- 作者：Angela Di Giannatale ; Nathalie Dias-Gastellier ; Annick Devos ; Kieran Mc Hugh ; Ariane Boubaker ; Frederic Courbon ; Arnaud Verschuur ; St茅phane Ducassoul ; Katty Malekzadeh ; Michela Casanova ; Loredana Amoroso ; Pascal Chastagner ; Christian M. Zwaan ; Caroline Munzer ; Isabelle Aerts ; Judith L ; man-Parker ; Riccardo Riccardi ; Marie-Cecile Le Deley ; Birgit Geoerger ; Herv茅 Rubie
- 关键词：Paediatrics ; Temozolomide ; Topotecan ; Phase II ; Neuroblastoma
- 刊名：European Journal of Cancer
- 出版年：January, 2014
- 年：2014
- 卷：50
- 期：1
- 页码：170-177
- 全文大小：741 K
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.