Phase II study of metronomic chemotherapy with thalidomide, carboplatin-vincristine-fluvastatin in the treatment of brain stem tumors in children

Abstract

Background: Brain stem tumors (BST) constitute 20% of all intracranial tumors. Survival for these patients has been very poor worldwide. Four different treatment schemes have been evaluated at our institution, with only a discrete increment in survival when treated with carboplatin-vincristine and fluvastatin (CVF). Low-dose, continuous antiangiogenic treatment has been recently introduced in the treatment of cancer. Our objective was to determine tumor response to metronomic chemotherapy combined with an antiangiogenic drug and fluvastatin and to calculate the survival of pediatric patients with brain stem tumors.

Methods: This was a phase II study. A magnetic resonance (MRI) study was made at inclusion and after the fourth course. Routine laboratory analyses were performed prior to each treatment scheme. Patients received four courses of chemotherapy every 28 days consisting of thalidomide alternating with fluvastatin every 14 days and combined with carboplatin and vincristine every 14 days followed by radiotherapy (56 cGy) and four more courses of the same chemotherapy. Toxicity was evaluated according to Miller criteria.

Results: Nine recently diagnosed BST patients were included. Five patients had low-grade astrocytomas, three patients had glioblastoma multiforme, and one patient presented high-grade astrocytoma. There was a significant reduction in tumor volume and a significant increase in survival at 24 months. Two patients died. Toxicity included carboplatin allergy in one patient, grades 1 and 3 neutropenia in two patients, and grade 4 thrombocytopenia in two patients.

Conclusions: Metronomic treatment with carboplatin and vincristine associated with fluvastatin and thalidomide significantly increased survival of pediatric brain stem tumor patients. Tumor volume showed a significant reduction. Quality of life was also increased. Sample size must be increased in order to make final conclusions.