Authors: David A Reardon Annick Desjardins Katherine B Peters Sridharan Gururangan John H Sampson Roger E McLendon James E Herndon Anuradha Bulusu Stevie Threatt Allan H Friedman James J Vredenburgh Henry S Friedman
Publish Date: 2011/10/11
Volume: 107, Issue: 1, Pages: 155-164
Abstract
We evaluated the efficacy of carboplatin irinotecan and bevacizumab among bevacizumabnaïve recurrent glioblastoma GBM patients in a phase 2 openlabel single arm trial Forty eligible patients received carboplatin area under the plasma curve AUC 4 mg/mlmin on day one while bevacizumab 10 mg/kg and irinotecan 340 mg/m2 for patients on CYP3Aenzymeinducing antiepileptics EIAEDs and 125 mg/m2 for patients not on EIAEDs were administered on days 1 and 14 of every 28day cycle Patients were evaluated after each of the first two cycles and then after every other cycle Treatment continued until progressive disease unacceptable toxicity noncompliance or voluntary withdrawal The primary endpoint was progressionfree survival at 6 months PFS6 and secondary endpoints included safety and median overall survival OS All patients had progression after standard therapy The median age was 51 years Sixteen patients 40 had a KPS of 90–100 while 27 68 were at first progression The median time from original diagnosis was 114 months The PFS6 rate was 465 95 CI 304 610 and the median OS was 83 months 95 confidence interval CI 59 and 107 months Grade 4 events were primarily hematologic and included neutropenia and thrombocytopenia in 20 and 10 respectively The most common grade 3 events were neutropenia thrombocytopenia fatigue and infection in 25 20 13 and 10 respectively Eleven patients 28 discontinued study therapy due to toxicity and 17 patients 43 required dose modification One patient died due to treatmentrelated intestinal perforation The addition of carboplatin and irinotecan to bevacizumab significantly increases toxicity but does not improve antitumor activity to that achieved historically with singleagent bevacizumab among bevacizumabnaïve recurrent GBM patients ClinicalTrialsgov number NCT00953121
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