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Can the Addition of Prophylactic Filgrastim Be Considered Cost Effective in Early Breast Cancer Patients Treated With Epirubicin and Cyclophosphamide?

Division of Medical Oncology A, Regina Elena Cancer Institute, Rome, Italy

To the Editor:

In their article "2006 Update of Recommendations for the Use of White Blood Cell Growth Factors," Smith et al,¹ commenting on our study,² assert that "the more important parameter, febrile neutropenia, was observed in only 7% of non-granulocyte colony stimulating factor patients, so colony stimulating factors would not have been suggested under existing guidelines." ¹

Actually, the febrile neutropenia (FN) rate in our granulocyte colony stimulating factor (G-CSF) arm was 1% v 7% in the control arm (P = .004). In particular, the short schedule (300 µg of G-CSF subcutaneously on days 8 and 12, schedule 5) was equivalent to the daily schedules (480 or 300 µg/d of G-CSF on days 8 through 14) and to the every-other-day schedules (480 or 300 µg/d of G-CSF on days 8, 10, 12, and 14) with respect to incidence of neutropenic fever (2% v 0%; P = .74; and 2% v 2%; P = .56, respectively).

Considering that the cost of each prefilled syringe containing 300 µg of G-CSF is approximately 150 euro, the incremental cost of adding two G-CSF injections according to schedule 5 would be 1,200 euros per patient (eight injections total; two injections per cycle for four cycles). This implies an incremental cost-effectiveness ratio of 240 euros (1,200 euros/5% risk reduction with schedule 5) per percent decrease of the probability of FN.

According to Timmer-Bonte et al,³ only if one is willing to pay 240 euros for each percent gain in effect, can the addition of G-CSF to primary prophylaxis with antibiotics be considered cost effective. In the same study,³ comparing the antibiotics arm versus the antibiotics plus G-CSF arm, no difference was observed in the combined cost of chemotheraputic agents (cyclophosphamide 1,000 mg/m² day 1, doxorubicin 45 mg/m² day 1, etoposide 100 mg/m² days 1 through 3, every 21 days for five cycles; cyclophosphamide, doxorubicin, etoposide [CDE]), antibiotics (ciprofloxacin plus roxithromycin), or non-FN hospitalizations.

Thus, we think that the addition of two injections of G-CSF to epirubicin and cyclophosphamide (EC; epirubicin 120 mg/m² and cyclophosphamide 600 mg/m² IV on day 1 every 21 days for four cycles) can be considered cost effective (240 euros for each percent decrease of the probability of FN). It is worth noting that our early breast cancer women did not receive prophylaxis with antibiotics. Prophylactic ciprofloxacin plus roxithromycin remarkably reduced the incidence of FN and proved cost effective in small-cell lung cancer patients receiving CDE.³ Though among patients receiving chemotherapy for solid tumors or lymphoma the prophylactic use of levofloxacin has been reported to reduce the incidence of fever, probable infection, and hospitalization,⁴ there is concern regarding the emergence of resistant microorganisms when prophylactic antibiotics are given.⁵ However, this risk does not appear to be statistically significant,⁶ and the benefit (decrease in the risk of infection-related death) seems to outweigh harm (development of resistance)⁷ so far.

It must be highlighted that we did not subtract from the amount of 1,200 euros the eventual cost savings deriving from the reduced incidence of FN by using two injections of G-CSF.

Authors' Disclosures of Potential Conflicts of Interest

The authors indicated no potential conflicts of interest.

REFERENCES

1. Smith TJ, Khatcheressian J, Lyman GH, et al: 2006 update of recommendations for the use of white blood cell growth factors: An evidence-based clinical practice guideline. J Clin Oncol 24:3187-3205, 2006[Abstract/Free Full Text]

2. 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]

3. Timmer-Bonte JN, Adang EM, Smit HJ, et al: Cost-effectiveness of adding granulocyte colony-stimulating factor to primary prophylaxis with antibiotics in patients with small-cell lung cancer. J Clin Oncol 24:2991-2997, 2006[Abstract/Free Full Text]

4. Cullen M, Steven N, Billingham L, et al: Antibacterial prophylaxis after chemotherapy for solid tumors and lymphomas. N Engl J Med 353:988-998, 2005[Abstract/Free Full Text]

5. Hughes WT, Armstrong D, Bodey GP, et al: 2002 guidelines for the use of antimicrobial agents in neutropenic patients with cancer. Clin Infect Dis 34:730-751, 2002[CrossRef][Medline]

6. Gafter-Gvili A, Fraser A, Paul M, et al: Meta-analysis: Antibiotic prophylaxis reduces mortality in neutropenic patients. Ann Intern Med 142:979-995, 2005[Abstract/Free Full Text]

7. Gafter-Gvili A, Fraser A, Paul M, et al: Antibiotic prophylaxis for bacterial infections in afebrile neutropenic patients following chemotherapy. Cochrane Database Syst Rev 2005:CD004386

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