Successful treatment of childhood astrocytomas with cisplatin and irinotecan

Abstract

9508 Background: Childhood astrocytomas are a heterogeneous group of neoplasms for which non-surgical management is controversial. After a pilot study suggesting that irinotecan/cisplatin (I/C) may be effective for spinal cord astrocytomas in children (Mora et al, Neuro-Oncol 2007), we initiated a phase II trial for progressing astrocytomas with the aim of avoiding radiation therapy for low grade's and improve outcome for high grade's. Methods: The indication for adjuvant therapy was based upon histology, the extent of surgical resection, and the presence of clinical or neuroradiological signs of progression. Weekly Irinotecan (50 mg/m2 and 65 mg/m2 the last 2 cycles) and Cisplatin (30 mg/m2) for four consecutive weeks (1 cycle), and a total of 4 cycles was used. Results: Since 2004, 17 children aged 7m-17y were treated including 5 WHO grade I, 6 grade II, 3 grade III, and 3 non biopsied tumors: 2 intrinsic brain-stem tumors (BST) and 1 optic-pathway (OP) tumor. No patient had clinical signs of neurofibromatosis. Primary sites included 4 supratentorial, 3 BST, 3 OP, 1 cerebellar, and 6 spinal tumors. Gross total resection was performed in 1 case, subtotal in 4 and only biopsy in 9. Six patients received chemotherapy and one radiotherapy prior to the I/C regimen. Vomiting was easily controlled except for patients with BST. All but 2 patients, because of C allergy, completed the protocol with no documented ototoxic, renal, or GI side effects. Eleven (65%) pts had a complete clinical response, including 1 BST and all the spinal cord cases. Remarkably all the clinical responses were rapid, within the first 1–2 weeks of treatment. Twelve (70%) pts had a <25 [O1] % reduction of the tumor size at the end of therapy including 2 spinal cord cases that achieved complete radiological responses 10 months after the end of therapy. One BST patient progressed on therapy. Thus far, none of the low grade cases have received radiotherapy, although median f/u is only 1 year. All pts are alive and well. Conclusions: Remarkable clinicoradiological responses and avoidance of radiotherapy was obtained using the I/C regimen for childhood astrocytoma. No significant financial relationships to disclose.