Preirradiation Ifosfamide, Carboplatin, and Etoposide for the Treatment of Anaplastic Astrocytomas and Glioblastoma Multiforme: A Phase II Study

Abstract

Background Central nervous system (CNS) tumors are the second most common pediatric tumors. Astrocytomas represent 35% of all CNS tumors in children. Traditional treatment of anaplastic astrocytoma (AA) and glioblastoma multiforme (GM) consisting of surgery-radiotherapy-chemotherapy with nitrosoureas has resulted in a survival rate of 26% at 1 year. Neoadjuvant chemotherapy has proven good results in the treatment of other solid tumors. Chemotherapy with ifosfamide, carboplatin, and etoposide (ICE) permits synergism among the different drugs and sensitizes the tumor to radiotherapy. Our objective was to evaluate the efficacy, security, and survival rate of postoperative chemotherapy with ICE in pediatric patients with AA or GM. Methods Phase II study. We evaluated 11 children with AA or GM who had received no prior treatment. A magnetic resonance image (MRI) study of the tumor was made after surgery to evaluate residual tumor and routine laboratory analysis. Chemotherapy with carboplatin, ifosfamide and etoposide was given every 3 weeks for four courses. MRI studies were repeated after the second and last courses and laboratory analyses were carried out before each course to evaluate toxicity. Each patient then received hyperfractionated radiotherapy and a final MRI was done at the end of the treatment. Results Sixty percent of the patients had partial response, 30% complete response after two courses, and 60% of CR after four courses. Supratentorial and infratentorial tumors had a good response to chemotherapy. Brainstem tumors had an initial response after two courses and then increased in size. AA was the tumor with the greatest reduction of residual tumor after treatment. Overall and free survival at 53 months was 70%. To date, three patients have died secondary to tumoral progression. There have been no relapses in the seven patients with a CR. Conclusions Postoperative chemotherapy with ICE reduces the tumor size and increases the survival rate of pediatric patients with malignant astrocytomas with minimal toxicity. Brain- stem responded poorly to treatment.