Short topotecan-based induction regimen in newly diagnosed high-risk neuroblastoma

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Abstract

Purpose: Topotecan is an active drug in relapsed neuroblastoma. We investigated the efficacy and toxicity of a topotecan-based induction regimen in newly diagnosed neuroblastoma. Methods: Patients older than 1 year with either metastatic or localised stage 2-3 MYCN-amplified neuroblastoma received 2 courses of high-dose topotecan (HD-TPT) 6 mg/m2 and high-dose cyclophosphamide (HD-CPM) 140 mg/kg, followed by 2 courses of ifosfamide, carboplatin and etoposide (ICE) every 28 days. After surgery on primary tumour, a fifth course with vincristine, doxorubicin and CPM was given, followed by high-dose chemotherapy with stem cell support. Response was assessed in accordance with the International Neuroblastoma Response Criteria. Results: Of 35 consecutive patients, 33 had metastatic disease. The median length of induction phase was 133 days (range 91-207) and time to high-dose chemotherapy was 208 days (range 156-285). The median tumour volume reduction was 55% after two HD-TPT/HD-CPM courses and 80% after four courses. Radical surgery was performed in 16/27 patients after chemotherapy. After the fifth course, 29/34 patients (85%) had achieved a partial remission (12) or a CR/very good partial remission (17). CR of metastases was achieved in 13/32 (41%) and bone marrow was in complete remission in 16/24 patients (67%). Grade 4 neutropenia and/or thrombocytopenia occurred in 100% of HD-TPT/HD-CPM and in 95% of ICE courses, while non-haematological toxicities were manageable. Conclusions: These data indicate that our induction regimen is feasible and well tolerated. A major response rate of 85% with 41% complete metastatic response confirms this regimen as effective induction in high-risk neuroblastoma.

Original languageEnglish
Pages (from-to)572-578
Number of pages7
JournalEuropean Journal of Cancer
Volume47
Issue number4
DOIs
Publication statusPublished - Mar 2011

Fingerprint

Topotecan
Neuroblastoma
Cyclophosphamide
Ifosfamide
Carboplatin
Etoposide
Drug Therapy
Vincristine
Neutropenia
Tumor Burden
Thrombocytopenia
Doxorubicin
Stem Cells
Bone Marrow
Neoplasm Metastasis
Pharmaceutical Preparations
Neoplasms

Keywords

  • Children
  • Induction
  • Metastasis
  • Neuroblastoma
  • Remission
  • Topotecan

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

@article{bc0ea5a520714f799f60283744d2bfb5,
title = "Short topotecan-based induction regimen in newly diagnosed high-risk neuroblastoma",
abstract = "Purpose: Topotecan is an active drug in relapsed neuroblastoma. We investigated the efficacy and toxicity of a topotecan-based induction regimen in newly diagnosed neuroblastoma. Methods: Patients older than 1 year with either metastatic or localised stage 2-3 MYCN-amplified neuroblastoma received 2 courses of high-dose topotecan (HD-TPT) 6 mg/m2 and high-dose cyclophosphamide (HD-CPM) 140 mg/kg, followed by 2 courses of ifosfamide, carboplatin and etoposide (ICE) every 28 days. After surgery on primary tumour, a fifth course with vincristine, doxorubicin and CPM was given, followed by high-dose chemotherapy with stem cell support. Response was assessed in accordance with the International Neuroblastoma Response Criteria. Results: Of 35 consecutive patients, 33 had metastatic disease. The median length of induction phase was 133 days (range 91-207) and time to high-dose chemotherapy was 208 days (range 156-285). The median tumour volume reduction was 55{\%} after two HD-TPT/HD-CPM courses and 80{\%} after four courses. Radical surgery was performed in 16/27 patients after chemotherapy. After the fifth course, 29/34 patients (85{\%}) had achieved a partial remission (12) or a CR/very good partial remission (17). CR of metastases was achieved in 13/32 (41{\%}) and bone marrow was in complete remission in 16/24 patients (67{\%}). Grade 4 neutropenia and/or thrombocytopenia occurred in 100{\%} of HD-TPT/HD-CPM and in 95{\%} of ICE courses, while non-haematological toxicities were manageable. Conclusions: These data indicate that our induction regimen is feasible and well tolerated. A major response rate of 85{\%} with 41{\%} complete metastatic response confirms this regimen as effective induction in high-risk neuroblastoma.",
keywords = "Children, Induction, Metastasis, Neuroblastoma, Remission, Topotecan",
author = "{De Ioris}, {Maria Antonietta} and Aurora Castellano and Ilaria Ilari and Garganese, {Maria Carmen} and Gianluigi Natali and Alessandro Inserra and Vito, {Rita De} and Lucilla Rav and Pasquale, {Maria Debora De} and Franco Locatelli and Alberto Donfrancesco and Alessandro Jenkner",
year = "2011",
month = "3",
doi = "10.1016/j.ejca.2010.10.023",
language = "English",
volume = "47",
pages = "572--578",
journal = "European Journal of Cancer",
issn = "0959-8049",
publisher = "Elsevier Ltd",
number = "4",

