Cancer Health Center

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The anthracycline that has been most used in induction regimens for children with AML is daunorubicin,[3,5,6] though idarubicin and the anthracenedione mitoxantrone have also been used.[8] A randomized study in children with newly diagnosed AML comparing daunorubicin with idarubicin (each given with cytarabine and etoposide) observed a trend favoring idarubicin in terms of remission rate, but use of idarubicin did not produce significant improvements in either EFS or OS.[8] Similarly, studies comparing idarubicin and daunorubicin in adults with AML have not produced compelling evidence that idarubicin is more efficacious than daunorubicin.[6] Excessive toxicity from IDA-DCTER compared with historical data from DCTER was reported in a CCG pilot study.[7] Preliminary results of the randomized comparison of daunorubicin or mitoxantrone combined with cytarabine and etoposide showed comparable complete remission rates and OS rates for the two induction regimens.[2] In the absence of convincing data that another anthracycline or mitoxantrone produces superior outcome to daunorubicin when given at an equitoxic dose, daunorubicin remains the anthracycline most commonly used during induction therapy for children with AML in the United States.

The intensity of induction therapy influences the overall outcome of therapy. The CCG-2891 study demonstrated that intensively timed induction therapy (4-day treatment courses separated by only 6 days) produced better EFS than standard-timing induction therapy (4-day treatment courses separated by 2 weeks or longer).[3] The MRC has intensified induction therapy by prolonging the duration of cytarabine treatment to 10 days.[5] Another way of intensifying induction therapy is by the use of high-dose cytarabine. While studies in nonelderly adults suggest an advantage for intensifying induction therapy with high-dose cytarabine (2-3 g/m² /dose) compared with standard-dose cytarabine,[12,13] a benefit for the use of high-dose cytarabine compared with standard-dose cytarabine in children was not observed using a cytarabine dose of 1 g/m² given twice daily for 7 days with daunorubicin and thioguanine.[14]

Hematopoietic growth factors such as granulocyte-macrophage colony-stimulating factor (GM-CSF) or granulocyte colony-stimulating factor (G-CSF) during AML induction therapy have been evaluated in multiple placebo-controlled studies in adults with AML in attempts to reduce the toxicity associated with prolonged myelosuppression.[15,16] These studies have generally shown a reduction of several days in the duration of neutropenia with the use of either G-CSF or GM-CSF [15] but have not shown significant effects on treatment-related mortality or OS.[15] A randomized study in children with AML evaluating G-CSF administered following induction chemotherapy showed a reduction in duration of neutropenia, but no difference in infectious complications or mortality.[17] Thus, routine prophylactic use of hematopoietic growth factors is not recommended for children with AML.

Treatment options under clinical evaluation

The following is an example of a national and/or institutional clinical trial that is currently being conducted. Information about ongoing clinical trials is available from the NCI Web site.

• AML08: St. Jude Children's Research Hospital is conducting a randomized trial for children with newly diagnosed AML. This trial compares two induction regimens: cytarabine/daunorubicin/etoposide (ADE) versus clofarabine/cytarabine. Responses are assessed via morphology and flow cytometry (MRD) at the end of the induction phase.
• COG-AAML1031