Efficacy of postoperative chemotherapy using cisplatin plus etoposide in young children with brain tumors

Abstract

Neuraxis radiation therapy (RT) for primary intracranial tumors is associated with major late effects if administered to very young children. To control residual tumor and to delay RT, we treated eight young children (median age 6.5 months) with primary central nervous system (CNS) tumors using combination chemotherapy: cisplatin, 20 mg/M2/day plus VP-16, 75 mg/M2/day i.v. for 5 days, given q. 3-6 weeks for 8 cycles. The tumors were medulloblastoma (one), malignant ependymoma (two), primitive neuroectodermal tumor PNET (two), malignant glioma (two), astrocytoma (one). Six had measurable disease; three had positive cerebrospinal fluid (CSF) cytopathology. All patients with measurable tumor had initial objective responses (three) complete response [CR], one partial response [PR], two minor response [MR], including cytopathology (three CR of three) and metastatic deposits (two CR of two). One patient relapsed during chemotherapy. Median time to disease progression was 17.5 months; median survival was 34 months. Three patients, none of whom received RT, have prolonged progression-free intervals of 47-67 months to date. Neurodevelopmental progress continued during and after chemotherapy. Chemotherapy toxicity was mild. Median neutrophil nadir was 312/mm3, platelets 72,000. Fever during neutropenia occurred in six of 61 courses. Moderate high-frequency auditory losses were detected in three patients, and mild renal injury (GFR less than 70 ml/min) was detected in two of seven evaluable children. This pilot study demonstrates the apparent efficacy and mild toxicity of 5 day courses of cisplatin plus VP-16, with delayed RT, in young children with CNS neoplasms. A POG treatment protocol that incorporates cisplatin plus VP-16 is evaluating primary chemotherapy with delayed radiotherapy in larger numbers of pediatric brain tumor patients.

Prolonged Second Response to Cisplatin, Etoposide, and Ifosfamide in a Child With a Recurrent Brainstem Glioblastoma

“…Cisplatin (20 mg/m 2 /d for 5 days) and etoposide (75 mg/m 2 /d for 5 days) have been combined for the deferral or postponement of radiotherapy among infants with malignant central nervous system tumors. Among malignant gliomas, primitive neuroectodermal tumors, and ependymomas, the complete response rate was 38% and the partial response rate was 13% [9]. Etoposide has also been combined with ifosfamide with demonstrated ef® cacy in recurrent pediatric brain tumors [10].…”

An intensive multiagent chemotherapy regimen for brain tumours occurring in very young children.

“…Children treated on the study were followed to time of radiotherapy, relapse or death 0-6 7-12 13-18 [19][20][21][22][23][24] 25-30 31-36 37-42 43-48 49-54 through the data monitoring service of the UKCCSG.…”

Preclinical evaluation of 9-chloro-2-methylellipticinium acetate alone and in combination with conventional anticancer drugs for the treatment of human brain tumor xenografts

“…Since cisplatin and etoposide (see below) are two agents reported to be useful as adjuvant therapy in the treatment of brain tumors (Yoshida et al 1993;Strauss et al 1991), these compounds were evaluated alone and in combination with CME. When cisplatin was given at a dose of 7.5 mg/kg i.v.…”