Efficacy of bevacizumab plus irinotecan in children with recurrent low-grade gliomas--a Pediatric Brain Tumor Consortium study

Gururangan, S.; Fangusaro, J.; Poussaint, T. Y.; McLendon, R. E.; Onar-Thomas, A.; Wu, S.; Packer, R. J.; Banerjee, A.; Gilbertson, R. J.; Fahey, F.; Vajapeyam, S.; Jakacki, R.; Gajjar, A.; Goldman, S.; Pollack, I. F.; Friedman, H. S.; Boyett, J. M.; Fouladi, M.; Kun, L. E.

Neuro Oncol. 2013 Dec 7; 16(2):310-7

Abstract

BACKGROUND: A phase II study of bevacizumab (BVZ) plus irinotecan (CPT-11) was conducted in children with recurrent low-grade glioma to measure sustained response and/or stable disease lasting >/=6 months and progression-free survival. METHODS: Thirty-five evaluable patients received 2 doses (10 mg/kg each) of single-agent BVZ intravenously 2 weeks apart and then BVZ + CPT-11 every 2 weeks until progressive disease, unacceptable toxicity, or a maximum of 2 years of therapy. Correlative studies included neuroimaging and expression of tumor angiogenic markers (vascular endothelial growth factor [VEGF], VEGF receptor 2, hypoxia-inducible factor 2alpha, and carbonic anhydrase 9). RESULTS: Thirty-five evaluable patients (median age 8.4 y [range, 0.6-17.6]) received a median of 12 courses of BVZ + CPT-11 (range, 2-26). Twenty-nine of 35 patients (83%) received treatment for at least 6 months. Eight patients progressed on treatment at a median time of 5.4 months (range, 1-17.8). Six patients (17.7%) still in follow-up have had stable disease without receiving additional treatment for a median of 40.1 months (range, 30.6-49.3) from initiating therapy. The 6-month and 2-year progression-free survivals were 85.4% (SE +/- 5.96%) and 47.8% (SE +/- 9.27%), respectively. The commonest toxicities related to BVZ included grades 1-2 hypertension in 24, grades 1-2 fatigue in 23, grades 1-2 epistaxis in 18, and grades 1-4 proteinuria in 15. The median volume of enhancement decreased significantly between baseline and day 15 (P < .0001) and over the duration of treatment (P < .037). CONCLUSION: The combination of BVZ + CPT-11 appears to produce sustained disease control in some children with recurrent low-grade gliomas.

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