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

• DOI: 10.1093/neuonc/not097
• Publication Date: 2013-07-15T21:08:54Z
• Authors: J. Grill; B. Geoerger; L. Gesner; D. Perek; P. Leblond; A. Canete; I. Aerts; L. Madero; J. S. de Toledo C...; J. Verlooy; E. Estlin; L. Cisar; A. Breazna; A. Dorman; S. Bailey; G. Nicolin; R. G. Grundy; D. Hargrave
• Keywords: Tolerability; Temozolomide; Clinical endpoint; Leukopenia

This multicenter phase II study investigated temozolomide + irinotecan (TEMIRI) treatment in children with relapsed or refractory medulloblastoma.Patients received 100-125 mg/m(2)/day (days 1-5) and 10 1-5 8-12) every 3 weeks. The primary endpoint was tumor response within the first 4 cycles confirmed ≥4 weeks assessed by an external review committee (ERRC). In a 2-stage Optimum Simon design, ≥6 responses 15 evaluable patients were required for continued enrollment; total of 19 from 46 considered successful.Sixty-six treated. Seven recorded during stage 1 ERRC evaluated (2 complete 13 partial responses). objective rate 32.6% (95% confidence interval [CI], 19.5%-48.0%). Median duration 27.0 (7.7-44.1 wk). 63 local investigators, 33.3% CI, 22.0%-46.3%), 68.3% 55.3%-79.4%) experienced clinical benefit. survival 16.7 months 13.3-19.8). most common grade treatment-related nonhematologic adverse event diarrhea (7.6%). Grade 3/4 hematologic events included neutropenia (16.7%), thrombocytopenia (12.1%), anemia (9.1%), lymphopenia (9%).The planned not met. However, its tolerability makes TEMIRI suitable candidate chemotherapy backbone molecularly targeted agents future trials this setting.