RESPONSE: Re: Double-Blind, Placebo-Controlled, Randomized Phase III Trial of Darbepoetin Alfa in Lung Cancer Patients Receiving Chemotherapy

Dr. VanAudenrode raises several issues regarding our study (1), including the appropriateness of identifying new research hypotheses in our discussion, of directly comparing costs of Aranesp (darbepoetin alfa) with Procrit (epoetin alfa) in the United States, and of potentially offsetting erythropoietic therapy costs with the possible reduction in duration of hospitalization compared with placebo. Our study presented a new approach for treating cancer-related anemia and aimed to be a good contribution to the literature on symptom management in cancer patients. We learned from Varricchio and Sloan (2), who state “… that researchers should present the complete data and put them in the proper context so that the readers have information on which to judge the merits of this study,” that we probably achieved our goal. Our study (1) was a placebo-controlled, randomized, phase III study; therefore, making a direct comparison between the dose requirements and therapeutic effect of darbepoetin alfa and epoetin alfa was impossible from this dataset. Accordingly, no comparison was made. However, because our study demonstrated the effects of weekly darbepoetin alfa administration, we felt it appropriate to comment on the potential benefits of a weekly administration schedule and to compare that with the American Society of Hematology/American Society for Clinical Oncology guideline (3) of the recommended and labeled dosing regimen of epoetin alfa (3 times per week) (see 2002 package insert for Procrit; Ortho Biotech, Raritan, NJ). Dr. VanAudenrode acknowledges the benefits of weekly therapy, citing a two-thirds reduction in visit and administration costs, but he misquotes us with regard to patient compliance, suggesting that we made a conclusive statement in this regard. In fact, we merely suggested that “. . . other benefits [of weekly therapy] . . . include potentially better patient compliance.” Patients treated with darbepoetin alfa at a dose of 1.5 μg/kg and 3.0 μg/kg every 2 weeks (approximately 100 and 200 μg for a patient weighing 70 kg, respectively) achieved a response similar to those in the contemporaneous epoetin alfa control arms (4,5). Consequently, in the United States, 1.5 μg/kg darbepoetin alfa every week is an effective starting dose (see 2002 package insert for Aranesp [darbepoetin alfa]; Amgen, Thousand Oaks, CA). Additionally, the darbepoetin alfa dose of 200 μg every 2 weeks has been adopted in the United States as the standard dosing regimen for cancer-related anemia. Based on results from a randomized study comparing every-2-week administration of darbepoetin alfa and weekly administration of epoetin alfa, Glaspy et al. (6) presented cost-effective analysis data using an average wholesale price-based assessment. For the 12-week trial duration, the acquisition cost of epoetin alfa was more than 11% more expensive, and the response rates were identical (60%, with similar confidence intervals) for the two therapies, with a smaller percentage of those in the darbepoetin alfa group (3% versus 7%) requiring red blood cell transfusions. Glaspy et al. (6) concluded that, compared with epoetin alfa administered weekly, 3.0 μg/kg darbepoetin alfa administered every 2 weeks (200 μg) was less expensive and therefore was a cost-effective alternative for treating anemia in cancer patients receiving chemotherapy. Because pharmaceutical product pricing differs in other regions of the world, with the costs of both agents varying according to territory (including Canada, Dr. VanAudenrode’s country of residence), his calculations are inapplicable to these countries. Consequently, cost assessments have to be tailored to the adopted dosing schedule and price of each agent within the relevant country. We agree with Dr. VanAudenrode that the claim regarding reduction in the duration of hospitalization is not fully substantiated. It was not our intent to indicate as such. Despite the study not being formally designed to evaluate cost reduction with respect to hospitalization, we reported an observation indicating a possible trend toward shorter hospital stays for patients given darbepoetin alfa than for those given placebo. We acknowledged in the “Discussion” section of our article the limitations of the study to address this issue conclusively but speculated that, if proven through prospective clinical research, it would be an important finding with the potential to offset the costs of these expensive therapies.

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