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In Reply

Virginia Commonwealth University, Richmond, VA

Ferretti and Papaldo make several good points in their letter. However, we would stop short of saying filgrastim (granulocyte colony-stimulating factor [G-CSF]) can be made cost effective in early breast cancer patients at low risk of febrile neutropenia (FN).

The trial on which they base their conclusions¹ has several important design characteristics that influenced our thinking. First, the FN rate (defined as a temperature of more than 38.2 °C concurrent with an absolute neutrophil count less than 0.5 x 10³/µL) was only 7%. Hence, none of those patients would be considered suitable candidates for primary prophylaxis under the American Society of Clinical Oncology, National Comprehensive Cancer Network, or European Society for Medical Oncology guidelines for prevention of FN. Second, the G-CSF schedule variation was not originally planned in the study design. No power calculations are available and the very small subgroups would have only minimal statistical certainty in appropriately assigning differences to the schedules of G-CSF. Although the FN rate in the G-CSF arm was 1% versus 7% in the control arm (P = .004), it is hard to interpret this given the post-hoc design and post-hoc statistical considerations; it is certainly not conclusive. We would be even more hesitant in saying that any of the separate arms using lower intensity G-CSF were different from each other. The accompanying editorial² in the Journal of Clinical Oncology stated, "the findings from the study by Papaldo et al are unlikely to be sufficient to inform changes in clinical practice, because of concerns related to both costs and quality of life."

The cost effectiveness ratios that they calculate would be highly subject to variations in the statistical certainty about the use of G-CSF. Hence, we would not be at all certain of the argument that adding two injections per cycles for four cycles would make any difference at all. Yes, it is the least expensive option, but it is probably unnecessary.

Experts in the field have counseled against developing individual metrics such as FN day for assessing cost effectiveness.^3,4 There has been much improper use of cost effectiveness⁵ since health economics was incorporated into decision making. Development of individual scales for each technology would lead to competition between $/FN day avoided versus $/vomiting day avoided. We need to be cognizant of the impact of these drugs on quality of life as well, and so far there is no evidence that CSFs cause major improvements. In addition, there is no reason that the cost of G-CSF or any other drug cannot be varied in these analyses. These drugs would be much more cost effective if they simply cost less, and there would be far less controversy over their use.

We applaud the better clinical outcomes seen with more aggressive chemotherapy regimens in the adjuvant treatment of breast cancer (see excellent review in the editorial by Hupperets and Tjan-Heijnen⁶) but we must recognize that these are expensive technologies that often cost hundreds of dollars a day. Unless they make a major impact on survival, quality adjusted survival, or avoid very expensive hospitalizations, they are unlikely to be cost saving. We should welcome the use of effective and cost effective medical interventions (which really means that their cost effectiveness ratio is less than $50 to $100,000 per additional life year), but we all must recognize that each one of these new therapies is additional money that society must spend. At some point, unless we want all our money spent on health care, we must strike a balance between trastuzamab, filgrastim, or a new targeted agent for each cancer patient.

Authors' Disclosures of Potential Conflicts of Interest

The authors indicated no potential conflicts of interest.

REFERENCES

1. Papaldo P, Lopez M, Marolla P, et al: Impact of five prophylactic filgrastim schedules on hematologic toxicity in early breast cancer patients treated with epirubicin and cyclophosphamide. J Clin Oncol 23:6908-6918, 2005[Abstract/Free Full Text]

2. Djulbegovic B, Frohlich A, Bennett CL: Acting on imperfect evidence: How much regret are we ready to accept? J Clin Oncol 23:6822-6825, 2005[Free Full Text]

3. Siegel JE, Weinstein MC, Russell LB, et al: Recommendations for reporting cost-effectiveness analyses. JAMA 276:1339-1341, 1996[Abstract/Free Full Text]

4. Weinstein MC, Siegel JE, Gold MR, et al: Recommendations of the panel on cost-effectiveness in health and medicine. JAMA 276:1253-1258, 1996

5. Udvarhelyi IS, Colditz GA, Rai A, et al: Cost-effectiveness and cost-benefit analyses in the medical literature: Are they being used correctly? Ann Intern Med 116:238-244, 1992[Abstract/Free Full Text]

6. Hupperets PS, Tjan-Heijnen VC: Primary or secondary G-CSF prophylaxis to support TAC chemotherapy in breast cancer? Ann Oncol 17:1181-1183, 2006[Free Full Text]

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This Article Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Alert me to new issues of the journal Save to my personal folders Download to citation manager Rights & Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Smith, T. J. Articles by Hillner, B. Search for Related Content PubMed Articles by Smith, T. J. Articles by Hillner, B. Social Bookmarking                            What's this?