Darbepoetin

Epoetin treatment has also been found to improve QOL in cancer patients. In a randomized study of 180 patients with anemia due to hormone-refractory prostate cancer, Johansson and colleagues observed that epoetin therapy improved QOL, physical functioning, and fatigue in many of the treated patients.33 Quirt and colleagues found that, regardless of whether patients were receiving chemotherapy, Hb levels increased with administration of epoetin, and these increases were positively correlated with improved QOL.32 Glaspy and colleagues reported that mean energy level increased by 38%, activity increased by 32%, and overall QOL increased by 24% in over 1,000 patients with nonmyeloid malignancies who received 4 months of epoetin therapy while undergoing chemotherapy. In their controlled study of 375 patients receiving nonplatinum chemotherapy, Littlewood and colleagues determined that compared with those receiving placebo, the patients treated with epoetin showed increased Hb levels (P <0.001) and improvement in a number of QOL domains, including energy level, fatigue, and ability to perform daily activities (P <0.01).30 Similarly, Demetri and associates reported that Hb values increased and were associated with improved activity level, energy, and overall well-being in patients receiving epoetin therapy.

Treatment of anemia may also improve response to treatment. Frommhold and colleagues, in a study of nearly 900 head and neck cancer patients, found that anemic patients treated with epoetin and undergoing radiotherapy experienced better locoregional tumor control than patients not receiving epoetin.36 Similarly, Glaser and colleagues have noted improved response to chemoradiation for oral or oropharyngeal squamous cell carcinoma when patients are treated with epoetin.37,38 A Phase III trial is currently being conducted by the Gynecologic Oncology Group to evaluate the efficacy of maintaining Hb levels above 12 g/dL with erythropoietin versus above 10 g/dL without erythropoietin in anemic patients receiving concurrent radiation and cisplatin for cervical cancer.39 The Radiation Oncology Therapy Group is also conducting a randomized Phase III trial, assessing the effect of erythropoietin on local-regional control in anemic patients treated with radiotherapy for squamous cell carcinoma of the head and neck.40

While darbepoetin alfa (novel erythropoiesis stimulating protein, NESP) has been approved by the Food and Drug Administration (FDA) for treating anemia in patients with chronic kidney disease (CKD), findings of clinical trials have demonstrated positive results in cancer patients as well. As has been shown in patients with CKD, Heatherington and colleagues found that the half-life of darbepoetin alfa is three times greater than that of epoetin in cancer patients, suggesting that this erythropoietic agent can be administered less frequently.41

In 89 anemic patients with nonmyeloid malignancies who were not receiving chemotherapy, Smith and colleagues found that darbepoetin alfa was well

tolerated. Increasing doses corresponded with increased efficacy, and most patients responded to treatment.42 In a more recent dosing study, Smith and colleagues evaluated 96 patients with nonmyeloid malignancies and chronic anemia, who were not receiving chemotherapy or radiation therapy. Darbepoetin alfa again was found to be safe and effective, with increased doses resulting in shorter time to response. In patients who received 6.75 mcg/kg every 3 (Q3W) or 4 (Q4W) weeks, serum concentrations of darbepoetin alfa were maintained above baseline for up to 3 to 4 weeks post-dose, and the terminal half-life was about 60 hours.43

Glaspy and colleagues assessed the efficacy of darbepoetin alfa in 107 cancer patients with solid tumors who were receiving multicycle chemotherapy. In three dose cohorts, the medication was found to be well tolerated, safe, and effective in increasing Hb levels.6 In a

12-week study involving 122 anemic patients with solid tumors who were receiving multicycle chemotherapy, the same researchers recently compared the efficacy of darbepoetin alfa to epoetin alfa. Patients were randomized to receive darbepoetin alfa in a 4-week front load phase followed by an 8-week maintenance phase that involved less frequent dosing or epoetin alfa at 40,000 units per week as a starting dose. After 12 weeks, 61% of patients treated with darbepoetin alfa responded to treatment compared to 49% of the patients treated with epoetin alfa, even when doses were increased to 60,000 units per week for those patients whose initial responses were inadequate. darbepoetin doses were not increased for patients who did not respond.44

Kotasek and colleagues recently evaluated the efficacy of darbepoetin alfa administered Q3W or Q4W, the same time frequency of most chemotherapy regimens. Data on 414 anemic patients with solid tumors on chemotherapy, who participated in the placebo-controlled trial, indicate that darbepoetin alfa can be safely and effectively administered very infrequently, allowing once per cycle dosing in patients receiving chemotherapy.45

Darbepoetin alfa is currently undergoing FDA review for use in the treatment of anemia in cancer patients receiving chemotherapy.

Recently, darbepoetin alfa (novel erythropoiesis stimulating protein, NESP), a longer-acting erythropoietic agent than epoetin, has been approved by the Food and Drug Administration for the treatment of patients with the anemia of CKD whether on dialysis or not. Due to longer serum half-life (25 hours vs. 8.5 hours), darbepoetin alfa should be administered less frequently than epoetin alfa. For example, patients who had been receiving epoetin once weekly should be administered darbepoetin alfa once every 2 weeks.55

Two large multicenter studies in dialysis patients who switched therapies demonstrated that darbepoetin alfa is as effective as epoetin in maintaining Hb levels.Similar comparability was demonstrated in a European multicenter study of CKD patients before the need for dialysis. In addition to less frequent dosing requirements, darbepoetin alfa appears to be well tolerated, with a safety profile comparable to that of epoetin.