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Combination chemotherapy consisting of irinotecan, etoposide, and carboplatin (IREC) for refractory or relapsed neuroblastoma
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  • Masayuki Imaya,
  • Hideki Muramatsu,
  • Atsushi Narita,
  • Ayako Yamamori,
  • Manabu Wakamatsu,
  • Taro Yoshida,
  • Shunsuke Miwata,
  • Kotaro Narita,
  • Daisuke Ichikawa,
  • Motoharu Hamada,
  • Eri Nishikawa,
  • Nozomu Kawashima,
  • Nobuhiro Nishio,
  • Seiji Kojima,
  • Yoshiyuki Takahashi
Masayuki Imaya
Nagoya University Graduate School of Medicine
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Hideki Muramatsu
Nagoya University Graduate School of Medicine
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Atsushi Narita
Nagoya University Graduate School of Medicine
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Ayako Yamamori
Nagoya University Graduate School of Medicine
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Manabu Wakamatsu
Nagoya University Graduate School of Medicine
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Taro Yoshida
Nagoya University Graduate School of Medicine
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Shunsuke Miwata
Nagoya University Graduate School of Medicine
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Kotaro Narita
Nagoya University Graduate School of Medicine
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Daisuke Ichikawa
Nagoya University Graduate School of Medicine
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Motoharu Hamada
Nagoya University Graduate School of Medicine
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Eri Nishikawa
Nagoya University Graduate School of Medicine
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Nozomu Kawashima
Nagoya University Graduate School of Medicine
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Nobuhiro Nishio
Nagoya University Hospital
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Seiji Kojima
Nagoya University Graduate School of Medicine
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Yoshiyuki Takahashi
Nagoya University Graduate School of Medicine
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Abstract

Background: Patients with relapsed or refractory neuroblastoma have a poor prognosis; there are limited effective and safe rescue chemotherapies for these patients. Development of new chemotherapy regimens for these patients is a key imperative. Procedure: We retrospectively analyzed patients with refractory or relapsed neuroblastoma who received irinotecan, etoposide, and carboplatin (IREC) as a second-line treatment for neuroblastoma. We evaluated the therapeutic response, toxicity, and survival outcomes. We also assessed the impact of UGT1A1 gene polymorphisms, which are involved in irinotecan metabolism, on the outcomes and toxicity. Results: A total of 131 cycles of IREC were administered to 43 patients with a median of two cycles per patient (range, 1–10). All patients were classified as high-risk (International Neuroblastoma Risk Group). Seven patients had relapsed before IREC. One patient (2%) showed partial response and 37 patients (86%) developed stable disease (disease control rate: 88%). Grade IV neutropenia was observed in 127 cycles (97%), while ≥ grade III gastrointestinal toxicity was observed in 3 cycles (2%). There was no IREC-related mortality. The one-year overall survival and progression-free survival rates were 65% and 52%, respectively. Patients with UGT1A1 polymorphisms showed a higher frequency of grade IV neutropenia; however, there was no increase in treatment-related mortality or nonhematological toxicity in these patients. Patients with UGT1A1 gene polymorphisms showed better one-year survival rate than the wild type (80% vs. 44%, p = 0.012). Conclusions: This study suggests that IREC is well-tolerated by patients with UGT1A1 polymorphisms and is a promising second-line chemotherapy for refractory/relapsed neuroblastoma.