Phase II study of temozolomide and topotecan (TOTEM) in children with relapsed or refractory extracranial and central nervous system tumors including medulloblastoma with post hoc Bayesian analysis: A European ITCC study

Aim To assess objective response after two cycles of temozolomide and topotecan (TOTEM) in children with refractory or relapsed miscellaneous extracranial solid and central nervous system (CNS) tumors, including medulloblastoma and primitive neuroectodermal tumors (PNET). Procedure Multicenter, nonr...

Full description

Saved in:
Bibliographic Details
Published in:Pediatric blood & cancer 2020-01, Vol.67 (1), p.e28032-n/a
Main Authors: Le Teuff, Gwénaël, Castaneda‐Heredia, Alicia, Dufour, Christelle, Jaspan, Timothy, Calmon, Raphael, Devos, Annick, McHugh, Kieran, Leblond, Pierre, Frappaz, Didier, Aerts, Isabelle, Zwaan, Christian M., Ducassou, Stéphane, Chastagner, Pascal, Verschuur, Arnauld, Corradini, Nadège, Casanova, Michela, Rubie, Hervé, Riccardi, Riccardo, Le Deley, Marie‐Cecile, Vassal, Gilles, Geoerger, Birgit
Format: Article
Language:English
Subjects:
Adolescent
Adult
Antineoplastic Combined Chemotherapy Protocols - therapeutic use
Bayes Theorem
Bayesian analysis
Brain cancer
Brain tumors
Central nervous system
Central Nervous System Neoplasms - drug therapy
Central Nervous System Neoplasms - pathology
Cerebellar Neoplasms - drug therapy
Cerebellar Neoplasms - pathology
Child
Child, Preschool
Children
Drug Resistance, Neoplasm - drug effects
Female
Follow-Up Studies
Glioma
Hematology
Humans
Infant
Life Sciences
Male
Medical treatment
Medulloblastoma
Medulloblastoma - drug therapy
Medulloblastoma - pathology
Neoplasm Recurrence, Local - drug therapy
Neoplasm Recurrence, Local - pathology
Nervous system
Nervous system diseases
Neuroectodermal Tumors, Primitive - drug therapy
Neuroectodermal Tumors, Primitive - pathology
Oncology
Oral administration
pediatric solid tumors
Pediatrics
Prognosis
Salvage Therapy
Solid tumors
Survival Rate
Temozolomide
Temozolomide - administration & dosage
Topotecan
Topotecan - administration & dosage
Toxicity
Tumors
Young Adult
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Aim To assess objective response after two cycles of temozolomide and topotecan (TOTEM) in children with refractory or relapsed miscellaneous extracranial solid and central nervous system (CNS) tumors, including medulloblastoma and primitive neuroectodermal tumors (PNET). Procedure Multicenter, nonrandomized, phase 2 basket trial including children with solid tumors, completed by a one‐stage design confirmatory cohort for medulloblastoma, and an exploratory cohort for PNET. Main eligibility criteria were refractory/relapsed measurable disease and no more than two prior treatment lines. Temozolomide was administered orally at 150 mg/m2/day followed by topotecan at 0.75 mg/m2/day intravenously for five consecutive days every 28 days. Tumor response was assessed every two cycles according to WHO criteria and reviewed independently. Results Thirty‐two patients were enrolled and treated in the miscellaneous solid tumor and 33 in the CNS strata; 20 patients with medulloblastoma and six with PNET were included in the expansion cohorts. The median age at inclusion was 10.0 years (range, 0.9‐20.9). In the basket cohorts, confirmed complete and partial responses were observed in one glioma, four medulloblastoma, and one PNET, leading to the extension. The overall objective response rate (ORR) in medulloblastoma was 28% (95% CI, 12.7‐47.2) with 1/29 complete and 7/29 partial responses, those for PNET 10% (95% CI, 0.3‐44.5). Post hoc Bayesian analysis estimates that the true ORR in medulloblastoma is probably between 20% and 30% and below 20% in PNET. The most common treatment‐related toxicities of the combination therapy were hematologic. Conclusions Temozolomide‐topotecan results in significant ORR in children with recurrent and refractory medulloblastoma with a favorable toxicity profile.
ISSN:1545-5009
1545-5017
DOI:10.1002/pbc.28032