RESUMEN

We investigated the putative benefits of simultaneous teleradiotherapy and anti-epidermal growth factor receptor (EGFR) 125I monoclonal antibody (MAb) 425 radioimmunotherapy, when applied after neurosurgery in high-grade gliomas, over teleradiotherapy alone. In comparison to previous studies which have reported good results with this type of radioimmunotherapy, we advanced the adjuvant radioimmunotherapy step, that is, gave it during, not after, teleradiotherapy. The randomized prospective study examined two groups: simultaneous postoperative teleradiotherapy and radioimmunotherapy (TRT + RIT; eight patients) versus teleradiotherapy alone (TRT; 10 patients). Patients who after primary operation of grade III (6 cases) or IV glioma (12 cases), showed no or less than 2 mL of remnant tumor on post-operative magnetic resonance (MR) study and were not treated postoperatively by chemotherapy were enrolled and randomized. Anti-EGFR 125IMAb 425 RIT was started during week 4 of radiotherapy, not later than 8 weeks after neurosurgery, and was repeated three times at 1-week intervals. Total activity given was 5026 + 739 MBq/patient. The tolerance of TRT was good. No immediate side effects of concomitant anti-EGRF 125I RIT were observed. Observation showed a median total survival (as evaluated from the primary neurosurgical treatment) of 14 months (range 3.5-28 months). There was no improvement in disease-free or total survival in the group of patients treated by TRT + RIT after neurosurgery. In addition, an immunohistochemical analysis of EGFR expression in gliomas was performed in a group of 100 cases and was distinctly positive in 50% grade IV gliomas and 68% grade III gliomas. We conclude that simultaneous radiotherapy and radioimmunotherapy with anti-EGFR 125I-MAb 425 is not beneficial over radiotherapy alone in adjuvant treatment of high-grade gliomas after neurosurgery. We also recommend individual confirmation of EGFR expression in further anti-EGFR radioimmunotherapy trials.

Asunto(s)

Anticuerpos Monoclonales/uso terapéutico , Receptores ErbB/inmunología , Glioma/inmunología , Glioma/radioterapia , Radioinmunoterapia , Adulto , Animales , Receptores ErbB/biosíntesis , Receptores ErbB/genética , Femenino , Glioma/patología , Humanos , Radioisótopos de Yodo/uso terapéutico , Masculino , Ratones , Ratones Endogámicos BALB C , Persona de Mediana Edad , Estadificación de Neoplasias , Índice de Severidad de la Enfermedad , Proteína Tumoral Controlada Traslacionalmente 1

RESUMEN

BACKGROUND: In this paper we present the preliminary results of a prospective trial of the efficacy of simultaneous radiotherapy and anti-EGFR (125)I radioimmunotherapy of malignant gliomas with 2 years' total survival as the end-point, raising the question whether anti-EGFR (125)I radioimmunotherapy influences the disease-free survival in these patients. MATERIAL AND METHODS: Patients with anaplastic astrocytoma or primary glioblastoma were previously treated by a macroscopically radical neurosurgical approach and randomized either to radiotherapy + radioimmunotherapy arm or treated by radiotherapy alone. Seven patients were included in the group with radioimmunotherapy, among them five with GBM and two with AA, and five patients in the control arm. Patients were irradiated to 60 Gy using three-dimensional conformal noncoplanar techniques. Anti-EGFR (125)I monoclonal antibody 425 radioimmunotherapy (50 mCi/course) was started during 4th week of radiotherapy and was repeated three times in one week intervals. RESULTS: Time of follow-up ranges between 2 and 10 months in the anti-EGFR (125)I radioimmunotherapy arm and 4 and 9 months in the control arm. Recurrence was diagnosed in all patients in the EGFR (125)I group with a lethal outcome in two of them and in 4 patients in the control group. Median time to recurrence was 2 and 5 months respectively. CONCLUSIONS: Taking into account early recurrences observed, we propose to continue the studies on the efficacy of adjuvant anti-EGFR (125)I radioimmunotherapy in a selected group of patients in whom the greatest benefit may be expected on the basis of molecular studies, among them EGFR expression investigation.