YMI--full text abstract
RESULTS OF A PHASE II TRIAL OF H-R3 MONOCLONAL ANTIBODY (NIMOTUZUMAB) IN THETREATMENT OF RESISTANT OR RELAPSED HIGH-GRADE GLIOMAS IN CHILDREN ANDADOLESCENTS
Fleischhack, G.1; Buchen, S.1; Bach, F.2; Bode, U.11 Universitätsklinikum, Bonn; 2 Oncoscience AG, Wedel
Background: Children and adolescents suffering from high grade gliomas (HGG) have a poor prognosis when they relapse during or after primary treatment. Thus novel therapeutic approaches as the inhibition of growth-signalling pathways are needed. This multicentre phase II trial was designed toexplore the feasibility and efficacy of the h-R3 monoclonal anti-EGFR antibody (Nimotuzumab) in thetreatment of these patients.
Patients and Methods: Pediatric patients with glioblastoma multiforme, anaplastic astrocytoma orintrinsic pontine glioma (PG) with radiologically proven progressive disease following primary orrelapse treatment were eligible to the study. The treatment consisted of an induction therapy including a weekly short infusion of 150 mg/m² Nimotuzumab for six weeks, and in case of non-PD a subsequent consolidation therapy of four infusions in a three week interval. The response was documented by MRI in week 8 and 21.
Results: Between June 2004 and August 2005 34 patients aged 5.0 to 17.4 years (median 10.9years) were enrolled in this study. According to RECIST 12 out of 34 patients showed response (PRn=1, SD n=11) in the MRI of week 8 after the induction therapy with a median change in the largest diameter of the index lesion of -5% (-39 to +16%) accompanied by clinical deterioration in four and markedly clinical improvement in two patients. Surprisingly 9 PR/SD were seen in the 14 patients with PG. Eight patients continued with the consolidation therapy. So far 5 out of 8 Patients are evaluable for response after consolidation therapy and showed three PR, one SD and one PD in week 21. Eight patients with consolidation therapy are free of progression for a median of 7.5 months (1.2-13.2 months). No severe side effects related to the study medication were observed.
Conclusions: These data suggest that the repeated application of Nimotuzumab is well tolerated and safe. It has cytotoxic efficacy in heavily pre-treated relapsed HGG, especially in intrinsic pontineglioma. A phase III study for patients with newly diagnosed PG is warranted.
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