Phase II study of temozolomide in combination with topotecan (TOTEM) in relapsed or refractory neuroblastoma: A European Innovative Therapies for Children with Cancer-SIOP-European Neuroblastoma study

Angela Di Giannatale, Nathalie Dias-Gastellier, Annick Devos, Kieran Mc Hugh, Ariane Boubaker, Frederic Courbon, Arnaud Verschuur, Stéphane Ducassoul, Katty Malekzadeh, Michela Casanova, Loredana Amoroso, Pascal Chastagner, Christian M. Zwaan, Caroline Munzer, Isabelle Aerts, Judith Landman-Parker, Riccardo Riccardi, Marie Cecile Le Deley, Birgit Geoerger, Hervé Rubie

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

Purpose To assess objective response rate (ORR) after two cycles of temozolomide in combination with topotecan (TOTEM) in children with refractory or relapsed neuroblastoma. Patients and Methods This multicenter, non-randomised, phase II study included children with neuroblastoma according to a two-stage Simon design. Eligibility criteria included relapsed or refractory, measurable or metaiodobenzylguanidine (mIBG) evaluable disease, no more than two lines of prior treatment. Temozolomide was administered orally at 150 mg/m2 followed by topotecan at 0.75 mg/m2 intravenously for five consecutive days every 28 days. Tumour response was assessed every two cycles according to International Neuroblastoma Response Criteria (INRC), and reviewed independently. Results Thirty-eight patients were enroled and treated in 15 European centres with a median age of 5.4 years. Partial tumour response after two cycles was observed in 7 out of 38 evaluable patients [ORR 18%, 95% confidence interval (CI) 8-34%]. The best ORR whatever the time of evaluation was 24% (95% CI, 11-40%) with a median response duration of 8.5 months. Tumour control rate (complete response (CR) + partial response (PR) + mixed response (MR) + stable disease (SD)) was 68% (95% CI, 63-90%). The 12-months Progression-Free and Overall Survival were 42% and 58% respectively. Among 213 treatment cycles (median 4, range 1-12 per patient) the most common treatment-related toxicities were haematologic. Grade 3/4 neutropenia occurred in 62% of courses in 89% of patients, grade 3/4 thrombocytopenia in 47% of courses in 71% of patients; three patients (8%) had febrile neutropenia. Conclusion Temozolomide-Topotecan combination results in very encouraging ORR and tumour control in children with heavily pretreated recurrent and refractory neuroblastoma with favourable toxicity profile.

Original languageEnglish
Pages (from-to)170-177
Number of pages8
JournalEuropean Journal of Cancer
Volume50
Issue number1
DOIs
Publication statusPublished - Jan 2014

Fingerprint

temozolomide
Topotecan
Investigational Therapies
Neuroblastoma
Neoplasms
Confidence Intervals
Febrile Neutropenia
Neutropenia
Disease-Free Survival
Therapeutics

Keywords

  • Neuroblastoma
  • Paediatrics
  • Phase II
  • Temozolomide
  • Topotecan

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Phase II study of temozolomide in combination with topotecan (TOTEM) in relapsed or refractory neuroblastoma : A European Innovative Therapies for Children with Cancer-SIOP-European Neuroblastoma study. / Di Giannatale, Angela; Dias-Gastellier, Nathalie; Devos, Annick; Mc Hugh, Kieran; Boubaker, Ariane; Courbon, Frederic; Verschuur, Arnaud; Ducassoul, Stéphane; Malekzadeh, Katty; Casanova, Michela; Amoroso, Loredana; Chastagner, Pascal; Zwaan, Christian M.; Munzer, Caroline; Aerts, Isabelle; Landman-Parker, Judith; Riccardi, Riccardo; Le Deley, Marie Cecile; Geoerger, Birgit; Rubie, Hervé.

In: European Journal of Cancer, Vol. 50, No. 1, 01.2014, p. 170-177.

