Pre-targeted locoregional radioimmunotherapy with 9(0Y)-biotin in glioma patients: Phase I study and preliminary therapeutic results

The aim of this study was to determine the maximum-tolerated dose, of a pre -targeting three-step (3-S) method employing Y-90-biotin in the locoregiona l radioimmunotherapy (RIT) of recurrent high grade glioma, and to investiga te the antitumor efficacy of this new treatment. Twenty-four patients with recurrent glioma underwent second surgical debulk ing and implantation of a catheter into the surgical resection cavity (SRC) , in order to introduce the radioimmunotherapeutic agents [biotinylated mon oclonal antibody (MoAb), avidin and Y-90-biotin]. Eight patients with anaplastic astrocytoma (AA) and 16 patients with gliobl astoma (GBM) were injected with biotinylated anti-tenascin MoAb (2 mg), the n with avidin (10 mg; 24 h later) and finally Y-90-biotin (18 h Inter). Eac h patient received two of these treatments 8-10 weeks apart. The injected a ctivity ranged from 0.555 to 1.110 GBq (15-30 mCi). Dosage was escalated by 0.185 GBq (5 mCi) in four consecutive groups. The treatment was well toler ated without acute side effects up to 0.740 GBq (20 mCi). The maximum toler ated activity was 1.110 GBq (30 mCi) limited by neurological toxicity. None of the patients developed hematologic toxicity. In three patients infectio n occurred around the catheter. The average absorbed dose to the normal bra in was minimal compared with that received at the SRC interface. At first control (after 2 months), partial (PR) and minor (MR) responses we re observed in three GEM (1 PR; 2 MR) and three AA patients (1 PR; 2 MR) wi th an overall objective response rate of 25%. Stable disease (SD) was achie ved in seven GEM and five AA patients (50%). There was disease progression in six GEM patients (25%), but in none of the AA patients. At the dosage of 0.7-0.9 GBq per cycle, locoregional 3-S-RIT was safe and p roduced an objective response in 25% of patients. Based on these encouragin g results, phase II studies employing 3-S-RIT soon after first debulking ar e justified.