Vinblastine monotherapy produced rates of overall and progression-free survival in children with treatment-naive pediatric low-grade glioma (PLGG) similar to that of current therapies and had favorable toxicity and quality-of-life profiles, according to the results of a study published in the Journal of Clinical Oncology.
“Vinblastine is easy to administer and inexpensive, has minimal short-term and long-term toxicity, and demonstrates a relatively maintained quality of life,” wrote researchers led by Alvaro Lassaletta, MD, of the Hospital for Sick Children in Toronto. “Hence, implementation of vinblastine chemotherapy as first-line treatment holds promise for all children and especially for those in middle- or low-income countries where financial restraints and treatment-related toxicities are major challenges.”
Vinblastine monotherapy has shown activity and has a low toxicity profile when used to treat PLGG in children who had failed first-line chemotherapy and/or radiation. With this study, Lassaletta and colleagues tested the use of vinblastine in treatment-naive disease.
The study included 54 patients aged 18 or younger with unresectable or progressive PLGG. The median age of patients was 8 years. Vinblastine was given weekly at 6 mg/m2 for a period of 70 weeks. The researchers assessed vision, quality of life, neurofibromatosis type 1 (NF1) status, and BRAF mutation status.
The overall response rate to vinblastine was 25.9%, and disease stabilization was achieved in 87.0% of patients. Twenty percent of children with optic pathway glioma had a visual improvement with vinblastine treatment.
Patients administered the therapy had a 5-year overall survival rate of 94.4% and a 5-year progression-free survival rate of 53.2%. About 25% of patients in the study had NF1 and these patients were younger at diagnosis compared with those who did not have NF1. Patients with NF1 had significantly better progression-free survival compared with patients without NF1 (85.1% vs 42.0%; P = .012).
Thirty-one tumor samples were analyzed for BRAF V600E mutations and three tested positive (9.7%). One patient with hypothalamic tumor had disease progression while on vinblastine and was taken off study. The other two patients with BRAF-positive disease did not show progression on follow-up.
Adverse events were mild and no patient had to discontinue treatment as a result of toxicity. About one-quarter of patients tolerated the planned dose of vinblastine; 16 patients had a dose reduction to 5 mg/m2 and 17 patients had a reduction to 4 mg/m2. There were no survival differences observed according to treatment dose.
The most frequent adverse events were neutropenia (75.9%), upper respiratory tract infection (52%), and fever (43%). About 40% of patients experienced grade 3 neutropenia and about 35% experienced grade 4 neutropenia.
The researchers also evaluated quality of life in 49 of the 54 patients. There were no significant differences in quality of life from baseline to week 26 of treatment to end of treatment.
“Knowing that children with PLGG may require several lines of chemotherapy and that similar outcomes have been observed between first-line, second-line, and even successive chemotherapy regimens, the use of vinblastine as first-line chemotherapy seems justified as a result of its low toxicity profile,” the researchers wrote.