Phase II study of irinotecan in combination with temozolomide (TEMIRI) in children with recurrent or refractory medulloblastoma: a joint ITCC and SIOPE brain tumor study

作者：Grill Jacques^*; Geoerger Birgit; Gesner Lyle; Perek Danuta; Leblond Pierre; Canete Adela; Aerts Isabelle; Madero Luis; de Toledo Codina Josep Sanchez; Verlooy Joris; Estlin Edward; Cisar Laura; Breazna Aurora; Dorman Andrew; Bailey Simon; Nicolin Gary; Grundy Richard G; Hargrave Darren

来源：Neuro-Oncology, 2013, 15(9): 1236-1243.

DOI：10.1093/neuonc/not097

• medulloblastoma
• temozolomide
• TEMIRI

This multicenter phase II study investigated temozolomide irinotecan (TEMIRI) treatment in children with relapsed or refractory medulloblastoma. %26lt;br%26gt;Patients received temozolomide 100125 mg/m(2)/day (days 15) and irinotecan 10 mg/m(2)/day (days 15 and 812) every 3 weeks. The primary endpoint was tumor response within the first 4 cycles confirmed 4 weeks and assessed by an external response review committee (ERRC). In a 2-stage Optimum Simon design, 6 responses in the first 15 evaluable patients were required within the first 4 cycles for continued enrollment; a total of 19 responses from the first 46 evaluable patients was considered successful. %26lt;br%26gt;Sixty-six patients were treated. Seven responses were recorded during stage 1 and 15 in the first 46 ERRC evaluated patients (2 complete responses and 13 partial responses). The objective response rate during the first 4 cycles was 32.6 (95 confidence interval [CI], 19.548.0). Median duration of response was 27.0 weeks (7.744.1 wk). In 63 patients evaluated by local investigators, the objective response rate was 33.3 (95 CI, 22.046.3), and 68.3 (95 CI, 55.379.4) experienced clinical benefit. Median survival was 16.7 months (95 CI, 13.319.8). The most common grade 3 treatment-related nonhematologic adverse event was diarrhea (7.6). Grade 3/4 treatment-related hematologic adverse events included neutropenia (16.7), thrombocytopenia (12.1), anemia (9.1), and lymphopenia (9). %26lt;br%26gt;The planned study primary endpoint was not met. However, its tolerability makes TEMIRI a suitable candidate chemotherapy backbone for molecularly targeted agents in future trials in this setting.

• 出版日期2013-9