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.
Adolescent
Adult
Antineoplastic Combined Chemotherapy Protocols
/ therapeutic use
Bayes Theorem
Central Nervous System Neoplasms
/ drug therapy
Cerebellar Neoplasms
/ drug therapy
Child
Child, Preschool
Drug Resistance, Neoplasm
/ drug effects
Female
Follow-Up Studies
Humans
Infant
Male
Medulloblastoma
/ drug therapy
Neoplasm Recurrence, Local
/ drug therapy
Neuroectodermal Tumors, Primitive
/ drug therapy
Prognosis
Salvage Therapy
Survival Rate
Temozolomide
/ administration & dosage
Topotecan
/ administration & dosage
Young Adult
Bayesian analysis
medulloblastoma
pediatric solid tumors
temozolomide
topotecan
Journal
Pediatric blood & cancer
ISSN: 1545-5017
Titre abrégé: Pediatr Blood Cancer
Pays: United States
ID NLM: 101186624
Informations de publication
Date de publication:
01 2020
01 2020
Historique:
received:
20
03
2019
revised:
19
09
2019
accepted:
23
09
2019
pubmed:
9
10
2019
medline:
10
4
2020
entrez:
10
10
2019
Statut:
ppublish
Résumé
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). 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/m 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. Temozolomide-topotecan results in significant ORR in children with recurrent and refractory medulloblastoma with a favorable toxicity profile.
Substances chimiques
Topotecan
7M7YKX2N15
Temozolomide
YF1K15M17Y
Types de publication
Clinical Trial, Phase II
Journal Article
Multicenter Study
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e28032Informations de copyright
© 2019 Wiley Periodicals, Inc.
Références
Smith MA, Seibel NL, Altekruse SF, et al. Outcomes for children and adolescents with cancer: challenges for the twenty-first century. J Clin Oncol. 2010;28:2625-2634.
Mutter N, Stupp R. Temozolomide: a milestone in neuro-oncology and beyond? Expert Rev Anticancer Ther. 2006;6:1187-1204.
Friedman HS, Kerby T, Calvert H, et al. Temozolomide and treatment of malignant glioma. Clin Cancer Res. 2000;6:2585-2597.
Lashford LS, Thiesse P, Jouvet A, et al. Temozolomide in malignant gliomas of childhood: a United Kingdom Children's Cancer Study Group and French Society for Pediatric Oncology Intergroup Study. J Clin Oncol. 2002;20:4684-4691.
Brada M, Hoang-Xuan K, Rampling R, et al. Multicenter phase II trial of temozolomide in patients with glioblastoma multiforme at first relapse. Ann Oncol. 2001;12:259-266.
Nicholson HS, Krailo M, Ames MM, et al. Phase I study of temozolomide in children and adolescents with recurrent solid tumors: a report from the Children's Cancer Group. J Clin Oncol. 1998;16:3037-3043.
De Sio L, Milano GM, Castellano A, et al. Temozolomide in resistant or relapsed pediatric solid tumors. Pediatr Blood Cancer. 2006;47:30-36.
Estlin EJ, Lashford L, Ablett S, et al. Phase I study of temozolomide in paediatric patients with advanced cancer. United Kingdom Children's Cancer Study Group. Br J Cancer. 1998;78:652-661.
Rubie H, Chisholm J, Defachelles AS, et al. Phase II study of temozolomide in relapsed or refractory high-risk neuroblastoma: a joint Société Française des Cancers de l'Enfant and United Kingdom Children Cancer Study Group-New Agents Group Study. J Clin Oncol. 2006;24:5259-5264.
Nicholson HS, Kretschmar CS, Krailo M, et al. Phase 2 study of temozolomide in children and adolescents with recurrent central nervous system tumors: a report from the Children's Oncology Group. Cancer. 2007;110:1542-1550.
Wang CH, Hsu TR, Wong TT, Chang KP. Efficacy of temozolomide for recurrent embryonal brain tumors in children. Childs Nerv Syst. 2009;25:535-541.
Baruchel S, Diezi M, Hargrave D, et al. Safety and pharmacokinetics of temozolomide using a dose-escalation, metronomic schedule in recurrent paediatric brain tumours. Eur J Cancer. 2006;42:2335-2342.
Cefalo G, Massimino M, Ruggiero A, et al. Temozolomide is an active agent in children with recurrent medulloblastoma/primitive neuroectodermal tumor: an Italian multi-institutional phase II trial. Neuro Oncol. 2014;16:748-753.
Pourquier P, Waltman JL, Urasaki Y, et al. Topoisomerase I-mediated cytotoxicity of N-methyl-N'-nitro-N-nitrosoguanidine: trapping of topoisomerase I by the O6-methylguanine. Cancer Res. 2001;61:53-58.
Houghton PJ, Stewart CF, Cheshire PJ, et al. Antitumor activity of temozolomide combined with irinotecan is partly independent of O6-methylguanine-DNA methyltransferase and mismatch repair phenotypes in xenograft models. Clin Cancer Res. 2000;6:4110-4118.
