to patient quality of life and function occurs with the 1-gm change from 11 to 12g/dL. Therefore, beginning therapy sooner may improve the quality of life and protect the value from going lower.

"The NCCN guidelines for use of erythropoietic growth factors are generally similar to the guidelines established here [several years ago]," she continued. "The addition of Aranesp to the formulary initiated a review of our guidelines. Thus, our Growth Factor Task Force reviewed the literature and other data important to the use of the new product. We determined that, for these products, the recommended dosing of epoetin alfa would remain at 40,000 units per week, and the recommended dose of darbepoetin alfa could be no higher than 200 mcg given every other week—increased to 300 mcg in nonresponders—to maintain cost-effective treatment, under current cost and reimbursement guidelines."

Naomi Pfeiffer

The author is a clinical writer based in New York.

Naomi PFEIFFER. NCCN updates guidelines for chemo-induced anemia.

Drug Topics

Jun. 2, 2003;147:41.