Single agent vinorelbine in pediatric patients with progressive optic pathway glioma

Abstract

The management of progressive unresectable low-grade glioma remains controversial. Treatment options have included radiotherapy, and more recently chemotherapy, usually following an initial period of observation. Within this context, we evaluated vinorelbine, a semi-synthetic vinca alkaloid that has shown evidence of activity against glioma. From July 2007 an institutional protocol with vinorelbine (30 mg/m(2) days 0, 8, 22) for a total of 18 cycles, has been conducted at IOP/GRAACC/UNIFESP for children with optic pathway glioma (OPG). The main objectives were clinical and radiological response, as well as toxicity profile. Twenty-three patients with progressive OPG with a mean age of 69 months (4-179) were enrolled. Three patients had a diagnosis of neurofibromatosis type 1. Twenty-two patients were assessable for response with an overall objective response rate of 63 %, with eight patients showing stable disease. The most important toxicity was hematologic (grade III/IV neutropenia) observed in four patients. Gastrointestinal toxicity (grade I/II vomiting) was observed in seven patients and only 1 patient showed grade I peripheral neuropathy. The median progression-free survival (PFS) was 33 months (6.9-69) with a 3 and 5 year PFS of 64 ± 19 and 37 ± 20 %, respectively, for an overall 3 and 5 year-survival of 95 ± 10 %. This study suggests that vinorelbine may be an interesting option for pediatric low-grade gliomas, showing low toxicity profile and providing a good quality of life for patients with such chronic disease.

Outcomes Following Proton Therapy for Pediatric Low-Grade Glioma

“…Recently, investigators have suggested that the use of frontline chemotherapy in pediatric low-grade glioma may be associated with inferior visual outcomes and progression-free survival. 21,[29][30][31][32] Our data do not support this finding. Nonetheless, our data suggest that the therapeutic ratio of proton therapy within the first 5 years of treatment compares favorably with contemporary chemotherapy options.…”

“…Nonetheless, our data suggest that the therapeutic ratio of proton therapy within the first 5 years of treatment compares favorably with contemporary chemotherapy options. 29,30 If this result bears out over longer follow-up and proton therapy becomes more widely available, re-examination of the role of chemotherapy (and socalled systemic "targeted agents") within the algorithm of pediatric LGG management may be warranted. Perhaps one day a 5-year-old child with a new diagnosis will need not undergo 3 (or more) cycles of chemotherapy and their associated toxicity before curative radiation, a strategy pursued in 13% of the patients in our series.…”

A European randomised controlled trial of the addition of etoposide to standard vincristine and carboplatin induction as part of an 18-month treatment programme for childhood (≤16 years) low grade glioma – A final report

“…As well, a small series investigated the combination of bevacizumab and irinotecan, vinorelbine or temozolomide [37], [38], [39], [40], [41], [42]. Efficacy was judged by assessing radiological tumour response, while survival (OS) and progression-free survival (PFS) data were not always available.…”

Can metronomic maintenance with weekly vinblastine prevent early relapse/progression after bevacizumab–irinotecan in children with low‐grade glioma?

“…Achieving to maintain sustained stable disease in pediatric patient with LGG, while limiting both acute and long-term toxicities is challenging [2][3][4][5][6][7][8][9][10]. Recently, the combination of bevacizumab and irinotecan has been reported to produce rapid tumor response in some children with recurrent LGG [3][4][5][6], but patients frequently relapse shortly after stopping treatment [4].…”