Pre-targeted locoregional radioimmunotherapy with 90Y-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 90Y-biotin in the locoregional radioimmunotherapy (RIT) of recurrent high grade glioma, and to investigate the antitumor efficacy of this new treatment. Twenty-four patients with recurrent glioma underwent second surgical debulking and implantation of a catheter into the surgical resection cavity (SRC), in order to introduce the radioimmunotherapeutic agents [biotinylated monoclonal antibody (MoAb), avidin and 90Y-biotin]. Eight patients with anaplastic astrocytoma (AA) and 16 patients with glioblastoma (GBM) were injected with biotinylated anti-tenascin MoAb (2 mg), then with avidin (10 mg; 24 h later) and finally 90Y-biotin (18 h later). Each patient received two of these treatments 8-10 weeks apart. The injected activity 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 tolerated without acute side effects up to 0.740 GBq (20 mCi). The maximum tolerated activity was 1.110 GBq (30 mCi) limited by neurological toxicity. None of the patients developed hematologic toxicity. In three patients infection occurred around the catheter. The average absorbed dose to the normal brain was minimal compared with that received at the SRC interface. At first control (after 2 months), partial (PR) and minor (MR) responses were observed in three GBM (1 PR; 2 MR) and three AA patients (1 PR; 2 MR) with an overall objective response rate of 25%. Stable disease (SD) was achieved in seven GBM and five AA patients (50%). There was disease progression in six GBM 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 produced an objective response in 25% of patients. Based on these encouraging results, phase II studies employing 3-S-RIT soon after first debulking are justified.

[1]  B. Wessels,et al.  131I-Lym-1 in mice implanted with human Burkitt's lymphoma (Raji) tumors: loss of tumor specificity due to radiolysis. , 2000, Cancer biotherapy & radiopharmaceuticals.

[2]  H. Engelhard,et al.  The role of interstitial BCNU chemotherapy in the treatment of malignant glioma. , 2000, Surgical neurology.

[3]  P. Bondiau,et al.  Up-front chemotherapy with fotemustine (F) / cisplatin (CDDP) / etoposide (VP16) regimen in the treatment of 33 non-removable glioblastomas. , 2000, European journal of cancer.

[4]  M. Adamo,et al.  Role of nuclear medicine in the treatment of malignant gliomas: the locoregional radioimmunotherapy approach , 2000, European Journal of Nuclear Medicine.

[5]  F. D. De Braud,et al.  Antibody-guided three-step therapy for high grade glioma with yttrium-90 biotin , 1999, European Journal of Nuclear Medicine.

[6]  H. Sakahara,et al.  The relationship of glycosylation and isoelectric point with tumor accumulation of avidin. , 1999, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[7]  M. Ferrari,et al.  Three-step radioimmunotherapy with yttrium-90 biotin: dosimetry and pharmacokinetics in cancer patients , 1999, European Journal of Nuclear Medicine.

[8]  J. Dempsey,et al.  Dosimetric properties of a novel brachytherapy balloon applicator for the treatment of malignant brain-tumor resection-cavity margins. , 1998, International journal of radiation oncology, biology, physics.

[9]  R. Coleman,et al.  Iodine-131-labeled antitenascin monoclonal antibody 81C6 treatment of patients with recurrent malignant gliomas: phase I trial results. , 1998, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[10]  K. Hopkins,et al.  Direct injection of 90Y MoAbs into glioma tumor resection cavities leads to limited diffusion of the radioimmunoconjugates into normal brain parenchyma: a model to estimate absorbed radiation dose. , 1998, International journal of radiation oncology, biology, physics.

[11]  E. Oldfield,et al.  Tumor regression with regional distribution of the targeted toxin TF-CRM107 in patients with malignant brain tumors , 1997, Nature Medicine.

[12]  L. Lopalco,et al.  Three-step monoclonal antibody tumor targeting in carcinoembryonic antigen-positive patients. , 1991, Cancer research.

[13]  A. Ahlbom,et al.  BRAIN TUMOUR TRENDS , 1989, The Lancet.

[14]  E. Oldfield,et al.  Intratumoral LAK cell and interleukin-2 therapy of human gliomas. , 1989, Journal of neurosurgery.

[15]  R K Jain,et al.  Mechanisms of heterogeneous distribution of monoclonal antibodies and other macromolecules in tumors: significance of elevated interstitial pressure. , 1988, Cancer research.

[16]  C. Meares,et al.  Pre-targeted immunoscintigraphy of murine tumors with indium-111-labeled bifunctional haptens. , 1988, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[17]  H. Hoffman,et al.  Extraneural metastases of central nervous system tumors , 1985, Cancer.

[18]  A. Walker,et al.  Epidemiology of brain tumors , 1985, Neurology.

[19]  Fred H. Hochberg,et al.  Assumptions in the radiotherapy of glioblastoma , 1980, Neurology.

[20]  D. Larson,et al.  Radiotherapy of primary malignant brain tumors. , 1998, Seminars in surgical oncology.

[21]  B. Fisher,et al.  Supratentorial malignant glioma: patterns of recurrence and implications for external beam local treatment. , 1992, International journal of radiation oncology, biology, physics.