治療により小児神経芽腫の生存率が改善する（Abstract No.2）

新たな高用量化学療法レジメンにより難治性神経芽腫の小児の生存率が改善する
New high-dose chemotherapy regimen improves survival in children with hard-to-treat neuroblastoma
高リスク神経芽腫の小児における骨髄破壊的化学療法薬ブスルファンとメルファランの併用（BuMel）による無イベント生存率および生存率は、カルボプラチン、エトポシドおよびメルファラン（CEM）の3種類の化学療法薬による異なる骨髄破壊的療法と比較し良好であるとのスタディ結果が2011年ASCOで発表された。ヨーロッパSIOP神経芽腫グループが行ったHR-NLB1トライアルはこれら2種類の高用量骨髄破壊的化学療法レジメンの有効性を比較した。このトライアルではステージIVの遠隔転移またはMYCN腫瘍遺伝子増幅を有する高リスクの小児563人（年齢中央値3歳）を、BuMel（281人）またはCEM（282人）投与群に無作為に割り付けた。3年後の無イベント生存率はBuMel群で49%であったのに対しCEM群では33%であった。3年後の全生存率はBuMel投与群の60%に対し、免疫療法を行わないCEM群では48%であり、ブスルファン群の方が再発および進行率が低かった（47%対60%）。しかし、神経芽腫の治療にはリスクを伴わないわけではない。治療関連死はBuMel群で3%であり、CEM群で5%であった。これらの結果に基づき、無作為化は早期に中止された。
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A randomized Phase III trial showed that children with high-risk neuroblastoma had better event-free and overall survival with a combination of the myeloablative chemotherapy drugs busulphan and melphalan (BuMel) compared to a different myeloablative regimen of three chemotherapy drugs, carboplatin, etoposide and melphalan (CEM). These results establish a new standard of care for children with high-risk disease, of whom previously only 30 percent survive long-term. Myeloablative chemotherapy is high-dose chemotherapy that kills cells in the bone marrow, including cancer cells.

"The study's results are important for patients with this extremely difficult to treat disease," said lead author Ruth Ladenstein, M.D., MBA, associate professor of pediatrics at the University of Vienna and St. Anna Children's Cancer Research Institute in Vienna. "These results, combined with the recent report that an anti-GD2 ch14.18 antibody-based immune therapy can increase event-free and overall survival by 20 percent in high-risk patients, mean that we could potentially improve overall prognosis by up to 35 percent in the future. Thus, we overcome the 50 percent threshold in survival rates by choosing the right high-dose myeloablative regimen for these patients."

Neuroblastoma is a rare cancer of specialized nerve cells, but it is the most common cancer in the first year of life and accounts for approximately 15 percent of childhood cancer deaths. About 650 cases are diagnosed each year in the United States, with about 40 percent that are considered high-risk, meaning they are very likely to recur or progress, despite therapy. The typical therapy for these patients includes intense upfront chemotherapy to induce remission, surgery, radiotherapy, myeloablative therapy to kill the cancer cells remaining in the bone marrow combined with stem cell transplantation, and followed by minimal residual disease treatment with 13 cis retinoid acid, as well as immunotherapy if available.

The HR-NLB1 trial of the European SIOP Neuroblastoma Group compared the effectiveness of two high-dose myeloablative chemotherapy regimens. In the trial, 563 children (median age three) with stage IV, high-risk disease with distant metastases or local disease with MYCN oncogene amplification were randomized to receive either BuMel (281) or CEM (282). After three years, the event-free survival for BuMel was 49 percent compared to 33 percent for the CEM group. The overall survival after three years was 60 percent for those who received BuMel compared to 48 percent in the CEM group without immunotherapy, and the busulphan group had lower rates of relapse and progression (47 percent versus 60 percent). Based on the results, the randomization was stopped early.

Treatment for neuroblastoma is not without risk. The treatment-related death rate was 3 percent for the busulphan regimen and 5 percent for CEM.