A phase I/II study of bevacizumab, irinotecan and erlotinib in children with progressive diffuse intrinsic pontine glioma
| Autor: | Fatma E El-Khouly, Sophie E. M. Veldhuijzen van Zanten, Esther Sanchez Aliaga, W. Peter Vandertop, Dannis G. van Vuurden, N. Harry Hendrikse, Dewi P. Bakker, Gertjan J.L. Kaspers, Marc H. A. Jansen |
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| Přispěvatelé: | Pediatric surgery, ACS - Diabetes & metabolism, Amsterdam Neuroscience - Neuroinfection & -inflammation, Radiology and nuclear medicine, CCA - Cancer Treatment and quality of life, Clinical pharmacology and pharmacy, Amsterdam Neuroscience - Neurovascular Disorders, Neurosurgery, Radiology & Nuclear Medicine, ANS - Neurovascular Disorders, ANS - Systems & Network Neuroscience, CCA - Cancer Treatment and Quality of Life |
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Oncology
Cancer Research medicine.medical_specialty Bevacizumab medicine.medical_treatment Astrocytoma Irinotecan Targeted therapy Erlotinib Hydrochloride Diffuse intrinsic pontine glioma (DIPG) SDG 3 - Good Health and Well-being Internal medicine Antineoplastic Combined Chemotherapy Protocols medicine Brain Stem Neoplasms Humans Progression-free survival Child EGFR inhibitors business.industry Diffuse Intrinsic Pontine Glioma Radiation therapy Erlotinib Neurology Tolerability Cohort Disease Progression Quality of Life Clinical Study Neurology (clinical) business medicine.drug |
| Zdroj: | Journal of Neuro-Oncology, 153(2), 263-271. Kluwer Academic Publishers Journal of Neuro-Oncology, 153(2), 263-271. Kluwer Academic Journal of neuro-oncology, 153(2), 263-271. Kluwer Academic Publishers Journal of Neuro-Oncology El-Khouly, F E, Veldhuijzen van Zanten, S E M, Jansen, M H A, Bakker, D P, Sanchez Aliaga, E, Hendrikse, N H, Vandertop, W P, van Vuurden, D G & Kaspers, G J L 2021, ' A phase I/II study of bevacizumab, irinotecan and erlotinib in children with progressive diffuse intrinsic pontine glioma ', Journal of Neuro-Oncology, vol. 153, no. 2, pp. 263-271 . https://doi.org/10.1007/s11060-021-03763-1 |
| ISSN: | 0167-594X |
| DOI: | 10.1007/s11060-021-03763-1 |
| Popis: | Introduction This study investigates the safety, tolerability, and preliminary efficacy of combined treatment with VEGF inhibitor bevacizumab, topoisomerase I inhibitor irinotecan, and EGFR inhibitor erlotinib in children with progressive diffuse intrinsic pontine glioma (DIPG). Methods Biweekly bevacizumab (10 mg/kg) and irinotecan (125 mg/m2) were combined with daily erlotinib. Two cohorts received increasing doses of erlotinib (65 and 85 mg/m2) following a 3 + 3 dose-escalation schedule, until disease progression with a maximum of one year. Dose-limiting toxicities (DLT) were monitored biweekly. Secondary progression free survival (sPFS) and overall survival (OS) were determined based on clinical and radiological response measurements. Quality of life (QoL) during treatment was also assessed. Results Between November 2011 and March 2018, nine patients with disease progression after initial radiotherapy were enrolled. Median PFS at start of the study was 7.3 months (range 3.5–10.0). In the first dose cohort, one patient experienced a DLT (grade III acute diarrhea), resulting in enrollment of three additional patients in this cohort. No additional DLTs were observed in consecutive patients receiving up to a maximum dose of 85 mg/m2. Median sPFS was 3.2 months (range 1.0–10.9), and median OS was 13.8 months (range 9.3–33.0). Overall QoL was stable during treatment. Conclusions Daily erlotinib is safe and well tolerated in doses up to 85 mg/m2 when combined with biweekly bevacizumab and irinotecan in children with progressive DIPG. Median OS of the study patients was longer than known form literature. |
| Databáze: | OpenAIRE |
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