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In Reply:

For the French Adjuvant Study Group, France

We thank Dr Ventura for his letter. However, his conclusions are debatable for several reasons. First, the aim of our study¹ was to compare the long-term cardiotoxicity of two different doses of epirubicin, not to compare the cardiotoxicity profiles of the anthracyclines doxorubicin and epirubicin. Furthermore, several studies have shown that epirubicin is equally effective as and less cardiotoxic than doxorubicin at equimolar doses (Jain et al, ² Torti et al,³ and Ewer et al⁴). However, there have been no studies to date that have evaluated the efficacy and toxicity of these anthracyclines at their optimal doses (ie, doxorubicin at 60 mg/m² v epirubicin at 100 to 120 mg/m²). As documented in earlier studies, there appears to be no dose response–effect relationship with doxorubicin beyond 50 to 60 mg/m² in clinical trials of breast cancer, whereas in our French Adjuvant Study Group 05 (FASG 05) clinical trial, a dose response relationship does exist with epirubicin beyond 50 to 60 mg/m² and demonstrates a significant improvement in 10- year disease-free survival and overall survival when epirubicin is used at a dose of 100 mg/m² in combination with fluorouracil and cyclophosphamide (FEC100) versus the lower FEC50 dose. It is not scientifically valid to compare the results of two different clinical studies, particularly because the tumor types were different and the chemotherapy regimens varied due to the wide dose range of anthracycline doses. In Hequet's study,⁵ one case of CHF in 141 patients has been observed in the overall population regardless of the anthracycline dose. In our study, two CHF cases possibly related to epirubicin have been observed in 150 node-positive breast cancer patients. Among our FASG 05 breast cancer patients, 96% had also received locoregional irradiation following chemotherapy to prevent local recurrence per protocol. The two patients who developed CHF had received left chest wall and nodal irradiation and, thus, irradiation may have been a contributing factor in development of late cardiac sequelae in these women. It should be noted that the percentages given in Dr Ventura's letter are not correct. To our knowledge, Habeshaw's study⁶ was a comparison between two different doses of epirubicin and not a comparison between doxorubicin and epirubicin. Finally, the FASG cannot speak about the cost of doxorubicin and epirubicin as it differs a lot between countries. Irrespective of cost, based on our extensive clinical experience over the past 15 years, we have observed meaningful clinical differences between these anthracyclines; thus, epirubicin remains our clinical standard.

Author's Disclosures of Potential Conflicts of Interest

The author indicated no potential conflicts of interest.

Acknowledgment

The authors whish to acknowledge Dr Gabriel N. Hortobagyi for reviewing this letter.

REFERENCES

1. Bonneterre J, Roche H, Kerbrat P, et al: Long term cardiac follow-up in relapse free patients after six courses of fluorouracil, epirubicin and cyclophosphamide, with either 50 or 100 mgof epirubicin as adjuvant therapy for node-positive breast cancer: French Adjuvant Study Group. J Clin Oncol 22:3070-3079, 2004[Abstract/Free Full Text]

2. Jain KK, Casper ES, Geller NL, et al: A prospective randomized comparison of epirubicin and soxorubicin in patients with advanced breast cancer . J Clin Oncol 3:818-826, 1985[Abstract/Free Full Text]

3. Torti FM, Bristow MM, Blum BL, et al: Cardiotoxicity of epirubicin and doxorubicin: Assessment by endomyocardial biopsy. Cancer Res 46:3722-3727, 1986[Abstract/Free Full Text]

4. Ewer MS, Benjamin RS: Cardiac complications, in Holland J, Frei E, et al (eds), Cancer Medicine (ed 5), 2000, Williams and Wilkins, Baltimore, MD, pp 2324-2339

5. Hequet O, Le QH, Moullet I, et al: Subclinical late cardiomyopathy after doxorubicin therapy for lymphoma in adults. J Clin Oncol 22:1864-1871, 2004[Abstract/Free Full Text]

6. Habeshaw T, Paul J, Jones R, et al: Epirubicin at two dose levels with prednisolone as treatment for advanced breast cancer: The results of a randomized trial. J Clin Oncol 9:295-304, 1991[Abstract]

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Related Correspondence

• Cardiotoxicity of Epirubicin Versus Doxorubicin: Cost and Clinical Results
  Gerard J. Ventura
  JCO 2005 23: 2873 [Full Text]

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 Bonneterre, J. Search for Related Content PubMed Articles by Bonneterre, J. Related Articles Related Correspondence Social Bookmarking                            What's this?