Research output: Contribution to journalArticle

Di Giannatale, A, Dias-Gastellier, N, Devos, A, Mc Hugh, K, Boubaker, A, Courbon, F, Verschuur, A, Ducassoul, S, Malekzadeh, K, Casanova, M, Amoroso, L, Chastagner, P, Zwaan, CM, Munzer, C, Aerts, I, Landman-Parker, J, Riccardi, R, Le Deley, MC, Geoerger, B & Rubie, H 2014, 'Phase II study of temozolomide in combination with topotecan (TOTEM) in relapsed or refractory neuroblastoma: A European Innovative Therapies for Children with Cancer-SIOP-European Neuroblastoma study', European Journal of Cancer, vol. 50, no. 1, pp. 170-177. https://doi.org/10.1016/j.ejca.2013.08.012
Di Giannatale, Angela ; Dias-Gastellier, Nathalie ; Devos, Annick ; Mc Hugh, Kieran ; Boubaker, Ariane ; Courbon, Frederic ; Verschuur, Arnaud ; Ducassoul, Stéphane ; Malekzadeh, Katty ; Casanova, Michela ; Amoroso, Loredana ; Chastagner, Pascal ; Zwaan, Christian M. ; Munzer, Caroline ; Aerts, Isabelle ; Landman-Parker, Judith ; Riccardi, Riccardo ; Le Deley, Marie Cecile ; Geoerger, Birgit ; Rubie, Hervé. / Phase II study of temozolomide in combination with topotecan (TOTEM) in relapsed or refractory neuroblastoma : A European Innovative Therapies for Children with Cancer-SIOP-European Neuroblastoma study. In: European Journal of Cancer. 2014 ; Vol. 50, No. 1. pp. 170-177.
@article{1485f3ac6fa142c39697f75302db6d73,
title = "Phase II study of temozolomide in combination with topotecan (TOTEM) in relapsed or refractory neuroblastoma: A European Innovative Therapies for Children with Cancer-SIOP-European Neuroblastoma study",
abstract = "Purpose To assess objective response rate (ORR) after two cycles of temozolomide in combination with topotecan (TOTEM) in children with refractory or relapsed neuroblastoma. Patients and Methods This multicenter, non-randomised, phase II study included children with neuroblastoma according to a two-stage Simon design. Eligibility criteria included relapsed or refractory, measurable or metaiodobenzylguanidine (mIBG) evaluable disease, no more than two lines of prior treatment. Temozolomide was administered orally at 150 mg/m2 followed by topotecan at 0.75 mg/m2 intravenously for five consecutive days every 28 days. Tumour response was assessed every two cycles according to International Neuroblastoma Response Criteria (INRC), and reviewed independently. Results Thirty-eight patients were enroled and treated in 15 European centres with a median age of 5.4 years. Partial tumour response after two cycles was observed in 7 out of 38 evaluable patients [ORR 18{\%}, 95{\%} confidence interval (CI) 8-34{\%}]. The best ORR whatever the time of evaluation was 24{\%} (95{\%} CI, 11-40{\%}) with a median response duration of 8.5 months. Tumour control rate (complete response (CR) + partial response (PR) + mixed response (MR) + stable disease (SD)) was 68{\%} (95{\%} CI, 63-90{\%}). The 12-months Progression-Free and Overall Survival were 42{\%} and 58{\%} respectively. Among 213 treatment cycles (median 4, range 1-12 per patient) the most common treatment-related toxicities were haematologic. Grade 3/4 neutropenia occurred in 62{\%} of courses in 89{\%} of patients, grade 3/4 thrombocytopenia in 47{\%} of courses in 71{\%} of patients; three patients (8{\%}) had febrile neutropenia. Conclusion Temozolomide-Topotecan combination results in very encouraging ORR and tumour control in children with heavily pretreated recurrent and refractory neuroblastoma with favourable toxicity profile.",
keywords = "Neuroblastoma, Paediatrics, Phase II, Temozolomide, Topotecan",
author = "{Di Giannatale}, Angela and Nathalie Dias-Gastellier and Annick Devos and {Mc Hugh}, Kieran and Ariane Boubaker and Frederic Courbon and Arnaud Verschuur and St{\'e}phane Ducassoul and Katty Malekzadeh and Michela Casanova and Loredana Amoroso and Pascal Chastagner and Zwaan, {Christian M.} and Caroline Munzer and Isabelle Aerts and Judith Landman-Parker and Riccardo Riccardi and {Le Deley}, {Marie Cecile} and Birgit Geoerger and Herv{\'e} Rubie",
year = "2014",
month = "1",
doi = "10.1016/j.ejca.2013.08.012",
language = "English",
volume = "50",
pages = "170--177",
journal = "European Journal of Cancer",
issn = "0959-8049",
publisher = "Elsevier Ltd",
number = "1",

}

TY - JOUR

T1 - Phase II study of temozolomide in combination with topotecan (TOTEM) in relapsed or refractory neuroblastoma

T2 - A European Innovative Therapies for Children with Cancer-SIOP-European Neuroblastoma study

AU - Di Giannatale, Angela

AU - Dias-Gastellier, Nathalie

AU - Devos, Annick

AU - Mc Hugh, Kieran

AU - Boubaker, Ariane

AU - Courbon, Frederic

AU - Verschuur, Arnaud

AU - Ducassoul, Stéphane

AU - Malekzadeh, Katty

AU - Casanova, Michela

AU - Amoroso, Loredana

AU - Chastagner, Pascal

AU - Zwaan, Christian M.

