ArticlePediatric blood & cancer2013
Phase I trial and pharmacokinetic study of sorafenib in children with neurofibromatosis type I and plexiform neurofibromas.
Article in Pediatric blood & cancer, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03231306 (A Phase II Study of Binimetinib in Children and Adults With NF1 Associated Plexiform Neurofibromas), which is not on this map. Cited by 46 papers, 2 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
A Phase II Study of Binimetinib in Children and Adults With NF1 Associated Plexiform Neurofibromas (PNOC010)
Who cites it
46 citing papers in PubMed, 2 syntheses or guidelines pooled it, 75 citations in OpenAlex.
- Patient-reported outcomes of pain and physical functioning in neurofibromatosis clinical trials.Neurology · 2016Guideline
- Sleep and pulmonary outcomes for clinical trials of airway plexiform neurofibromas in NF1.Neurology · 2016Guideline
- Phase II study of sorafenib in children with recurrent or progressive low-grade astrocytomas.Neuro-oncology · 2014Trial
- Trial
- Review
- Biomarker Landscape in RASopathies.International journal of molecular sciences · 2024Review
- Past, Present, and Future Therapeutic Strategies for NF-1-Associated Tumors.Current oncology reports · 2024Review
- Schwann cell derived pleiotrophin stimulates fibroblast for proliferation and excessive collagen deposition in plexiform neurofibroma.Cancer gene therapy · 2024Article
- Article
- Management of neurofibromatosis type 1-associated plexiform neurofibromas.Neuro-oncology · 2022Review
- Pharmacokinetically guided dosing of oral sorafenib in pediatric hepatocellular carcinoma: A simulation study.Clinical and translational science · 2021Article
- Status and Recommendations for Incorporating Biomarkers for Cutaneous Neurofibromas Into Clinical Research.Neurology · 2021Article
- Pharmacological Approaches in Neurofibromatosis Type 1-Associated Nervous System Tumors.Cancers · 2021Review
- Rationale for the use of tyrosine kinase inhibitors in the treatment of paediatric desmoid-type fibromatosis.British journal of cancer · 2021Review
- Spontaneous and Engineered Large Animal Models of Neurofibromatosis Type 1.International journal of molecular sciences · 2021Review
- Current status of MEK inhibitors in the treatment of plexiform neurofibromas.Child's nervous system : ChNS : official journal of the International Society for Pediatric Neurosurgery · 2020Review
- Treatment of malignant peripheral nerve sheath tumors in pediatric NF1 disease.Child's nervous system : ChNS : official journal of the International Society for Pediatric Neurosurgery · 2020Review
- Combination therapy with sorafenib and celecoxib for pediatric patients with desmoid tumor.Pediatric hematology and oncology · 2020Article
- Management of cutaneous neurofibroma: current therapy and future directions.Neuro-oncology advances · 2020Review
- Clinical trial design in neurofibromatosis type 1 as a model for other tumor predisposition syndromes.Neuro-oncology advances · 2020Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
14 authors at 4 institutions in 1 country.
Funding
Abstract
backgroundSorafenib targets multiple pathways thought to be crucial in growth of plexiform neurofibroma (PN) in children with neurofibromatosis type 1 (NF1). Sorafenib has been tolerated with manageable toxicities in adults and children with refractory cancer. We conducted a separate study in this population. Monitoring long-term toxicities such as effects on growth and obtaining additional pharmacokinetic data were of importance due to the young age and long duration of therapy seen in previous phase I trials in children with NF1. PROCEDURE: Children ≥3 and ≤18-year-old with NF1 and inoperable PN were eligible. Sorafenib was administered orally twice daily for consecutive 28-day cycles. Maximum tolerated dose (MTD) was determined from toxicities observed during the first three cycles.
resultsNine children enrolled, median age 8 (6-12) years. At the starting 115 mg/m(2) /dose (n = 5), two experienced dose-limiting grade 3 pain in their PN. At the de-escalated 80 mg/m(2) /dose (n = 4), approximately 40% of the pediatric solid tumor MTD, two had dose-limiting toxicity (grade 3 rash and grade 4 mood alteration), exceeding the MTD. At 80 mg/m(2) /dose, the median AUC(0-12 hours) at steady-state was 39.5 µg hours/ml. Toxicities appeared to correspond with decreases in quality of life (QOL). No tumor shrinkage was observed.
conclusionsChildren with NF1 and PN did not tolerate sorafenib at doses substantially lower than the MTD in children and adults with malignant solid tumors. Future trials with targeted agents for children with NF1 may require a more conservative starting dose and separate definitions of dose limiting toxicities (DLT) than children with cancer.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.