Intratumoral tocilizumab in children with cystic craniopharyngiomas: a pilot targeted therapy trial

Purpose : The craniopharyngioma, although benign, exhibits aggressive behavior due to its capacity to invade the surrounding neurovascular structures. The conventional treatment with surgery and radiotherapy is related to significant morbidity and impact on quality of life. Recent findings prove the increase of interleukin-6 (IL-6) and its receptor (IL-6R) in those tumors, making tocilizumab, an anti-IL-6R antibody used for rheumatological diseases, a possible targeted therapy. The present study investigated the safety and effectiveness of the intracystic application of tocilizumab in children with cystic craniopharyngiomas. Methods : longitudinal prospective analysis of the use of the maximum dose of 3,6 mg/kg of intracystic tocilizumab in seven individuals under 20 years old who have a confirmed diagnosis of cystic adamantinomatous craniopharyngioma. The treatment took two years. Tumor volume, IL-6 quantification, tumor fluid color, endocrinological and visual dysfunctions, and patient/main care quality of life before and after treatment were evaluated. Results : out of nine treated cysts in seven patients, only three of them (33,3%) showed tumor control during the monitoring period. Six patients (85,7%) needed to have their dose trebled due to progression. There was no systemic or local toxicity. The color of the tumor fluid was correlated to the levels of IL-6 (p = 0.05), but not to the clinical outcome. There were no significant changes in the levels of life quality or visual/endocrine functionality. The cranium Computer Tomography (CT) and the brain Magnetic Resonance (MR) showed a strong correlation to the evaluation of the tumor volume (p < 0,01). Conclusion : The use of intratumoral tocilizumab was shown to be safe; however, not effective at the frequency and dosage used. The tumor fluid color and IL-6 levels might be related to the prognosis in larger series. Further studies should explore higher doses and frequency when applying it in order to reach a therapeutic optimization.