Outcome of patients with glioblastoma multiformae (GBM), treated with pre-radiation chemotherapy and concomitant chemoradiation followed by post-radiation treatment using continuous low dose temozolomide schedule

Abstract

1577 Rationale: To study the effect of low dose daily temozolomide in non-irradiated patients with resected GBM, in view of the possibly improved drug delivery prior to radiation induced changes in the tumor bed. Continuous administration schedule was based on the fact that, continuous exposure to temozolomide has shown to deplete the enzyme responsible for acquisition of drug resistance. This is a single institution phase II study with planned enrollment of 10 patients. Method: Patients who underwent near total excision of their GBM were started on temozolomide 75 mg/m2/day for six weeks given on an eight-week cycle. Patients were given one cycle prior to radiation therapy, followed by concomitant chemo-radiation and the same schedule of chemotherapy continued post- radiation, until tumor progression. Patients underwent weekly blood count and monthly MRI throughout the treatment. Results: The first 2 patients enrolled showed progression during the pre-radiation phase, and the protocol was amended to start radiation concommitantly with the first cycle of chemotherapy. There was high incidence of prolonged grade 4 neutropenia and bilateral lung infiltrates, including one death from progressive sepsis. Conclusion: Even though phase II and III studies have shown survival benefit for using temozolomide during radiation therapy, caution should be exercised in the elderly and immunosuppressed patients. Appropriate prophylactic antibiotic therapy is essential in these patients. Future studies should include correlation with biological markers, not only to predict response, but also to attempt to identify patients at high risk for toxicity. The continuous administration schedule provides higher cumulative drug dose, likely resulting in excess toxicity than the bolus regimen and the latter schedule may be preferrable in the post radiation phase. In summary, our study supports that the continuous schedule temozolomide has activity with brain radiation, but this schedule was ineffective as a pre-radiation therapy, and also appears to be associated with excessive toxicity with prolonged use. No significant financial relationships to disclose.