Topotecan-Vincristine-Doxorubicin in Stage 4 High-Risk Neuroblastoma Patients Failing to Achieve a Complete Metastatic Response to Rapid COJEC: A SIOPEN Study

SIOPEN Group

Research output: Contribution to journalArticle

Abstract

PURPOSE: Metastatic response to induction therapy for high-risk neuroblastoma is a prognostic factor. In the International Society of Paediatric Oncology Europe Neuroblastoma (SIOPEN) HR-NBL-1 protocol, only patients with metastatic complete response (CR) or partial response (PR) with ≤ three abnormal skeletal areas on iodine 123-metaiodobenzylguanidine ([123I]mIBG) scintigraphy and no bone marrow disease proceed to high dose therapy (HDT). In this study, topotecan-vincristine-doxorubicin (TVD) was evaluated in patients failing to achieve these criteria, with the aim of improving the metastatic response rate.

MATERIALS AND METHODS: Patients with metastatic high-risk neuroblastoma who had not achieved the SIOPEN criteria for HDT after induction received two courses of topotecan 1.5 mg/m2/day for 5 days, followed by a 48-hour infusion of vincristine, 2 mg/m2, and doxorubicin, 45 mg/m2.

RESULTS: Sixty-three patients were eligible and evaluable. Following two courses of TVD, four (6.4%) patients had an overall CR, while 28 (44.4%) had a PR with a combined response rate of 50.8% (95% confidence interval [CI], 37.9 to 63.6). Of these, 23 patients achieved a metastatic CR or a PR with ≤ 3 mIBG skeletal areas and no bone marrow disease (36.5%; 95% CI, 24.7 to 49.6) and were eligible to receive HDT. Toxicity was mostly haematological, affecting 106 of the 126 courses (84.1%; 95% CI, 76.5 to 90.0), and dose reduction was necessary in six patients. Stomatitis was the second most common nonhematological toxicity, occurring in 20 patients (31.7%).

CONCLUSION: TVD was effective in improving the response rate of high-risk neuroblastoma patients after induction with COJEC enabling them to proceed to HDT. However, the long-term benefits of TVD needs to be determined in randomized clinical trials.

Original languageEnglish
Pages (from-to)148-155
Number of pages8
JournalCancer Research and Treatment
Volume50
Issue number1
DOIs
Publication statusPublished - Jan 2018

Fingerprint

Topotecan
Vincristine
Neuroblastoma
Doxorubicin
Pediatrics
Bone Marrow Diseases
Confidence Intervals
Therapeutics
Stomatitis
Radionuclide Imaging
Iodine
Randomized Controlled Trials

Keywords

  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols/therapeutic use
  • Doxorubicin/administration & dosage
  • Female
  • Humans
  • Male
  • Middle Aged
  • Neoplasm Staging
  • Neuroblastoma/drug therapy
  • Risk Factors
  • Topoisomerase I Inhibitors/administration & dosage
  • Topotecan/administration & dosage
  • Vincristine/administration & dosage

