Dexrazoxane Not Linked with Secondary Cancers in Children with ALL

By Scott Baltic

NEW YORK MAR 19, 2008 (Reuters Health) - Dexrazoxane, which is used to prevent anthracycline-induced myocardial toxicity, does not appear to increase the risk of secondary malignant neoplasms in children with high-risk acute lymphoblastic leukemia (ALL), according to a paper in the March 1 issue of the Journal of Clinical Oncology.

The study, conducted by Dr. Elly V. Barry at the Dana-Farber Cancer Institute in Boston and colleagues, involved an analysis of data from a randomized trial carried out between 1996 and 2000. The analysis was undertaken in response to a study, published in the same journal in February 2007, that reported an increased risk for acute myeloid leukemia/myelodysplastic syndrome and other secondary malignancies in children with Hodgkin"s disease who received dexrazoxane.

Of 205 pediatric patients in the present study, 100 were randomized to receive doxorubicin alone, and 105 were assigned to receive doxorubicin with dexrazoxane. High-risk patients were defined as those younger than 1 year of age or over 10 years of age, with a white blood cell count of at least 50,000/µL; and with the presence of T-cell immunophenotype, the Philadelphia chromosome, a radiologic mediastinal mass or evidence of CNS-2 or CNS-3 leukemia.

At a median follow-up of 6.2 years, high-risk and standard-risk patients did not differ significantly in terms of the rate of complete remission, number or types of relapses, event-free survival, overall survival or occurrence of death in remission or relapse.

Two secondary malignant neoplasms (both melanomas) occurred among the 205 subjects, one in an 11-year-old patient who was 2 years old when ALL was diagnosed, and the other in a 17-year-old patient who was 14 when ALL was diagnosed. Neither patient had received dexrazoxane.

In the 2007 report, a total of 10 secondary malignant neoplasms had been noted among 478 subjects, 8 of them in the dexrazoxane-treated group (P = 0.06).

"Our findings ... serve as a note of caution in the interpretation and generalization of the results" of the 2007 report, the authors of the present study write.

Seeking to explain the differences in the two studies, the present authors note that, among other possible factors, the cumulative incidences of secondary malignant neoplasms after childhood and adolescent Hodgkin"s disease are roughly 4 to 6 times as high as they are after childhood ALL.

The authors conclude by recommending continued use of dexrazoxane in pediatric ALL regimens containing doxorubicin and that it be considered for use in other cases in which pediatric cancer patients are receiving relatively high doses of anthracyclines, with ongoing monitoring for cardiotoxicity and secondary malignant neoplasms.

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