Doxorubicin-Induced Myocardial Injury
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《新英格兰医药杂志》
To the Editor: Lipshultz et al. (July 8 issue)1 show that dexrazoxane reduces the cardiac toxicity of doxorubicin without compromising the antileukemic effects. Although dexrazoxane is a promising cardioprotective agent, physicians might suspect that it reduces both the adverse and the beneficial effects of doxorubicin. Since the rate of complete remission is affected by the characteristics of the patient, monitoring of event-free survival is not sufficient to show that dexrazoxane does not reduce the antileukemic effects of doxorubicin. To show that dexrazoxane specifically affects the myocardium, the rates of noncardiac adverse events, such as myelosuppression and mucositis, would be helpful.
George Fujisaki, M.D.
Chiho Inokuchi, M.D.
Naoko Murashige, M.D.
National Cancer Center Hospital
Tokyo 104-0045, Japan
nmurashi@ncc.go.jp
References
Lipshultz SE, Rifai N, Dalton VM, et al. The effect of dexrazoxane on myocardial injury in doxorubicin-treated children with acute lymphoblastic leukemia. N Engl J Med 2004;351:145-153.
The authors reply: Induction failure due to persistent leukemia was observed in 4 percent of patients randomly assigned to doxorubicin alone and 2.9 percent of patients randomly assigned to doxorubicin and dexrazoxane. The rate of complete remission for patients who were randomly assigned to receive doxorubicin alone was 95 percent, as compared with 96 percent for those randomly assigned to receive doxorubicin and dexrazoxane. These data, along with similar data on event-free survival that appeared in our article (83 percent in both groups; P=0.87 by the log-rank test), suggest that dexrazoxane did not interfere with the antileukemic efficacy of doxorubicin.
In terms of toxicity, the patients in both treatment groups had similar and low rates of lethal toxic effects: during induction, deaths occurred in 1 percent of the patients receiving doxorubicin alone and in 1 percent of the patients receiving both drugs, and deaths during remission in 2 percent of patients receiving doxorubicin alone and in 1 percent of the patients receiving both drugs. Mucositis and myelosuppression were not measured prospectively; clinically, however, the incidence and magnitude of both events were consonant with our experience over decades with essentially the same basic chemotherapy "backbone" to which we added dexrazoxane for this trial.
Steven E. Lipshultz, M.D.
University of Miami School of Medicine
Miami, FL 33101
slipshultz@med.miami.edu
Lewis B. Silverman, M.D.
Stephen E. Sallan, M.D.
Dana–Farber Cancer Institute
Boston, MA 02115
George Fujisaki, M.D.
Chiho Inokuchi, M.D.
Naoko Murashige, M.D.
National Cancer Center Hospital
Tokyo 104-0045, Japan
nmurashi@ncc.go.jp
References
Lipshultz SE, Rifai N, Dalton VM, et al. The effect of dexrazoxane on myocardial injury in doxorubicin-treated children with acute lymphoblastic leukemia. N Engl J Med 2004;351:145-153.
The authors reply: Induction failure due to persistent leukemia was observed in 4 percent of patients randomly assigned to doxorubicin alone and 2.9 percent of patients randomly assigned to doxorubicin and dexrazoxane. The rate of complete remission for patients who were randomly assigned to receive doxorubicin alone was 95 percent, as compared with 96 percent for those randomly assigned to receive doxorubicin and dexrazoxane. These data, along with similar data on event-free survival that appeared in our article (83 percent in both groups; P=0.87 by the log-rank test), suggest that dexrazoxane did not interfere with the antileukemic efficacy of doxorubicin.
In terms of toxicity, the patients in both treatment groups had similar and low rates of lethal toxic effects: during induction, deaths occurred in 1 percent of the patients receiving doxorubicin alone and in 1 percent of the patients receiving both drugs, and deaths during remission in 2 percent of patients receiving doxorubicin alone and in 1 percent of the patients receiving both drugs. Mucositis and myelosuppression were not measured prospectively; clinically, however, the incidence and magnitude of both events were consonant with our experience over decades with essentially the same basic chemotherapy "backbone" to which we added dexrazoxane for this trial.
Steven E. Lipshultz, M.D.
University of Miami School of Medicine
Miami, FL 33101
slipshultz@med.miami.edu
Lewis B. Silverman, M.D.
Stephen E. Sallan, M.D.
Dana–Farber Cancer Institute
Boston, MA 02115