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Keywords:

  • epoetin;
  • anaemia;
  • cancer

The recent articles on the use of once weekly epoetin beta (Cazzola et al, 2003) and darbepoetin alfa (Hedenus et al, 2003) highlight some important issues for the use of epoetin to treat anaemia in patients with cancer.

Both studies reported high response rates to a once weekly epoetin regimen in anaemic patients with lymphoproliferative malignancies [response defined as a 2 g/dl haemoglobin (Hb) increase]. In the epoetin beta trial, median time to response with epoetin beta once weekly was reported as 10·1 weeks (Cazzola et al, 2003). Further analysis using a more pragmatic approach to define time to response (two consecutive measurements rather than mean value over 4 weeks) suggests median response time may be closer to 8 weeks. Moreover, a clinically significant Hb increase of ≥1 g/dl was achieved within 4 weeks.

The need for a rapid Hb response is an important consideration in anaemic patients with cancer, especially those receiving chemotherapy during which anaemia and symptoms, such as fatigue, may worsen if untreated. For these patients, it is important that increases in Hb are achieved as early as possible during chemotherapy to ensure that their quality of life is improved. Comparison of response between the studies is not possible since these data were not reported by Hedenus et al (2003). However, a previous dose-ranging study in a similar patient cohort reported a median time to response of 12·1 weeks with a weekly dose of darbepoetin alfa 2·25 μg/kg (Hedenus et al, 2002)

Another important consideration is the potential need for dose adjustment with epoetin. The current usual practice is to increase the dose in patients with an inadequate Hb response. Both of these studies permitted dose increases after 4 weeks, although definitions of inadequate response differed. In the epoetin beta study, the dose was doubled to 60 000 IU weekly in patients whose Hb increased <0·5 g/dl from baseline (or who received transfusion) while in the darbepoetin alfa study, the dose was doubled to 4·5 μg/kg/week in patients with an increased Hb of <1·0 g/dl. In the epoetin beta study, 26% of patients in the once weekly arm and 23% in the three times weekly arm required doubling of dose (unpublished observations). The number of patients that required a dose increase with darbepoetin alfa was not reported. However, in a previous study of darbepoetin alfa, 43% of patients with lung cancer receiving chemotherapy required dose doubling because of inadequate response to 2·25 μg/kg once weekly (Vansteenkiste et al, 2002). This information is important in clinical practice, as increasing the dose during treatment will have a significant impact on treatment costs.

Time to treatment response and the need for dose modification are both significant issues that may influence epoetin treatment choice in clinical practice. Because of this, it is important that studies report these data.

Declaration of interest

  1. Top of page
  2. Declaration of interest
  3. References

The author has received research grants from F. Hoffmann-La Roche [manufacturer of NeoRecormon (epoetin beta)] and Amgen [manufacturer of Aranesp (darbepoietin alpha)], and has also acted as a Scientific Advisor for F. Hoffmann-La Roche and Ortho Biotech [manufacturer of Eprex (epoetin alpha)].

References

  1. Top of page
  2. Declaration of interest
  3. References
  • Cazzola, M., Beguin, Y., Kloczko, J., Spicka, I. & Coiffier, B. (2003) Once-weekly epoetin beta is highly effective in treating anaemic patients with lymphoproliferative malignancy and defective endogenous erythropoietin production. British Journal of Haematology, 122, 386393.
  • Hedenus, M., Hansen, S., Taylor, K., Arthur, C., Emmerich, B., Dewey, C., Watson, D., Rossi, G., Osterborg, A. & Darbepoetin Alfa 990114 Study Group (2002) Randomized, dose-finding study of darbepoetin alfa in anaemic patients with lymphoproliferative malignancies. British Journal of Haematology, 119, 7986.
  • Hedenus, M., Adriansson, M., San Migue, I.J., Kramer, M.H., Schipperus, M.R., Juvonen, E., Taylor, K., Belch, A., Altes, A., Martinelli, G., Watson, D., Matcham, J., Rossi, G., Littlewood, T.J. & Darbepoetin Alfa 20000161 Study Group (2003) Efficacy and safety of darbepoetin alfa in anaemic patients with lymphoproliferative malignancies: a randomized, double-blind, placebo-controlled study. British Journal of Haematology, 122, 394403.
  • Vansteenkiste, J., Pirker, R., Massuti, B., Barata, F., Font, A., Fiegl, M., Siena, S., Gately, J., Tomita, D., Colowick, A.B. & Musil, J. (2002) Double-blind, placebo-controlled, randomized phase III trial of darbepoetin alfa in lung cancer patients receiving chemotherapy. Journal of the National Cancer Institute, 94, 12111220.