High dose tamoxifen and radiotherapy in patients with glioblastoma multiforme: A phase IB study

Purpose: To assess the feasibility and the toxicity of adjuvant high dose t amoxifen (TAM) and postoperative brain irradiation for patients with newly- diagnosed glioblastoma multiforme (GBM). Material and methods: Twelve patie nts with histopathologically confirmed GEM entered the study. There were ni ne males and three females, with median age of 48.8 years (range 30-75 year s). Karnofsky performance status (KPS) was 60-70% for four patients and 80- 100% for eight patients. Based on the Radiation Therapy Oncology Group recu rsive partition analysis, there were three class III patients, six class TV , one class V, and two class VI, Eleven patients underwent partial surgical tumor resection and one patient had a near complete resection, Two weeks p ost surgery, the patients were started on high dose TAM (120mg/ m(2) P.O. B ID for three months). Two weeks from date of starting TAM, external beam ra diotherapy (RT) was given at a dose of 59.4 Gy/33 qd fractions/6.5 weeks. P atients were assessed weekly for toxicity during treatment. Imaging studies were done at the end of two weeks of TAM, then monthly. Results: Median fo llow-up was 40 weeks (range 22-84 weeks). In one patient, TAM was associate d 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 aft er 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 (ra nge 10-79.7), Actuarial survival at 48 and 74 weeks was 40% and 15%, respec tively. 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 no t appear to improve treatment results.