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High Dose Tamoxifen and Radiotherapy in Patients with Glioblastoma Multiforme: A Phase IB Study

Published online by Cambridge University Press:  02 December 2014

Thierry Muanza ,
George Shenouda ,
Luis Souhami ,
Robert Corns ,
Richard Leblanc ,
Gerard Mohr  and
Adrian Langleben
Thierry Muanza
Affiliation:
Departments of Oncology, Division of Radiation Oncology, McGill University, Montreal, Quebec, Canada
George Shenouda
Affiliation:
Departments of Oncology, Division of Radiation Oncology, McGill University, Montreal, Quebec, Canada
Luis Souhami
Affiliation:
Departments of Oncology, Division of Radiation Oncology, McGill University, Montreal, Quebec, Canada
Robert Corns
Affiliation:
Departments of Oncology, Division of Radiation Oncology, McGill University, Montreal, Quebec, Canada
Richard Leblanc
Affiliation:
Department of Neuro-Surgery, McGill University, Montreal, Quebec, Canada
Gerard Mohr
Affiliation:
Department of Neuro-Surgery, McGill University, Montreal, Quebec, Canada
Adrian Langleben
Affiliation:
Department of Medicine, McGill University, Montreal, Quebec, Canada
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Abstract

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Purpose:

To assess the feasibility and the toxicity of adjuvant high dose tamoxifen (TAM) and postoperative brain irradiation for patients with newly-diagnosed glioblastoma multiforme (GBM).

Material and Methods:

Twelve patients with histopathologically confirmed GBM entered the study. There were nine males and three females, with median age of 48.8 years (range 30-75 years). Karnofsky performance status (KPS) was 60-70% for four patients and 80-100% for eight patients. Based on the Radiation Therapy Oncology Group recursive partition analysis, there were three class III patients, six class IV, one class V, and two class VI. Eleven patients underwent partial surgical tumor resection and one patient had a near complete resection. Two weeks post surgery, the patients were started on high dose TAM (120mg/m2 P.O. BID for three months). Two weeks from date of starting TAM, external beam radiotherapy (RT) was given at a dose of 59.4 Gy/33 qd fractions/6.5 weeks. Patients were assessed weekly for toxicity during treatment. Imaging studies were done at the end of two weeks of TAM, then monthly.

Results:

Median follow-up was 40 weeks (range 22-84 weeks). In one patient, TAM was associated with significant vomiting, necessitating the TAM dose to be decreased at three weeks and then stopped at two months. One other patient had bilateral deep venous thrombosis after 51/2 weeks on TAM, although the relationship to TAM was not firmly established. There were no radiological responses after two weeks of TAM or at the end of RT. The median time to progression was 17.7 weeks (range 5.1- 43.8 weeks). Median survival time was 33.4 weeks (range 10-79.7). Actuarial survival at 48 and 74 weeks was 40% and 15%, respectively.

Conclusion:

Our study shows that adjuvant high dose TAM is feasible and relatively well-tolerated. Furthermore, the combined use of high dose TAM and RT postoperatively was not associated with any significant increase in radiation-induced neurological toxicity. However, high dose TAM does not appear to improve treatment results.

Résumé:

RÉSUMÉ:Objectif:

Évaluer la praticabilité et la toxicité d'un traitement adjuvant par le tamoxifène à haute dose (TAM) et la radiothérapie cérébrale chez les patients ayant un diagnostic récent de glioblastome multiforme (GBM).

Matériel et Méthodes:

Douze patients ayant un GBM confirmé par anatomopathologie ont été recrutés. Il s'agissait de neuf hommes et trois femmes dont l'âge médian était de 48.8 ans (fourchette de 30 à 75 ans). L'indice de Kamofsky était de 60 à 70% chez quatre patients et de 80 à 100% chez huit patients. Selon l'analyse de partition récursive du Radiation Therapy Oncology Group, il y avait trois patients de classe III, six de classe IV, un de classe V et deux de classe VI. Onze patients ont subi une résection chirurgicale partielle et un patient a subi une résection presque complète de la tumeur. Deux semaines après la chirurgie, on a commencé à administrer le TAM à haute dose (120 mg/m2 p.o. b.i.d. pendant trois mois). Deux semaines après le début du TAM, un traitement de radiothérapie externe (RT) a été administré pour une dose totale de 59.4 Gy/33 q.d. fractionnée sur 6.5 semaines. Les patients étaient évalués à chaque semaine quant à la toxicité du traitement. Des études d'imagerie ont été réalisées après deux semaines de TAM et mensuellement par la suite.

Résultats:

La durée médiane de suivi était de 40 semaines (fourchette de 22 à 84 semaines). Chez un patient, le TAM a été associé à des vomissements importants nécessitant une réduction de la posologie du TAM après trois semaines de traitement et un arrêt après deux mois. Un autre patient a présenté une thrombophlébite profonde bilatérale après 5%2 semaines de TAM, bien que la relation avec le TAM n'ait pas été établie avec certitude. Il n'y a pas eu de réponse radiologique après deux semaines de TAM ou à la fin de la RT. Le temps médian jusqu'à la progression était de 17.7 semaines (fourchette de 5.1 à 43.8 semaines). La survie moyenne était de 33.4 semaines (fourchette de 10 à 79.7 semaines). La survie actuarielle à 48 et 74 semaines était de 40% et 15% respectivement.

Conclusion:

Notre étude démontre qu'un traitement d'appoint par le TAM est faisable et relativement bien toléré. De plus, l'utilisation combinée de doses élevées de TAM et de radiothérapie postopératoire n'était pas associée à une augmentation significative de la toxicité neurologique induite par la radiothérapie. Cependant, le TAM à haute dose ne semble pas améliorer les résultats du traitement.

Type
Research Article
Information
Canadian Journal of Neurological Sciences , Volume 27 , Issue 4 , November 2000 , pp. 302 - 306
Copyright
Copyright © The Canadian Journal of Neurological Sciences Inc. 2000

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