Cite this

@article{a61a52a16f4a48e4b3703a9fd1244530,
title = "Topotecan-Vincristine-Doxorubicin in Stage 4 High-Risk Neuroblastoma Patients Failing to Achieve a Complete Metastatic Response to Rapid COJEC: A SIOPEN Study",
abstract = "PURPOSE: Metastatic response to induction therapy for high-risk neuroblastoma is a prognostic factor. In the International Society of Paediatric Oncology Europe Neuroblastoma (SIOPEN) HR-NBL-1 protocol, only patients with metastatic complete response (CR) or partial response (PR) with ≤ three abnormal skeletal areas on iodine 123-metaiodobenzylguanidine ([123I]mIBG) scintigraphy and no bone marrow disease proceed to high dose therapy (HDT). In this study, topotecan-vincristine-doxorubicin (TVD) was evaluated in patients failing to achieve these criteria, with the aim of improving the metastatic response rate.MATERIALS AND METHODS: Patients with metastatic high-risk neuroblastoma who had not achieved the SIOPEN criteria for HDT after induction received two courses of topotecan 1.5 mg/m2/day for 5 days, followed by a 48-hour infusion of vincristine, 2 mg/m2, and doxorubicin, 45 mg/m2.RESULTS: Sixty-three patients were eligible and evaluable. Following two courses of TVD, four (6.4{\%}) patients had an overall CR, while 28 (44.4{\%}) had a PR with a combined response rate of 50.8{\%} (95{\%} confidence interval [CI], 37.9 to 63.6). Of these, 23 patients achieved a metastatic CR or a PR with ≤ 3 mIBG skeletal areas and no bone marrow disease (36.5{\%}; 95{\%} CI, 24.7 to 49.6) and were eligible to receive HDT. Toxicity was mostly haematological, affecting 106 of the 126 courses (84.1{\%}; 95{\%} CI, 76.5 to 90.0), and dose reduction was necessary in six patients. Stomatitis was the second most common nonhematological toxicity, occurring in 20 patients (31.7{\%}).CONCLUSION: TVD was effective in improving the response rate of high-risk neuroblastoma patients after induction with COJEC enabling them to proceed to HDT. However, the long-term benefits of TVD needs to be determined in randomized clinical trials.",
keywords = "Adult, Aged, Antineoplastic Combined Chemotherapy Protocols/therapeutic use, Doxorubicin/administration & dosage, Female, Humans, Male, Middle Aged, Neoplasm Staging, Neuroblastoma/drug therapy, Risk Factors, Topoisomerase I Inhibitors/administration & dosage, Topotecan/administration & dosage, Vincristine/administration & dosage",
author = "{SIOPEN Group} and Loredana Amoroso and Giovanni Erminio and Guy Makin and Pearson, {Andrew D J} and Penelope Brock and Dominique Valteau-Couanet and Victoria Castel and Marl{\`e}ne Pasquet and Genevieve Laureys and Caroline Thomas and Roberto Luksch and Ruth Ladenstein and Riccardo Haupt and Alberto Garaventa",
year = "2018",
month = "1",
doi = "10.4143/crt.2016.511",
language = "English",
volume = "50",
pages = "148--155",
journal = "Cancer Research and Treatment",
issn = "1598-2998",
publisher = "Korean Cancer Association",
number = "1",

}

TY - JOUR

T1 - Topotecan-Vincristine-Doxorubicin in Stage 4 High-Risk Neuroblastoma Patients Failing to Achieve a Complete Metastatic Response to Rapid COJEC

