medwireNews: Busulfan and melphalan significantly improve event-free survival (EFS) over carboplatin, etoposide, and melphalan in children with high-risk neuroblastoma, with fewer severe adverse events, phase III clinical trial data show.
“Busulfan and melphalan should thus be considered standard high-dose chemotherapy” in these patients, Ruth Ladenstein (Medical University, Vienna, Austria) and colleagues remark.
For the study, 598 patients (aged 1–20 years) with high-risk neuroblastoma were randomly assigned to receive high-dose chemotherapy with busulfan and melphalan (n=296) or carboplatin, etoposide, and melphalan (n=302). The patients were followed-up for a median of 7.2 years.
To be eligible for randomization, the participants, who were recruited from 128 institutions in 18 countries, had to show a complete bone marrow response and at least a partial response at skeletal sites to a multidrug induction regimen with cisplatin, carboplatin, cyclophosphamide, vincristine, and etoposide with or without topotecan, vincristine, and doxorubicin.
At 3 years, 146 patients in the busulfan and melphalan group and 188 in the carboplatin, etoposide, and melphalan group experienced a first occurrence of relapse, progressive disease, secondary malignancy, or death from any cause, giving significantly different 3-year EFS rates of 50% versus 38%.
Five-year EFS and overall survival rates were also significantly higher with busulfan and melphalan than with carboplatin, etoposide, and melphalan, at 45% versus 33%, and 54% versus 41%, respectively.
In addition to improved survival rates, patients in the busulfan and melphalan group had fewer severe life-threatening toxicities (4% vs 10%) and fewer grade 3–4 adverse events, such as poor general condition (26 vs 38%), infection (19 vs 27%), and stomatitis (49 vs 59%).
Veno-occlusive disease, however, was more common with busulfan and melphalan than with carboplatin, etoposide, and melphalan (22 vs 9%).
The researchers also report a significant interaction between age and high-dose chemotherapy in which busulfan and melphalan only achieved better outcomes in patients aged 5 years or younger.
And on multivariate analysis, age older than 5 years was significantly associated with an increased risk for events during follow-up, irrespective of which treatment was received.
Therefore “patients older than 5 years need more effective treatments,” say Ladenstein et al.
Carboplatin, etoposide, and melphalan treatment, stage IV disease, and the absence of a complete response before high-dose chemotherapy were also associated with an increased risk for events during follow-up.
Ladenstein and co-authors caution in The Lancet Oncology that their findings “can only be applied to those patients who fulfil the strict randomisation criteria, and might be dependent on the type of induction therapy.”
They conclude: “[O]ngoing randomised studies will continue to aim to optimise treatment for high-risk neuroblastoma.”
By Laura Cowen
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