Metronomic Maintenance With Weekly Vinblastine After Induction With Bevacizumab-Irinotecan in Children With Low-grade Glioma Prevents Early Relapse

Abstract

Background: Pediatric low-grade glioma (pLGG) represents the most common brain tumor in childhood. Previous studies have reported that a therapeutic strategy on the basis of the association of bevacizumab alone (B) or in combination with irinotecan (BI) could produce rapid tumor response and clinical improvement in children with pLGG. Nevertheless, a majority of patients relapses shortly (median, 5 mo) after stopping B or BI treatment. We proposed metronomic maintenance with weekly vinblastine added after a 6 months induction of B/BI to prevent early relapse. Patients and Methods: Monocentric retrospective analysis of a patient with pLGG treated with B or BI for 6 months followed by a 12-month maintenance with weekly vinblastine (6 mg/m²) from October 2012 to September 2019 in a single institution. Results: In total, 18 patients (7 males and 11 females) were identified. Because of progression during the B or BI induction 2/18 children were excluded. In total, 16 patients were analyzed with a median age of 10 years (range, 4 to 16 y). A total of 13 patients received BI and 3 patients received B alone. The mean duration of induction was 6.2 months (range, 2 to 12 mo). After induction 5/16 patients had a partial radiologic response, 11/16 patients had stable disease. All patients started maintenance (median duration, 12 mo; range, 3 to 12 mo). With a median follow-up of 3.9 years after the end of B or BI (range, 11 mo to 7.2 y), 15/16 patients were alive and 9/16 patients were progression-free. Seven of 16 children progressed with a median time to progression of 23 months (ranges, 5 to 39 mo). Three of 16 (18%) children progressed during vinblastine maintenance and 4/16 (25%) patients after the end of maintenance. After the total duration of treatment, clinical improvement was noted in 4 patients, 9 patients had stable symptoms, and only 3 patients progressed. One and 2-year event-free survival were, respectively, 81.2% and 56.2%. Two-year overall survival was 93.7%. Conclusions: We report here, the potential benefit and the improvement of progression-free survival by adding metronomic maintenance with weekly vinblastine after initial induction with B or BI in children with low-grade glioma.

Cyclic Metronomic Chemotherapy for Pediatric Tumors: Six Case Reports and a Review of the Literature

“…For example, for adult tumors, a phase III clinical trial of metastatic colorectal cancer with maintenance metronomic capecitabine plus bevacizumab was reported, as were results of a phase III trial in early-stage breast cancer treated with bevacizumab plus metronomic cyclophosphamide and capecitabine [ 7 , 8 ]. For pediatric tumors, a number of phase II clinical trials have reported promising antitumor activity of metronomic chemotherapy, and these studies include those of Kieran and colleagues [ 9 , 10 ], of Andre and colleagues [ 11 , 12 , 13 , 14 , 15 , 16 , 17 ], and of the Baruchel group [ 18 ]. For both adult patients and pediatric tumors, the low toxicity that is frequently observed with this treatment strategy coupled with its (often) relatively low costs [ 4 ] make it an attractive treatment option.…”

Phase I Study of a Combination of Fluvastatin and Celecoxib in Children with Relapsing/Refractory Low-Grade or High-Grade Glioma (FLUVABREX)

“…Roux et al treated 16 patients with B + I, followed by metronomic maintenance with weekly vinblastine. After a median follow-up of 3.9 years after B + I cessation, nine of the sixteen patients were progression-free [ 39 , 40 ]. Because of the SD observed in our LGG patients, we think that the association of celecoxib and fluvastatin may represent an interesting maintenance approach for a patient treated with bevacizumab as those patients rapidly progressed after stopping treatment [ 37 , 38 ].…”

Optic Pathway Glioma in Children with Neurofibromatosis Type 1: A Multidisciplinary Entity, Posing Dilemmas in Diagnosis and Management Multidisciplinary Management of Optic Pathway Glioma in Children with Neurofibromatosis Type 1

“…Bevacizumab is an anti-vascular endothelial growth factor (VEGF) monoclonal antibody, which reduces neovascularization as well as tumor growth by targeting VEGF. It has been previously used in other childhood malignancies and demonstrated good tolerability ( 54 , 55 ). Current applications in patients with NF1 and OPG are refractory patients until further studies elucidate its comprehensive effect on clinical outcomes ( 52 ).…”