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
N1 - Funding Information:
Supported by grants from ‘Enfants et Santé’ and the ‘Société Française des Cancers de l’Enfant’, the ‘Association Régionale Midi-Pyrénées pour l’Etude et le Traitement des Cancers de l’Enfant’ (ARETCE), Glaxo-Smith Kline, France and the KiKa Foundation for The Netherlands.
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
U2 - 10.1016/j.ejca.2013.08.012
DO - 10.1016/j.ejca.2013.08.012
M3 - Article
C2 - 24021349
AN - SCOPUS:84891624988
SN - 0959-8049
VL - 50
SP - 170
EP - 177
JO - European Journal of Cancer
JF - European Journal of Cancer
IS - 1
ER -