Okamoto R, Takano H, Okamura T, et al. O(6)-methylguanine-DNA methyltransferase (MGMT) as a determinant of resistance to camptothecin derivatives. Jpn J Cancer Res. 2002;93:93-102.
Houghton PJ, Cheshire PJ, Hallman JC, et al. Therapeutic efficacy of the topoisomerase I inhibitor 7-ethyl-10-(4-[1-piperidino]-1-piperidino)-carbonyloxycamptothecin against human tumor xenografts: lack of cross-resistance in vivo in tumors with acquired resistance to the topoisomerase I inhibitor 9- dimethylaminomethyl-10-hydroxycamptothecin. Cancer Res. 1993;53:2823-2829.
Grill J, Geoerger B, Gesner L, et al. Phase II study of irinotecan in combination with temozolomide (TEMIRI) in children with recurrent or refractory medulloblastoma: a joint ITCC and SIOPE-Brain tumor study. Neuro Oncol. 2013;15:1236-1243.
Hargrave D, Geoerger B, Frappaz D, et al. A phase II single-arm study of irinotecan in combination with temozolomide (TEMIRI) in children with newly diagnosed high grade glioma: a joint ITCC and SIOPE-Brain tumor study. J Neurooncol. 2013;113:127-134.
Kushner BH, Kramer K, Modak S, et al. Irinotecan plus temozolomide for relapsed or refractory neuroblastoma. J Clin Oncol. 2006;24:5271-5276.
Bagatell R, London WB, Wagner LM, et al. Phase II study of irinotecan and temozolomide in children with relapsed or refractory neuroblastoma: a Children's Oncology Group study. J Clin Oncol. 2011;29:208-213.
Wagner LM, McAllister N, Goldsby RE, et al. Temozolomide and intravenous irinotecan for treatment of advanced Ewing sarcoma. Pediatr Blood Cancer. 2007;48:132-139.
Casey DA, Wexler LH, Merchant MS, et al. Irinotecan and temozolomide for Ewing sarcoma: the Memorial Sloan-Kettering experience. Pediatr Blood Cancer. 2009;53:1029-1034.
Rubie H, Geoerger B, Frappaz D, et al. Phase I study of topotecan in combination with temozolomide (TOTEM) in relapsed or refractory paediatric solid tumours. Eur J Cancer. 2010;46:2763-2770.
Di Giannatale A, Dias-Gasteller N, Devos A, et al. 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. Eur J Cancer. 2014;50:170-177.
Louis DN, Ohgaki H, Wiestler OD, et al. The 2007 WHO classification of tumours of the central nervous system. Acta Neuropathol. 2007;114:97-109.
Louis DN, Perry A, Reifenberger G, et al. The 2016 World Health Organization Classification of tumors of the central nervous system: a summary. Acta Neuropathol. 2016;131:803-820.
Miller AB, Hoogstraten B, Staquet M, Winkler A. Reporting results of cancer treatment. Cancer. 1981;47:207-214.
Zohar S, Teramukai S, Zhou Y. Bayesian design and conduct of phase II single-arm clinical trials with binary outcomes. A tutorial. Contemp Clin Trials. 2008;29:608-616.
Tan SB, Machin D, Tai BC, et al. A Bayesian re-assessment of two phase II trials of gemcitabine in metastatic nasopharyngeal cancer. Br J Cancer. 2002;86:843-850.
Newcombe TG, Altman DG. Proportions and their differences. In: Altman DG, Machin D, Bryant TN, Gardner MJ, eds. Statistics and Confidence. 2nd. London: British Medical Journal Books; 2000:45-56.
Defachelles AS, Bogart E, Casanova M, et al. Randomized phase 2 trial of the combination of vincristine and irinotecan with or without temozolomide, in children and adults with refractory or relapsed rhabdomyosarcoma (RMS). J Clin Oncol. 2019;37. suppl; abstr 10000.
Stevens MF, Hickman JA, Langdon SP, et al. Antitumor activity and pharmacokinetics in mice of 8-carbamoyl-3-methyl-imidazo[5.I-d]-l.2.3.5-tetrazin-4(3H)-one (CCRG 81045;M&B39831). A novel drug with potential as an alternative to dacarbazine. Cancer Res. 1987;47:5846-5852.
Bautista F, Fioravantti V, de Rojas T, et al. Medulloblastoma in children and adolescents: a systematic review of contemporary phase I and II clinical trials and biology update. Cancer Med. 2017;6:2606-2624.
Egan G, Cervone KA, Philips PC, et al. Phase I study of temozolomide in combination with thiotepa and carboplatin with autologous hematopoietic cell rescue in patients with malignant brain tumors with minimal residual disease. Bone Marrow Transplant. 2016;51:542-545.
Mitchell D, Bergendahl G, Ferguson W, et al. A phase 1 trial of TPI 287 as a single agent and in combination with temozolomide in patients with refractory or recurrent neuroblastoma or medulloblastoma. Pediatr Blood Cancer. 2016;63:39-46.