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Randomized multicenter phase II trial of irinotecan and bevacizumab as neoadjuvant and adjuvant to temozolomide-based chemoradiation versus chemoradiation for unresectable glioblastoma: Interim results of the TEMAVIR study from the ANOCEF group.
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2011
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ImmunotherapeuticsHigh-grade GliomasControl ArmGliomaRelapsed GbmNeuro-oncologyOncologyMetronomic TherapyAnti-cancer AgentClinical Radiation OncologyRadiation OncologyMolecular OncologyCancer ResearchRadiologyHealth SciencesAnocef GroupRadiation TherapyInterim ResultsCancer TreatmentPharmacologyExperimental ArmMedicineTemavir Study
2029^ Background: The prognosis of unresectable glioblastoma (GBM) remains poor despite temozolomide- based chemoradiation with a median of 6 month progression-free survival (PFS). Activity of bevacizumab/irinotecan has been reported in patients with relapsed GBM (Vredenburgh, 2007). The objective of this randomized phase II trial was to evaluate the efficacy and safety of irinotecan (IRI) and bevacizumab (BVZ) as neo-adjuvant and adjuvant treatment to chemoradiation with temozolomide (TMZ) and BVZ for naive unresectable glioblastoma. Control arm was TMZ as concomitant and adjuvant treatment to radiation. Methods: Pts with de novo unresectable GBM, aged 18-70, and KPS > 50, and EORTC RPA class 5 were eligible. Experimental arm (A) consisted of neo-adjuvant BVZ 10 mg/kg and IRI 125 mg/m2, every 2 wk for 4 cycles before radiotherapy 60 Gy in 30 fractions with concurrent TMZ 75 mg/m2/day and BVZ every 2 wk. Adjuvant BVZ and IRI were given every 2 wk for 6 month. The control arm (B) consisted of concomitant TMZ 75 mg/m2/d during radiotherapy and 150-200 mg/m2 for 5 d every 28 d for 6 month. Cross over were allowed for progression. The inclusion of 67 pts/arm was planned, using Fleming’s 2 steps design aiming at an increase of PFS at 6 month (PFS6) from 50 % to 66 %, with unilateral alpha 5% and 80% power. Results: Patients (134) were included from April 2009 to January 2011. Clinical factors were well balanced between arms. At interim analysis 6 month after inclusion of the first 30 pts in arm A, 17 were alive and free of progression (57%). In arm B, 13 patients were alive and free of progression (43%). Four deaths were related to treatment in arm A (3 cerebral haemorrhages, 1 peritonitis) and 0 in arm B. According to Fleming’s rules it was required to include 30 pts more in arm A for final analysis. Conclusions: Interim results suggest that experimental arm could reach efficacy hypotheses based on the favourable trend in PFS. The risk of severe cerebral haemorrhage due to BVZ appears as unusually high in this patient population. Updated results will be presented at the meeting.