Pilot study of vincristine, oral irinotecan, and temozolomide (VOIT regimen) combined with bevacizumab in pediatric patients with recurrent solid tumors or brain tumors

摘要

Background: The combination of vincristine, oral irinotecan, and temozolomide (VOIT regimen) has shown antitumor activity in a pediatric Phase I trial. To further potentiate synergy, we assessed the safety and feasibility of adding bevacizumab to VOIT for children and young adults with recurrent tumors. Methods: Patients received vincristine (1.5mg/m2 on day 1), oral irinotecan (90mg/m2 on days 1-5), temozolomide (100-150mg/m2 on days 1-5), and bevacizumab (15mg/kg on day 1) in 3-week cycles, which were repeated for up to six cycles. Cefixime prophylaxis was used to reduce irinotecan-associated diarrhea. Results: Thirteen patients received 36 total cycles. Six of the first 10 patients required dose reductions due to toxicity during the first cycle (n=3) or subsequent cycles (n=3), and these grade 3 side effects included prolonged nausea, dehydration, anorexia, neuropathy, diarrhea, and abdominal pain, as well as prolonged grade 4 neutropenia. After reducing daily temozolomide to 100mg/m2, three additional patients tolerated therapy well without the need for dose reductions. Toxicities attributed to bevacizumab were limited to grade 1 epistaxis (1) and grade 2 proteinuria (1). Tumor responses were seen in both patients with Ewing sarcoma. Conclusions: Reducing temozolomide from 150 to 100mg/m2/day improved tolerability, and treatment with this lower temozolomide dose was feasible and convenient as outpatient therapy. Although responses were seen in Ewing sarcoma, the benefit of adding bevacizumab remains unclear.