AU - Munzer, Caroline

AU - Aerts, Isabelle

AU - Landman-Parker, Judith

AU - Riccardi, Riccardo

AU - Le Deley, Marie Cecile

AU - Geoerger, Birgit

AU - Rubie, Hervé

PY - 2014/1

Y1 - 2014/1

N2 - Purpose To assess objective response rate (ORR) after two cycles of temozolomide in combination with topotecan (TOTEM) in children with refractory or relapsed neuroblastoma. Patients and Methods This multicenter, non-randomised, phase II study included children with neuroblastoma according to a two-stage Simon design. Eligibility criteria included relapsed or refractory, measurable or metaiodobenzylguanidine (mIBG) evaluable disease, no more than two lines of prior treatment. Temozolomide was administered orally at 150 mg/m2 followed by topotecan at 0.75 mg/m2 intravenously for five consecutive days every 28 days. Tumour response was assessed every two cycles according to International Neuroblastoma Response Criteria (INRC), and reviewed independently. Results Thirty-eight patients were enroled and treated in 15 European centres with a median age of 5.4 years. Partial tumour response after two cycles was observed in 7 out of 38 evaluable patients [ORR 18%, 95% confidence interval (CI) 8-34%]. The best ORR whatever the time of evaluation was 24% (95% CI, 11-40%) with a median response duration of 8.5 months. Tumour control rate (complete response (CR) + partial response (PR) + mixed response (MR) + stable disease (SD)) was 68% (95% CI, 63-90%). The 12-months Progression-Free and Overall Survival were 42% and 58% respectively. Among 213 treatment cycles (median 4, range 1-12 per patient) the most common treatment-related toxicities were haematologic. Grade 3/4 neutropenia occurred in 62% of courses in 89% of patients, grade 3/4 thrombocytopenia in 47% of courses in 71% of patients; three patients (8%) had febrile neutropenia. Conclusion Temozolomide-Topotecan combination results in very encouraging ORR and tumour control in children with heavily pretreated recurrent and refractory neuroblastoma with favourable toxicity profile.

AB - Purpose To assess objective response rate (ORR) after two cycles of temozolomide in combination with topotecan (TOTEM) in children with refractory or relapsed neuroblastoma. Patients and Methods This multicenter, non-randomised, phase II study included children with neuroblastoma according to a two-stage Simon design. Eligibility criteria included relapsed or refractory, measurable or metaiodobenzylguanidine (mIBG) evaluable disease, no more than two lines of prior treatment. Temozolomide was administered orally at 150 mg/m2 followed by topotecan at 0.75 mg/m2 intravenously for five consecutive days every 28 days. Tumour response was assessed every two cycles according to International Neuroblastoma Response Criteria (INRC), and reviewed independently. Results Thirty-eight patients were enroled and treated in 15 European centres with a median age of 5.4 years. Partial tumour response after two cycles was observed in 7 out of 38 evaluable patients [ORR 18%, 95% confidence interval (CI) 8-34%]. The best ORR whatever the time of evaluation was 24% (95% CI, 11-40%) with a median response duration of 8.5 months. Tumour control rate (complete response (CR) + partial response (PR) + mixed response (MR) + stable disease (SD)) was 68% (95% CI, 63-90%). The 12-months Progression-Free and Overall Survival were 42% and 58% respectively. Among 213 treatment cycles (median 4, range 1-12 per patient) the most common treatment-related toxicities were haematologic. Grade 3/4 neutropenia occurred in 62% of courses in 89% of patients, grade 3/4 thrombocytopenia in 47% of courses in 71% of patients; three patients (8%) had febrile neutropenia. Conclusion Temozolomide-Topotecan combination results in very encouraging ORR and tumour control in children with heavily pretreated recurrent and refractory neuroblastoma with favourable toxicity profile.

KW - Neuroblastoma

KW - Paediatrics

KW - Phase II

KW - Temozolomide

KW - Topotecan

UR - http://www.scopus.com/inward/record.url?scp=84891624988&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84891624988&partnerID=8YFLogxK

U2 - 10.1016/j.ejca.2013.08.012

DO - 10.1016/j.ejca.2013.08.012

M3 - Article

C2 - 24021349

AN - SCOPUS:84891624988

VL - 50

SP - 170

EP - 177

JO - European Journal of Cancer

JF - European Journal of Cancer

SN - 0959-8049

IS - 1

ER -