Results of a phase II trial for high-risk neuroblastoma treatment protocol JN-H-07

a report from the Japan Childhood Cancer Group Neuroblastoma Committee (JNBSG)

For the Japan Childhood Cancer Group Neuroblastoma Committee (JNBSG)

Research output: Contribution to journalArticle

Abstract

Background: The Japanese Children’s Cancer Group (JCCG) Neuroblastoma Committee (JNBSG) conducted a phase II clinical trial for high-risk neuroblastoma treatment. We report the result of the protocol treatment and associated genomic aberration studies. Methods: JN-H-07 was a single-arm, late phase II trial for high-risk neuroblastoma treatment with open enrollment from June 2007 to February 2009. Eligible patients underwent five courses of induction chemotherapy followed by high-dose chemotherapy with hematopoietic stem cell rescue. Surgery for the primary tumor was scheduled after three or four courses of induction chemotherapy. Radiotherapy was administered to the primary tumor site and to any bone metastases present at the end of induction chemotherapy. Results: The estimated 3-year progression-free and overall survival rates of the 50 patients enrolled were 36.5 ± 7.0 and 69.5 ± 6.6%, respectively. High-dose chemotherapy caused severe toxicity including three treatment-related deaths. In response to this, the high-dose chemotherapy regimen was modified during the trial by infusing melphalan before administering carboplatin and etoposide. The modified high-dose chemotherapy regimen was less toxic. Univariate analysis revealed that patients younger than 547 days and patients whose tumor showed a whole chromosomal gains / losses pattern had a significantly poor prognosis. Notably, the progression-free survival of cases with MYCN amplification were not inferior to those without MYCN amplification. Conclusions: The outcome of patients treated with the JN-H-07 protocol showed improvement over the results reported by previous studies conducted in Japan. Molecular and genetic profiling may enable a more precise stratification of the high-risk cohort.

Original languageEnglish
Pages (from-to)1-9
Number of pages9
JournalInternational Journal of Clinical Oncology
DOIs
Publication statusAccepted/In press - 2018 Apr 26

Fingerprint

Clinical Protocols
Neuroblastoma
Japan
Induction Chemotherapy
Drug Therapy
Neoplasms
Disease-Free Survival
Phase II Clinical Trials
Melphalan
Poisons
Carboplatin
Etoposide
Hematopoietic Stem Cells
Molecular Biology
Radiotherapy
Therapeutics
Survival Rate
Neoplasm Metastasis
Bone and Bones

Keywords

  • Clinical trial
  • Genomic signature
  • High-risk
  • Multidisciplinary treatment
  • Neuroblastoma
  • Surgery

ASJC Scopus subject areas

  • Surgery
  • Hematology
  • Oncology

Cite this

Results of a phase II trial for high-risk neuroblastoma treatment protocol JN-H-07 : a report from the Japan Childhood Cancer Group Neuroblastoma Committee (JNBSG). / For the Japan Childhood Cancer Group Neuroblastoma Committee (JNBSG).

In: International Journal of Clinical Oncology, 26.04.2018, p. 1-9.

Research output: Contribution to journalArticle

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title = "Results of a phase II trial for high-risk neuroblastoma treatment protocol JN-H-07: a report from the Japan Childhood Cancer Group Neuroblastoma Committee (JNBSG)",
abstract = "Background: The Japanese Children’s Cancer Group (JCCG) Neuroblastoma Committee (JNBSG) conducted a phase II clinical trial for high-risk neuroblastoma treatment. We report the result of the protocol treatment and associated genomic aberration studies. Methods: JN-H-07 was a single-arm, late phase II trial for high-risk neuroblastoma treatment with open enrollment from June 2007 to February 2009. Eligible patients underwent five courses of induction chemotherapy followed by high-dose chemotherapy with hematopoietic stem cell rescue. Surgery for the primary tumor was scheduled after three or four courses of induction chemotherapy. Radiotherapy was administered to the primary tumor site and to any bone metastases present at the end of induction chemotherapy. Results: The estimated 3-year progression-free and overall survival rates of the 50 patients enrolled were 36.5 ± 7.0 and 69.5 ± 6.6{\%}, respectively. High-dose chemotherapy caused severe toxicity including three treatment-related deaths. In response to this, the high-dose chemotherapy regimen was modified during the trial by infusing melphalan before administering carboplatin and etoposide. The modified high-dose chemotherapy regimen was less toxic. Univariate analysis revealed that patients younger than 547 days and patients whose tumor showed a whole chromosomal gains / losses pattern had a significantly poor prognosis. Notably, the progression-free survival of cases with MYCN amplification were not inferior to those without MYCN amplification. Conclusions: The outcome of patients treated with the JN-H-07 protocol showed improvement over the results reported by previous studies conducted in Japan. Molecular and genetic profiling may enable a more precise stratification of the high-risk cohort.",
keywords = "Clinical trial, Genomic signature, High-risk, Multidisciplinary treatment, Neuroblastoma, Surgery",
author = "{For the Japan Childhood Cancer Group Neuroblastoma Committee (JNBSG)} and Tomoro Hishiki and Kimikazu Matsumoto and Miki Ohira and Takehiko Kamijo and Hiroyuki Shichino and Tatsuo Kuroda and Akihiro Yoneda and Toshinori Soejima and Atsuko Nakazawa and Tetsuya Takimoto and Isao Yokota and Satoshi Teramukai and Hideto Takahashi and Takashi Fukushima and Takashi Kaneko and Junichi Hara and Michio Kaneko and Hitoshi Ikeda and Tatsuro Tajiri and Akira Nakagawara",
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T2 - a report from the Japan Childhood Cancer Group Neuroblastoma Committee (JNBSG)