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TY - JOUR

T1 - Short topotecan-based induction regimen in newly diagnosed high-risk neuroblastoma

AU - De Ioris, Maria Antonietta

AU - Castellano, Aurora

AU - Ilari, Ilaria

AU - Garganese, Maria Carmen

AU - Natali, Gianluigi

AU - Inserra, Alessandro

AU - Vito, Rita De

AU - Rav, Lucilla

AU - Pasquale, Maria Debora De

AU - Locatelli, Franco

AU - Donfrancesco, Alberto

AU - Jenkner, Alessandro

PY - 2011/3

Y1 - 2011/3

N2 - Purpose: Topotecan is an active drug in relapsed neuroblastoma. We investigated the efficacy and toxicity of a topotecan-based induction regimen in newly diagnosed neuroblastoma. Methods: Patients older than 1 year with either metastatic or localised stage 2-3 MYCN-amplified neuroblastoma received 2 courses of high-dose topotecan (HD-TPT) 6 mg/m2 and high-dose cyclophosphamide (HD-CPM) 140 mg/kg, followed by 2 courses of ifosfamide, carboplatin and etoposide (ICE) every 28 days. After surgery on primary tumour, a fifth course with vincristine, doxorubicin and CPM was given, followed by high-dose chemotherapy with stem cell support. Response was assessed in accordance with the International Neuroblastoma Response Criteria. Results: Of 35 consecutive patients, 33 had metastatic disease. The median length of induction phase was 133 days (range 91-207) and time to high-dose chemotherapy was 208 days (range 156-285). The median tumour volume reduction was 55% after two HD-TPT/HD-CPM courses and 80% after four courses. Radical surgery was performed in 16/27 patients after chemotherapy. After the fifth course, 29/34 patients (85%) had achieved a partial remission (12) or a CR/very good partial remission (17). CR of metastases was achieved in 13/32 (41%) and bone marrow was in complete remission in 16/24 patients (67%). Grade 4 neutropenia and/or thrombocytopenia occurred in 100% of HD-TPT/HD-CPM and in 95% of ICE courses, while non-haematological toxicities were manageable. Conclusions: These data indicate that our induction regimen is feasible and well tolerated. A major response rate of 85% with 41% complete metastatic response confirms this regimen as effective induction in high-risk neuroblastoma.

AB - Purpose: Topotecan is an active drug in relapsed neuroblastoma. We investigated the efficacy and toxicity of a topotecan-based induction regimen in newly diagnosed neuroblastoma. Methods: Patients older than 1 year with either metastatic or localised stage 2-3 MYCN-amplified neuroblastoma received 2 courses of high-dose topotecan (HD-TPT) 6 mg/m2 and high-dose cyclophosphamide (HD-CPM) 140 mg/kg, followed by 2 courses of ifosfamide, carboplatin and etoposide (ICE) every 28 days. After surgery on primary tumour, a fifth course with vincristine, doxorubicin and CPM was given, followed by high-dose chemotherapy with stem cell support. Response was assessed in accordance with the International Neuroblastoma Response Criteria. Results: Of 35 consecutive patients, 33 had metastatic disease. The median length of induction phase was 133 days (range 91-207) and time to high-dose chemotherapy was 208 days (range 156-285). The median tumour volume reduction was 55% after two HD-TPT/HD-CPM courses and 80% after four courses. Radical surgery was performed in 16/27 patients after chemotherapy. After the fifth course, 29/34 patients (85%) had achieved a partial remission (12) or a CR/very good partial remission (17). CR of metastases was achieved in 13/32 (41%) and bone marrow was in complete remission in 16/24 patients (67%). Grade 4 neutropenia and/or thrombocytopenia occurred in 100% of HD-TPT/HD-CPM and in 95% of ICE courses, while non-haematological toxicities were manageable. Conclusions: These data indicate that our induction regimen is feasible and well tolerated. A major response rate of 85% with 41% complete metastatic response confirms this regimen as effective induction in high-risk neuroblastoma.

KW - Children

KW - Induction

KW - Metastasis

KW - Neuroblastoma

KW - Remission

KW - Topotecan

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