T2 - A SIOPEN Study

AU - SIOPEN Group

AU - Amoroso, Loredana

AU - Erminio, Giovanni

AU - Makin, Guy

AU - Pearson, Andrew D J

AU - Brock, Penelope

AU - Valteau-Couanet, Dominique

AU - Castel, Victoria

AU - Pasquet, Marlène

AU - Laureys, Genevieve

AU - Thomas, Caroline

AU - Luksch, Roberto

AU - Ladenstein, Ruth

AU - Haupt, Riccardo

AU - Garaventa, Alberto

PY - 2018/1

Y1 - 2018/1

N2 - PURPOSE: Metastatic response to induction therapy for high-risk neuroblastoma is a prognostic factor. In the International Society of Paediatric Oncology Europe Neuroblastoma (SIOPEN) HR-NBL-1 protocol, only patients with metastatic complete response (CR) or partial response (PR) with ≤ three abnormal skeletal areas on iodine 123-metaiodobenzylguanidine ([123I]mIBG) scintigraphy and no bone marrow disease proceed to high dose therapy (HDT). In this study, topotecan-vincristine-doxorubicin (TVD) was evaluated in patients failing to achieve these criteria, with the aim of improving the metastatic response rate.MATERIALS AND METHODS: Patients with metastatic high-risk neuroblastoma who had not achieved the SIOPEN criteria for HDT after induction received two courses of topotecan 1.5 mg/m2/day for 5 days, followed by a 48-hour infusion of vincristine, 2 mg/m2, and doxorubicin, 45 mg/m2.RESULTS: Sixty-three patients were eligible and evaluable. Following two courses of TVD, four (6.4%) patients had an overall CR, while 28 (44.4%) had a PR with a combined response rate of 50.8% (95% confidence interval [CI], 37.9 to 63.6). Of these, 23 patients achieved a metastatic CR or a PR with ≤ 3 mIBG skeletal areas and no bone marrow disease (36.5%; 95% CI, 24.7 to 49.6) and were eligible to receive HDT. Toxicity was mostly haematological, affecting 106 of the 126 courses (84.1%; 95% CI, 76.5 to 90.0), and dose reduction was necessary in six patients. Stomatitis was the second most common nonhematological toxicity, occurring in 20 patients (31.7%).CONCLUSION: TVD was effective in improving the response rate of high-risk neuroblastoma patients after induction with COJEC enabling them to proceed to HDT. However, the long-term benefits of TVD needs to be determined in randomized clinical trials.

AB - PURPOSE: Metastatic response to induction therapy for high-risk neuroblastoma is a prognostic factor. In the International Society of Paediatric Oncology Europe Neuroblastoma (SIOPEN) HR-NBL-1 protocol, only patients with metastatic complete response (CR) or partial response (PR) with ≤ three abnormal skeletal areas on iodine 123-metaiodobenzylguanidine ([123I]mIBG) scintigraphy and no bone marrow disease proceed to high dose therapy (HDT). In this study, topotecan-vincristine-doxorubicin (TVD) was evaluated in patients failing to achieve these criteria, with the aim of improving the metastatic response rate.MATERIALS AND METHODS: Patients with metastatic high-risk neuroblastoma who had not achieved the SIOPEN criteria for HDT after induction received two courses of topotecan 1.5 mg/m2/day for 5 days, followed by a 48-hour infusion of vincristine, 2 mg/m2, and doxorubicin, 45 mg/m2.RESULTS: Sixty-three patients were eligible and evaluable. Following two courses of TVD, four (6.4%) patients had an overall CR, while 28 (44.4%) had a PR with a combined response rate of 50.8% (95% confidence interval [CI], 37.9 to 63.6). Of these, 23 patients achieved a metastatic CR or a PR with ≤ 3 mIBG skeletal areas and no bone marrow disease (36.5%; 95% CI, 24.7 to 49.6) and were eligible to receive HDT. Toxicity was mostly haematological, affecting 106 of the 126 courses (84.1%; 95% CI, 76.5 to 90.0), and dose reduction was necessary in six patients. Stomatitis was the second most common nonhematological toxicity, occurring in 20 patients (31.7%).CONCLUSION: TVD was effective in improving the response rate of high-risk neuroblastoma patients after induction with COJEC enabling them to proceed to HDT. However, the long-term benefits of TVD needs to be determined in randomized clinical trials.

KW - Adult

KW - Aged

KW - Antineoplastic Combined Chemotherapy Protocols/therapeutic use

KW - Doxorubicin/administration & dosage

KW - Female

KW - Humans

KW - Male

KW - Middle Aged

KW - Neoplasm Staging

KW - Neuroblastoma/drug therapy

KW - Risk Factors

KW - Topoisomerase I Inhibitors/administration & dosage

KW - Topotecan/administration & dosage

KW - Vincristine/administration & dosage

U2 - 10.4143/crt.2016.511

DO - 10.4143/crt.2016.511

M3 - Article

C2 - 28324923

VL - 50

SP - 148

EP - 155

JO - Cancer Research and Treatment

JF - Cancer Research and Treatment

SN - 1598-2998

IS - 1

ER -