Safety of Anti-Angiogenic Drugs in Pediatric Patients with Solid Tumors: A Systematic Review and Meta-Analysis

Abstract

Cancer is a clinical condition that can benefit from anti-angiogenic drugs (AADs). Given the low prevalence and the heterogeneity of childhood cancers, information about the safety of these drugs in pediatric patients is partially assessed. The aim of this study was to evaluate the safety of AADs in pediatric patients with solid tumors. Clinical trials and observational studies were searched in PubMed, ISI Web of Science, and ClinicalTrials database For each included study, adverse events (AEs) were extracted. A meta-analysis was conducted by pooling proportions of AEs using a random intercept logistic regression model. Seventy studies were retrieved. Most part were clinical trials (55 out of 70), and only fifteen observational studies were found. Overall, proportion of serious and non-serious AEs of AADs used as monotherapy was 46% and 89%, respectively. Proportions of serious AEs varied among drugs: sunitinib, 79%; lenvatinib, 64%; sorafenib, 48%; ramucirumab, 41%; pazopanib, 30%; and vandetanib, 27%. A higher proportion of non-serious hematological AEs was found in the patients receiving pazopanib with respect to sunitinib and lenvatinib. The safety profile of AADs has been extensively investigated for mostly drugs in phase I and II trials and is limited to acute toxicities. Overall, one out of two patients using AAD drugs in monotherapy experienced a serious AE despite proportions varied per single drugs. When AADs were combined with standard chemotherapy, the proportion of AEs varied in relation to the single combinations.

Uncovering Knowledge Gaps in the Safety Profile of Antiangiogenic Drugs in Cancer Patients: Insights from Spontaneous Reporting Systems Studies

“…Interestingly, in agreement with a meta-analysis on the safety of AADs in the pediatric population, lenvatinib was associated with the most powerful signal of hypothyroidism reports [ 6 , 18 ]. Some further considerations could also be made: the different signals that arose from the pharmacovigilance studies may be due to the database used, the comparator group, the disproportionality methodology applied (Reporting Odds Ratio or Proportional Reporting Ratio), and the confounding factors evaluated.…”

“…The multi-inhibition strategy was developed to avoid resistance to anti-VEGF drugs and improve efficacy [ 3 ]. They have become an important part of some tumors’ treatment, both in monotherapy or in combination [ 4 , 5 , 6 ].…”

“…The use of AADs in special populations requires careful consideration of the individual patient’s characteristics and the potential risks and benefits of treatment. Close monitoring and management of side effects may be necessary to ensure safe and effective treatment [ 6 ]. Despite the challenges, AADs have shown promise in the treatment of cancer and continue to be an active area of research [ 8 , 9 , 10 ].…”

Real-life experience with a “modified-MEMMAT” regimen for relapsed medulloblastoma

“…Several studies have explored various MC combinations, initially for palliative treatment and later extended to high-risk solid tumors in children who completed standard chemo and radiotherapy [24].…”

Efficacy of Off-Label Use of Anticancer Drugs in Oncology

“…[24]. Несколько ис следований показали эффективность и безопасность указанного агента при рецидивирующей медуллобла стоме и глиоме у детей [25][26][27][28][29][30][31][32], что, вероятно, объяс няет высокую распространенность его использования «вне инструкции» у этой категории пациентов с ЗНО центральной нервной системы (ЦНС) [24]. A. M. Schmitt и соавторы, изучая характеристики и вы живаемость пациентов с доступом и без доступа к за планированному назначению противоопухолевых агентов «вне инструкции» в трех крупных онкологи ческих центрах Швейцарии (с января 2015 по июль 2018 г.…”