AU - For the Japan Childhood Cancer Group Neuroblastoma Committee (JNBSG)

AU - Hishiki, Tomoro

AU - Matsumoto, Kimikazu

AU - Ohira, Miki

AU - Kamijo, Takehiko

AU - Shichino, Hiroyuki

AU - Kuroda, Tatsuo

AU - Yoneda, Akihiro

AU - Soejima, Toshinori

AU - Nakazawa, Atsuko

AU - Takimoto, Tetsuya

AU - Yokota, Isao

AU - Teramukai, Satoshi

AU - Takahashi, Hideto

AU - Fukushima, Takashi

AU - Kaneko, Takashi

AU - Hara, Junichi

AU - Kaneko, Michio

AU - Ikeda, Hitoshi

AU - Tajiri, Tatsuro

AU - Nakagawara, Akira

PY - 2018/4/26

Y1 - 2018/4/26

N2 - Background: The Japanese Children’s Cancer Group (JCCG) Neuroblastoma Committee (JNBSG) conducted a phase II clinical trial for high-risk neuroblastoma treatment. We report the result of the protocol treatment and associated genomic aberration studies. Methods: JN-H-07 was a single-arm, late phase II trial for high-risk neuroblastoma treatment with open enrollment from June 2007 to February 2009. Eligible patients underwent five courses of induction chemotherapy followed by high-dose chemotherapy with hematopoietic stem cell rescue. Surgery for the primary tumor was scheduled after three or four courses of induction chemotherapy. Radiotherapy was administered to the primary tumor site and to any bone metastases present at the end of induction chemotherapy. Results: The estimated 3-year progression-free and overall survival rates of the 50 patients enrolled were 36.5 ± 7.0 and 69.5 ± 6.6%, respectively. High-dose chemotherapy caused severe toxicity including three treatment-related deaths. In response to this, the high-dose chemotherapy regimen was modified during the trial by infusing melphalan before administering carboplatin and etoposide. The modified high-dose chemotherapy regimen was less toxic. Univariate analysis revealed that patients younger than 547 days and patients whose tumor showed a whole chromosomal gains / losses pattern had a significantly poor prognosis. Notably, the progression-free survival of cases with MYCN amplification were not inferior to those without MYCN amplification. Conclusions: The outcome of patients treated with the JN-H-07 protocol showed improvement over the results reported by previous studies conducted in Japan. Molecular and genetic profiling may enable a more precise stratification of the high-risk cohort.

AB - Background: The Japanese Children’s Cancer Group (JCCG) Neuroblastoma Committee (JNBSG) conducted a phase II clinical trial for high-risk neuroblastoma treatment. We report the result of the protocol treatment and associated genomic aberration studies. Methods: JN-H-07 was a single-arm, late phase II trial for high-risk neuroblastoma treatment with open enrollment from June 2007 to February 2009. Eligible patients underwent five courses of induction chemotherapy followed by high-dose chemotherapy with hematopoietic stem cell rescue. Surgery for the primary tumor was scheduled after three or four courses of induction chemotherapy. Radiotherapy was administered to the primary tumor site and to any bone metastases present at the end of induction chemotherapy. Results: The estimated 3-year progression-free and overall survival rates of the 50 patients enrolled were 36.5 ± 7.0 and 69.5 ± 6.6%, respectively. High-dose chemotherapy caused severe toxicity including three treatment-related deaths. In response to this, the high-dose chemotherapy regimen was modified during the trial by infusing melphalan before administering carboplatin and etoposide. The modified high-dose chemotherapy regimen was less toxic. Univariate analysis revealed that patients younger than 547 days and patients whose tumor showed a whole chromosomal gains / losses pattern had a significantly poor prognosis. Notably, the progression-free survival of cases with MYCN amplification were not inferior to those without MYCN amplification. Conclusions: The outcome of patients treated with the JN-H-07 protocol showed improvement over the results reported by previous studies conducted in Japan. Molecular and genetic profiling may enable a more precise stratification of the high-risk cohort.

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KW - Neuroblastoma

KW - Surgery

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