pyrimidinones and Paronychia

To describe a series of children with extensive PNF or treatment refractory PLGG treated on a compassionate basis with trametinib.. We report on six patients with NF-1 treated with trametinib on a compassionate basis at British Columbia Children's Hospital since 2017. Data were collected retrospectively from the patient record. RAPNO and volumetric criteria were used to evaluate the response of intracranial and extracranial lesions, respectively.. Subjects were 21 months to 14 years old at the time of initiation of trametinib therapy and 3/6 subjects are male. Duration of therapy was 4-28 months at the time of this report. All patients had partial response or were stable on analysis. Two patients with life-threatening PNF had a partial radiographic response in tandem with significant clinical improvement and developmental catch up. One subject discontinued therapy after 6 months due to paronychia and inadequate response. The most common adverse effect (AE) was grade 1-2 paronychia or dermatitis in 5/6 patients. There were no grade 3 or 4 AEs. At the time of this report, five patients remain on therapy.. Trametinib is an effective therapy for advanced PNF and refractory PLGG in patients with NF-1 and is well tolerated in children. Further data and clinical trials are required to assess tolerance, efficacy and durability of response, and length of treatment required in such patients.

Topics: Adolescent; Antineoplastic Agents; Brain Neoplasms; British Columbia; Child; Child, Preschool; Compassionate Use Trials; Dermatitis, Atopic; Drug Resistance, Neoplasm; Female; Glioma; Humans; Infant; Male; Neurofibroma, Plexiform; Neurofibromatosis 1; Paronychia; Pyridones; Pyrimidinones; Retrospective Studies; Treatment Outcome

Paronychia has been described as a side effect in patients undergoing treatment with MEK (mitogen activated protein kinase enzyme) inhibitors. It is usually a recurrent condition that can have a significant impact in the quality of life. Topical beta blocker treatment has been described as an effective therapy in antineoplastic-induced pyogenic granulomas and in antineoplastic-induced paronychia. We describe the first case treated with topical timolol for a trametinib-induced paronychia in a pediatric patient that allowed to continue the third line antineoplastic therapy for his glioma.

Topics: Administration, Topical; Adrenergic beta-Antagonists; Antineoplastic Agents; Child, Preschool; Glioma; Humans; Male; Paronychia; Protein Kinase Inhibitors; Pyridones; Pyrimidinones; Timolol; Treatment Outcome