Introduction: Patients with refractory or recurrent CNS embryonal or germ cell tumors have poor prognosis and survivors suffer neuropsychological sequalae from radiotherapy and ototoxicity from chemotherapy. Prior retrospective studies suggest intra-arterial (IA) chemotherapy in conjunction with blood-brain barrier disruption (BBBD) may improve outcomes in patients with these challenging tumors.
Methods: In this prospective study, patients aged 1 to 30 with recurrent or refractory CNS embryonal or germ cell tumors were treated on 2 consecutive days, every 4 weeks, for up to a year with dose intensive IA carboplatin and IA melphalan with BBBD. The study objectives are to: determine the maximum tolerated dose of IA melphalan, estimate response rate, describe 2-year progression-free and overall survival, describe audiology and neuropsychological outcomes and describe overall toxicity.
Results: Nine patients were enrolled in the study (6 male) with a mean age was 14.75 years. There were three patients with medulloblastoma, two with atypical teratoid rhabdoid tumor, two with germ cell tumors, one with metastatic testicular teratoma, and one with PNET. The majority of patients thus far were treated at a melphalan dose of 6 mg/m2 for two days. Of the study participants two had stable disease, three had partial response, and three had disease progression. There were a total of 16 adverse events of grades three and higher with the majority being grade 3(63%). The most common adverse event was electrolyte disorder in 38% of patients, and bone marrow suppression in 25% of patients.
Conclusions: This therapy is well tolerated and appears safe. The current melphalan dose is 6 mg/m2. Toxicity is predominantly related to electrolyte disturbances and bone marrow suppression. There appears to be a subgroup that responds to this therapy but further investigation is needed. The trial continues with further enrollment.
Patient Care: This therapy is safe, and can potentially improve progression-free and overall survival in patients with these challenging tumors.
Learning Objectives: By the conclusion of this session, participants will understand: (1) the rationale for use of intra-arterial chemotherapy delivery in conjunction with blood brain barrier for embryonal or germ cell CNS tumors, and (2) the preliminary safety and efficacy of this therapy in pediatric patients