Initial experience with locoregional radioimmunotherapy using ¹³¹I-labelled monoclonal antibodies against tenascin (BC-4) for treatment of glioma (WHO III and IV)

Summary

Aim: None of the established treatments (surgery, radiotherapy, chemotherapy) for malignant glioma has improved its very poor prognosis. Adjuvant locoregional radioimmunotherapy (RIT) represents a new therapeutic approach. We present our initial experience with this therapeutic tool with respect to adverse effects, biokinetics and clinical follow-up. Methods: Following surgery and radiotherapy, 12 patients with glioma (4, WHO stage III; 8, WHO stage IV) underwent 1-5 RIT-cycles (average dose 1100 MBq ¹³¹labelled monoclonal BC-4 antibodies) at six week intervals. Follow-up included serial FDG-PET and MRI investigations. Evaluation of biokinetics included whole body scans, together with analysis of blood, urine and fluid from the tumor cavity. Results: Following RIT, four patients experienced temporary seizures, which, in one case, were associated with temporary aphasia. Eight patients developed HAMA (human anti-mouse antibodies) during follow-up. Mean biologic half-life of the radiopharmaceutical in the resection cavity was 3.9 d (range: 1.0-10.2 d) and remained stable intraindividually during further RIT-cycles. The antibody/radionuclide conjugate remained stable in the tumor cavity for at least 5 d. Median survival presently stands at 18.5 months compared to 9.7 months in a historical patient group (n = 89) undergoing conventional therapeutic strategies. Five patients show no signs of recurrence. In three patients with post-surgical evidence of residual tumor, one patient showed partial remission, one stable disease, and one progressive disease during RIT. Four patients without evidence of residual tumor mass at the beginning of RIT developed recurrence during therapy. Conclusions: Initial experience demonstrates that locoregional RIT is a well tolerated treatment modality that may represent a promising new approach in the management of patients with malignant glioma. Advantages of local application include passage of the blood-brain barrier, high concentration of activity within the resection cavity and low systemic toxicity.

Zusammenfassung

Ziel: Bei der Standardtherapie von Gliomen (Resektion, Radiatio, Chemotherapie) ist die Prognose sehr schlecht. Ein neuer Therapieansatz besteht in der additiven lokalen Radioimmuntherapie (RIT) mit ¹³¹I-markierten Tenascin- Antikörpern (BC-4). Diese Studie berichtet über unsere initialen Erfahrungen hinsichtlich Nebenwirkungen, Biokinetik und klinischem Verlauf. Methoden: Zwölf Patienten (4 Gliome WHO III, 8 Gliome WHO IV) erhielten nach Operation und perkutaner Radiatio 1-5 RIT-Zyklen im Abstand von 6 Wochen mit durchschnittlich 1100 MBq ¹³¹I-markierten Antikörpern über ein Ommaya-Reservoir. Der Verlauf wurde durch FDG-PET- und MRT-Untersuchungen dokumentiert. Die Biokinetik wurde an Ganzkörperaufnahmen, Blut- und Urinproben sowie Proben aus der Tumorhöhle nach RIT beurteilt. Ergebnisse: Unter RIT traten bei vier Patienten passagere Anfälle, bei einem in Kombination mit transienter Sprachstörung auf. Acht Patienten bildeten im Verlauf HAMAs (humane Antikörper gegen Mausantigen) aus. Die biologische HWZ der Aktivität in der Tumorhöhle lag im Mittel bei 3,9 d (1,0-10,2 d) und blieb intraindividuell bei Folgetherapien konstant. Das Radioimmunkonjugat in der Tumorhöhle blieb mindestens 5 d stabil. Die mittlere Überlebenszeit liegt zurzeit bei 18,5 Monaten und ist damit deutlich höher als bei einer historischen Patientengruppe mit Standardtherapie (9,7 Monate; n = 89). Fünf Patienten zeigen bisher keinen Hinweis auf ein Rezidiv. Bei drei Patienten mit einem Tumorrest nach Operation zeigte sich unter RIT in einem Fall partielle Remission, ein stabiler und ein progredienter Krankheitsverlauf. Vier Patienten ohne Tumorrest zu Therapiebeginn entwickelten unter Therapie ein Rezidiv. Schlussfolgerungen: Erste Erfahrungen mit der lokalen RIT zeigen, dass diese komplikationsarme Therapieform additiv zur Standardtherapie ein Erfolg versprechender Ansatz bei malignem Gliom ist. Vorteile liegen in der Umgehung der Bluthirnschranke, der hohen lokalen Aktivitätskonzentration und der niedrigen systemischen Toxizität.

Keywords

Glioblastoma - astrocytoma - radioimmunotherapy - BC-4 antibodies

Schlüsselwörter

Glioblastom - Astrozytom - Radioimmuntherapie - Tenascin-Antikörper - BC-4-Antikörper

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