Treatment of childhood glial tumors with cisplatin and irinotecan

Abstract

10062 Background: Childhood glial tumors are heterogeneous neoplasias for which non-surgical management is controversial. After a pilot study suggesting that irinotecan/cisplatin (I/C) may be effective in children (Mora et al, Neuro Oncol 2007), we initiated a phase II prospective trial with the aim of avoiding radiation therapy for low grade's (LG) and improve outcome for high grade's (HG). 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: From January 2004 to December 2007, 30 children aged 6 months to 17 years were treated, 21 at diagnosis, 7 at progression and 2 at relapse. Fourteen tumors were WHO grades I-II gliomas (LGG), 10 grade III (6 gliomas, 2 anaplastic ependymomas and 2 AT/RT), and 6 had no biopsy (3 brainstem (BST) and 3 optic-pathway tumors (OPT)). Two patients had type-1 neurofibromatosis and OPT. Primary sites included: 4 supratentorial, 8 BST, 9 OPT, 2 cerebellar, and 7 spinal. Prior to the I/C regimen, gross total resection was performed in 7 and biopsy in 14 tumors; 9 patients received chemotherapy and 5 radiotherapy. All but 6 patients, 2 because of C allergy and 4 BST because of progression, completed the protocol, with no grade 3–4 side effects. Vomiting was the main side effect. Twenty (90%) of 22 patients with evaluable clinical symptoms had a complete and rapid response, with objective functional recovery. With a median follow-up of 25 months, 14 (47%) patients had a complete/partial response (7 out of 10 HG), 10 (40%) had stable disease (8 out of 14 LG), and 6 (20%) progressed (all BST). Five patients died of disease, all BST. Twenty-five (83%) patients remain progression-free, median 27 months from protocol entry. Conclusions: Seventy percent objective response rate for HG and avoidance of radiotherapy for 93% of LG was obtained using the I/C regimen. Remarkable fast clinical responses and functional recoveries occurred. No significant financial relationships to disclose.