Temozolomide phase II study in children with relapsing refractory high-risk neuroblastoma

9012 Background: To determine the response rate (RR) of neuroblastoma (NB) in children to temozolomide (TMZ), and evaluate the duration of response and tolerance of the drug in this patient population. Methods: A multicenter, phase II evaluation of an oral, daily schedule of TMZ (200 mg/m2 on 5 consecutive days and repeated every 28 days) was undertaken in children with a refractory or relapsed high-risk NB (metastatic or localized with Myc-N amplification). Evidence of activity was defined by radiologic or MIBG scan evidence of sustained reduction in lesion size or activity whenever it occurs. Methodology included a two-step study using Fleming's method with a first step of 15 patients and a second of 10 additional patients if 2 to 4 responses had been observed in the first cohort. All data were centrally reviewed by a panel. Results: Among 34 registered patients over a 14 month period in 14 centres, twenty five are finally evaluable and received 94 cycles of chemotherapy. Disease status was metastatic NB (n=23) either refractory (n=9) or in relapse (n=14). Grade [3/4] thrombocytopenia was the most frequent toxic event (16% of the cycles). Myelosuppression resulted in significant treatment delays and dose reductions (24% and 21% of cycles respectively). Out of 25 patients, response (CR, VGPR or PR) was observed in 5 (RR=20 {+/-} 8%) with a median duration of 6 months. Furthermore a mixed response or an objective effect was observed in respectively 2 and 3 additional patients. Conclusions: Temozolomide is effective in heavily pretreated patients with NB, and deserves further evaluation in combination with another drug No significant financial relationships to disclose.