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Rare Disease: Vinblastine Controls Neurofibromatosis-1 with Optic Glioma

Susman, Ed

doi: 10.1097/01.COT.0000471986.11116.76
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CHICAGO—Young patients diagnosed with neurofibromatosis and low-grade optic-pathway glioma appear to respond to treatment with vinblastine, researchers reported here at the American Society of Clinical Oncology Annual Meeting (Abstract 2019).

“We think that weekly vinblastine is well tolerated and can be used in children with neurofibromatosis type-1 [NF-1] with optic pathway glioma as first-line chemotherapy with good results,” Alvaro Lassaletta, MD, a clinical fellow in neuro-oncology at the Hospital for Sick Children in Toronto, said in an interview at his poster study.

He and his colleagues identified 54 children who were diagnosed with neurofibromatosis. Of that group, 13 had the hereditary form of the disease known as NF-1, all of whom had optic pathway gliomas. “This is a very rare disease,” he said. “In two years we identified just 13 children with NF-1 across Canada.

“We found that children with NF-1 have a greater overall risk of optic pathway glioma, but they also appear to respond better to treatment than the children with non-NF-1 tumors did,” Lassaletta said, noting that about 15 percent of children diagnosed with NF-1 will develop a brain tumor.

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Less Aggressive Therapy

Of the 13 children treated with vinblastine—a less aggressive treatment than the standard of vincristine plus carboplatin, two had a partial response; one had a minor response, and eight had stable disease. Two of the children had disease progression during the median follow-up of 5.37 years. The median age of the NF-1 children was 3.84 years at the start of the trial, and the non-NF-1 patients had a median age of seven.

The median progression-free survival rate was 85 percent. When compared with the children who were diagnosed with sporadic neurofibromatosis, the children with NF-1 did better. A total of 42 percent of the 41 patients with non-NF-1 disease achieved progression-free survival, a difference that reached statistical significance.

When specifically looking at non-NF-1 patients with optic pathway glioma, 42 percent achieved five-year progression-free survival. There have been no deaths among these children; three of the non-NF-1 patients died of disease progression.

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Asked for his perspective, Mark Atlas, MD, Director of the Brain Tumor Program at Cohen Children's Medical Center in New Hyde Park, New York, said: “The standard therapy for patients with NF-1 and low-grade glioma is vincristine and carboplatin, and the data from [a Children's Oncology Group] study demonstrates a five-year event-free survival of 67.8 percent. Here the Canadian group shows an 85 percent progression-free survival.

“Event-free survival and progression-free survival are close, but not 100 percent comparable, although these results are unlikely to be statistically significantly different. “The majority of patients had stable disease, while in our unpublished experience, a greater percentage of patients with NF-1 have a good partial response using vincristine and carboplatin.”

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‘Second Useful Regimen’

Atlas said the study provides a second useful regimen for the treatment of NF-1 patients with optic glioma and low-grade glioma. “To determine if one is superior, a randomized study of the two regimens would need to be done, but this is unlikely to be a priority. I think one could use either regimen upfront, though I would likely reserve vinblastine for patients who progress on the vincristine-plus-carboplatin or for those children with allergy to carboplatin.”

Lassaletta said: “To date, the first-line chemotherapy treatment in the majority of countries for children with NF-1 and optic pathway glioma is vincristine plus carboplatin. The toxicity of this regimen consists mostly of neuropathy, allergic reactions, and hearing loss.”

He said that because vinblastine had shown promising activity in a Phase II study in children with recurrent or refractory low-grade glioma, the team decided to test whether vinblastine could be used in the setting of low-grade glioma: “Low-grade glioma is not a rapidly fatal disease, but when it affects the optic pathway, it can lead to blindness.”

The study enrolled patients under age 18 who were diagnosed with unresectable or progressive low-grade glioma if they had not received previous treatment with chemotherapy or radiation. Vinblastine was administered weekly at a dose of 6 mg/m2 over a period of 70 weeks. Treatment was discontinued for patients who had disease progression on two consecutive imaging studies or evidence of clinical progression.

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Less Toxicity

Lassaletta said that in addition to longer progression-free survival, the difference in treatments gave the children on vinblastine a better toxicity profile, which translated to a better overall quality of life—and the treatment was well tolerated.

“All patients completed the 70 weeks of vinblastine,” he said. “However, five of the 13 patients with NF-1 required dose reductions.”

The most common toxicity was hematological. One patient with NF-1 disease had grade 3 toxicity, although 10 patients with non-NF-1 did have Grade 3 neutropenia. The NF-1 children had two bouts of febrile neutropenia. None of the NF-1 patients required red blood cells infusion.

He said there were no toxic deaths in the study, and none of the NF-1 children needed radiation to control their disease; but six of the non-NF-1 patients have undergone radiation.

Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
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