Treatment of Neuroblastoma with a Novel Delayed Intensification Chemotherapy
To test the feasibility of adding a novel delayed intensification chemotherapy to a dose-intensive induction regimen chemotherapy for high-risk neuroblastoma.
Patients enrolled in this study received chemotherapy in accordance with the design of the NB97 trial. At the end of the therapy, patients received three cycles of delayed intensification chemotherapy. The delayed intensification chemotherapy consists of two A1 and one A2 cycle. The A1 cycle consists of 1.5 mg/m2 of vincristine on day 1, 1.2 g/m2 of cyclophosphamide on day 2, 100 mg/m2 of cisplatin on day 3, and 160 mg/m2 of etoposide on day 4. The A2 cycle is similar to the A1 cycle, however the only difference is that on day 4, 30 mg/m2 of doxorubicin is substituted for etoposide.
Between 2007 to 2011, a total of thirty-six patients were enrolled, sixteen patients were long term event-free survivors. Three patients were alive with tumor whilst fifteen patients died. The 3-year Event free survival (EFS) and Overall survival (OS) were 44.4% (95%CI, 27.4 to 61.5%) and 50% (95%CI, 32.8 to 67.2%) respectively.
A high rate of survival among patients with high-risk neuroblastoma was achieved with delayed intensification chemotherapy without the occurrence of a second malignancy.
KeywordsPediatric Neuroblastoma Chemotherapy Oncology Novel delayed intensification chemotherapy
Y-TZ: Conceptualized and designed the study, drafted the initial manuscript, and approved the final manuscript as submitted; JC, H-mX and Z-lL: Carried out the initial analyses, reviewed and revised the manuscript, and approved the final manuscript as submitted; Y-nL and X-dZ: Designed the data collection instruments, and coordinated and supervised data collection at two of the four sites, critically reviewed the manuscript, and approved the final manuscript as submitted. Z-lL will act as guarantor for this paper.
Compliance with Ethical Standards
Approved by Medical Ethics Committee of the First Hospital of Jilin University, Changchun, China. No: 2008–002.
Conflict of Interest
- 1.Park JR, Scott JR, Stewart CF, et al. Pilot induction regimen incorporating pharmacokinetically guided topotecan for treatment of newly diagnosed high-risk neuroblastoma: a children’s oncology group study. J Clin Oncol. 2011;29:4351–7.Google Scholar
- 3.Calafiore L, Amoroso L, Della Casa Alberighi O, et al. Two-stage phase II study of imatinib mesylate in subjects with refractory or relapsing neuroblastoma. Ann Oncol. 2013;24:1406–13.Google Scholar
- 5.Berthold F, Boos J, Burdach S, et al. Myeloablative megatherapy with autologous stem-cell rescue versus oral maintenance chemotherapy as consolidation treatment in patients with high-risk neuroblastoma: a randomised controlled trial. Lancet Oncol. 2005;6:649–58.Google Scholar
- 6.Cohn SL, Pearson AD, London WB, et al; INRG Task Force. The International Neuroblastoma Risk Group (INRG) classification system: an INRG task force report. J Clin Oncol. 2009;27:289–97.Google Scholar
- 7.Matthay KK, Villablanca JG, Seeger RC, et al. Treatment of high-risk neuroblastoma with intensive chemotherapy, radiotherapy, autologous bone marrow transplantation, and 13-cis-retinoic acid. N Engl J Med. 1999;341:1165–73.Google Scholar
- 9.Ambros IM, Benard J, Boavida M, et al. Quality assessment of genetic markers used for therapy stratification. J Clin Oncol. 2003;21:2077–84.Google Scholar
- 10.Berthold F, Hero B, Kremens B, et al. Long-term results and risk profiles of patients in five consecutive trials (1979-1997) with stage 4 neuroblastoma over 1 year of age. Cancer Lett. 2003;197:11–7.Google Scholar
- 11.Schmidt M, Simon T, Hero B, Schicha H, Berthold F. The prognostic impact of functional imaging with (123)I-mIBG in patients with stage 4 neuroblastoma >1 year of age on a high-risk treatment protocol: results of the German Neuroblastoma Trial NB97. Eur J Cancer. 2008;44:1552–8.CrossRefPubMedGoogle Scholar
- 14.Trotti A, Colevas AD, Setser A, et al. CTCAE v3.0: development of a comprehensive grading system for the adverse effects of cancer treatment. Semin Radiat Oncol. 2003;13:176–81.Google Scholar
- 16.Ladenstein R, Weixler S, Baykan B, et al. Ch14.18 antibody produced in CHO cells in relapsed or refractory stage 4 neuroblastoma patients: a SIOPEN phase 1 study. MAbs. 2013;5:801–9.Google Scholar