However, investigators cautioned that the drug was also associated with a greater risk of serious side effects, including invasive infections. Also, dexamethasone(Drug information on dexamethasone) may not be justified except in children who have relapsed and failed rescue treatments, said Martin Schrappe, MD, of the University Medical Center Schleswig-Holstein in Kiel, Germany. Dr. Schrappe was the lead investigator for the multicenter trial AIEOP-BFM ALL 2000.
"We have a responsibility not to use any regimen in ALL that will endanger the patient in the first few weeks of treatment, and the toxicity profile of dexamethasone is considerable," Dr. Schrappe said. "Although it's more effective, it's also more toxic."
If dexamethasone is used, it needs to be accompanied by intensive clinical monitoring and early antimicrobial therapy, he said.
The investigators randomized 3655 children with ALL (ages one to 17), to receive induction therapy of prednisone(Drug information on prednisone) (60 mg/m2/d) or dexamethasone (10 mg/m2/d) in addition to therapy with daunorubicine, vincristine, and L-asparaginase combination therapy. All children were pretreated with prednisone and intrathecal methotrexate(Drug information on methotrexate) (abstract 7).
The results showed that after six years, event-free survival was 84.1% in patients who received the dexamethasone combination compared with 79.1% who received prednisone in the induction phase. For patients randomized to dexamethasone, the six-year incidence of relapse was 11% versus 18% for those on prednisone.
The investigators noted that dexamethasone has been used successfully in later phases of treatment for ALL, so it made sense to assess its effects in the induction phase. However, the toxicity seen in this study was enough to convince the researchers that it should be used with caution in the early phases of treatment for patients with ALL.
In the trial, patients on dexamethasone had a higher incidence of severe immunosuppression and infections, including fungal infections. Although its effectiveness led to a significant benefit in terms of event-free survival, the toxicity was also disturbing. The cumulative incidence for death in the dexamethasone arm was 2% compared to 0.9% with prednisone, a significant difference.
"Using dexamethasone is a decision that needs to be evaluated based on the individual patient. Although it's very effective in reducing late relapses, it's also more toxic," Dr. Schrappe said.