Bevacizumab-containing regimen in relapsed/progressed brain tumors: a single-institution experience

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.

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

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

Spini

Ciccone

Rosellini³

et al. 2022

“…Interestingly, this first patient demonstrated a minor response even to bevacizumab monotherapy lasting for 17 months, as demonstrated by MRI. While single case reports, small case series, and early phase trials hinted at an effect of bevacizumab in MB [ 63 , 64 , 65 ], its role in the treatment of recurrent MB was only recently confirmed in a randomized study. The COG phase II screening study randomly assigned patients with relapsed/refractory MB to receive TMZ and irinotecan with or without bevacizumab [ 66 ].…”

Section: Discussionmentioning

confidence: 99%

Improved Long-Term Survival of Patients with Recurrent Medulloblastoma Treated with a “MEMMAT-like” Metronomic Antiangiogenic Approach

Slavc

Mayr

Stepien

et al. 2022

Medulloblastoma (MB) recurrence is usually incurable despite intensive therapy including high-dose chemotherapy. An evolving alternative approach to conventional chemotherapy aims at interfering with tumor angiogenesis at different levels. We report on a novel combinatorial metronomic antiangiogenic approach. The study is a retrospective observational study of 29 consecutive patients with first or multiple recurrences prospectively treated according to the MEMMAT strategy (“MEMMAT-like”) before the formal protocol (MEMMAT; ClinicalTrials.gov Identifier: NCT01356290) started. The study period was 11/2006 to 06/2016. Treatment consisted of daily oral thalidomide, fenofibrate, celecoxib, and alternating 21-day cycles of low-dose oral etoposide and cyclophosphamide supplemented by IV bevacizumab and intraventricular therapy consisting of alternating etoposide and liposomal cytarabine. Median overall survival (OS) after recurrence for the whole group was 29.5 months, OS was 48.3 ± 9.3% at three years and 34.5 ± 8.8% at five years, and progression-free survival was 42.0 ± 9.5% at three years and 29.4 ± 9% at five years. As of 07/2022, 9/29 patients are alive 86 to 164 months after the recurrence that prompted the “MEMMAT-like” therapy. Treatment was primarily out-patient and generally well-tolerated. Toxicities did occur but were manageable. In conclusion, antiangiogenic therapy according to the MEMMAT strategy increased median OS of patients with recurrent MB and may lead to long-term survival. Adherence to the protocol, including intraventricular therapy, appears important.

“…Several case series have reported the use of temozolomide, irinotecan and bevacizumab for rMB [ 142 , 143 , 144 , 145 ]. Most recently, this regimen was one arm of the randomised phase II COG study, ACNS0821 (NCT01217437) designed to compare temozolomide and irinotecan with/without bevacizumab.…”

Section: Treatment Modalities and Considerationsmentioning

confidence: 99%

Relapsed Medulloblastoma in Pre-Irradiated Patients: Current Practice for Diagnostics and Treatment

Hill

Plasschaert

Timmermann

et al. 2021

Relapsed medulloblastoma (rMB) accounts for a considerable, and disproportionate amount of childhood cancer deaths. Recent advances have gone someway to characterising disease biology at relapse including second malignancies that often cannot be distinguished from relapse on imaging alone. Furthermore, there are now multiple international early-phase trials exploring drug–target matches across a range of high-risk/relapsed paediatric tumours. Despite these advances, treatment at relapse in pre-irradiated patients is typically non-curative and focuses on providing life-prolonging and symptom-modifying care that is tailored to the needs and wishes of the individual and their family. Here, we describe the current understanding of prognostic factors at disease relapse such as principal molecular group, adverse molecular biology, and timing of relapse. We provide an overview of the clinical diagnostic process including signs and symptoms, staging investigations, and molecular pathology, followed by a summary of treatment modalities and considerations. Finally, we summarise future directions to progress understanding of treatment resistance and the biological mechanisms underpinning early therapy-refractory and relapsed disease. These initiatives include development of comprehensive and collaborative molecular profiling approaches at relapse, liquid biopsies such as cerebrospinal fluid (CSF) as a biomarker of minimal residual disease (MRD), modelling strategies, and the use of primary tumour material for real-time drug screening approaches.