Carboplatin and vincristine chemotherapy for children with newly diagnosed progressive low-grade gliomas

Abstract

The optimum treatment of nonresectable low-grade gliomas of childhood remains undecided. There has been increased interest in the use of chemotherapy for young children, but little information concerning the long-term efficacy of such treatment. Seventy-eight children with a mean age of 3 years (range 3 months-16 years) who had newly diagnosed, progressive low-grade gliomas were treated with combined carboplatin and vincristine chemotherapy. The patients were followed for a median of 30 months from diagnosis, with 31 patients followed for more than 3 years. Fifty-eight children had diencephalic tumors, 12 had brainstem gliomas, and three had diffuse leptomeningeal gliomas. Forty-four (56%) of 78 patients showed an objective response to treatment. Progression-free survival rates were 75 ± 6% at 2 years and 68 ± 7% at 3 years. There was no statistical difference in progression-free survival rates between children with neurofibromatosis Type 1 and those without the disease (2-year, progression-free survival 79 ± 11% vs. 75 ± 6%, respectively). The histological subtype of the tumor, its location, and its maximum response to chemotherapy did not have an impact on the duration of disease control. The only significant prognostic factor was age: children 5 years old or younger at the time of treatment had a 3-year progression-free survival rate of 74 ± 7% compared with a rate of 39 ± 21% in older children (p < 0.01). Treatment with carboplatin and vincristine is effective, especially in younger children, in controlling newly diagnosed progressive low-grade gliomas.Key Words * glioma * chiasmatic glioma * low-grade glioma * brainstem tumor * chemotherapy * children Gliomas comprise more than 50% of all childhood brain tumors and approximately 80% of these lesions

Long term follow up of 69 patients treated for optic pathway tumours before the chemotherapy era

“…When the impact of chemotherapy or radiotherapy on optic pathway glioma is analysed in further trials, it should be borne in mind that radiological responses might be delayed and that children with stable disease at the end of radiotherapy might be cured, as was the case for almost half of our patients. In comparison, the best response rate with chemotherapy in newly diagnosed young patients reaches 57% of significant radiological responses with carboplatin and vincristine 14. The relapse rate is low in patients treated with radiotherapy,24 as confirmed in this large series.…”

Phase II study of carboplatin (CBDCA) in progressive low-grade gliomas

“…The toxicity of the therapy is minimal, and, of note, the CR and PR response rate in our study is identical to that achieved with the regimen of carboplatin and vincristine used by Packer, et al [7] Furthermore, patients harboring OPTs or JPAs had an even higher response rate of 42% compared with no response in the other six patients harboring other types of LGGs in different sites of the brain. Although few conclusions can be drawn based on the results in those six patients, there were nevertheless four patients with SD after 12 cycles of carboplatin.…”

“…[6] There have been previous reports in which the efficacy of chemotherapy to treat progressive LGGs in the pediatric population has been detailed. These chemotherapy regimens have included actinomycin and vincristine, [8] carboplatin, [3,5] carboplatin and vincristine, [7] and a five-drug treatment incorporating procarbazine, 6-thioguanine, dibromodulcitol, lomustine, and vincristine. [10] The largest study to date, in which carboplatin and vincristine were administered to children with newly diagnosed progressive LGGs, was recently updated by Packer, et al [7] This regimen produced a progression-free survival rate of 75 ± 6% at 2 years and 68 ± 7% at 3 years in 78 children, who ranged in age between 3 months and 16 years.…”

“…A diverse spectrum of agents have been used in the treatment of LGGs in the pediatric population, including vincristine, actinomycin D, etoposide, carboplatin, carmustine, and combinations of these regimens, particularly carboplatin and vincristine. [3,5,[7][8][9][10] We previously reported a single institution experience in which carboplatin was used to treat children with progressive optic pathway glioma. [5] The success of this approach, coupled with its modest toxicity as a single agent, has led us to use carboplatin to treat both children and adults harboring progressive LGGs.…”

Epidermal growth factor receptorgene amplification and expression in disseminated pediatric low-grade gliomas

“…Epidermal growth factor receptor is an important target for further research because of the small molecules that inhibit this receptor. 20,28 In the context of disseminated pediatric LGGs, it will probably be better to add these agents as adjuncts to the standard chemotherapy protocols, because current protocols are successful in disease control 19 and because only subsets of the cells express EGFR.…”