Efficacy of Temozolomide Treatment in Patients with High-grade Glioma

تاریخ : ۱۳۹۳/۰۶/۳۰ / تعداد بازدید : ۳۵۵

Abstract

Background:

Numerous studies have reported the clinical efficacy of temozolomide (TMZ) treatment for highgrade glioma, but information on Japanese populations has been limited. This study assessed the safety and early outcomes of TMZ treatment, with or without combination therapy.

Patients and Methods:

The subjects comprised ten patients with high-grade glioma [glioblastoma multiforme (GBM), n=3, gliosarcoma (GS), n=1, anaplastic oligodendroglioma (AO), n=3, anaplastic mixed oligoastrocytoma (AOA), n=1, and anaplastic ependymoma (AE), n=2]. All the patients were initially treated with conventional radiotherapy following surgical resection with or without adjuvant chemotherapy. As second- or third-line chemotherapy, patients received TMZ for recurrence or tumor progression. As combination therapy, the local administration of tumor necrosis factor-alpha and the addition of carboplatin and etoposide were included for three patients during the course of oral TMZ treatment.

Results:

Partial response (PR) to TMZ therapy was achieved by four out of the ten patients (objective response rate, 40% ), while three patients displayed stable disease (SD) and three showed disease progression (PD).

One of the patients receiving combination therapy has continued to show shrinkage of the relapsed tumor. Despite prior radio- and chemotherapy, most patients experienced only grade 1-2 hematotoxicity that was well controlled by conservative therapy.

Conclusion:

TMZ chemotherapy is effective for the treatment of high-grade glioma in some patients without serious toxicity. Assessing the true efficacy of TMZ will require a larger study with comparison of longterm outcomes between other agents or combined therapeutic modalities.

High-grade gliomas, among the most common primary brain tumors, are very aggressive tumors with poor prognosis despite a multi-modal treatment approach including extensive surgery, radiotherapy and nitrosourea-based chemotherapy (1, 2). Recurrence of high-grade glioma is associated with significant morbidity and limited survival.

The majority of patients have already received multimodal therapy including surgery, radiotherapy and chemotherapy at initial diagnosis. Generally, conventional radiotherapy cannot be added when relapse occurs, and the therapeutic options are thus limited to further resection or adjuvant chemotherapy. Such adjuvant chemotherapy has been considered to have modest efficacy in a recurrent setting (3).

Temozolomide (TMZ) is an alkylating agent with excellent oral bioavailability, good penetration across the blood-brain barrier and a low toxicity profile (4). In 2001 the presentation of Phase II data for TMZ in addition to radiotherapy as first-line adjuvant therapy against glioblastoma multiforme (GBM) demonstrated a markedly improved 2-year survival rate compared to historical series(5). This was confirmed in a subsequent Phase III study, which reported an improvement in 2 year survival to 26% from 10% with radiotherapy alone (6). Since then, many studies have demonstrated antitumor activity of TMZ in the treatment of newly diagnosed or recurrent high-grade glioma (3, 7) and it is currently expected to improve the poor prognosis for such patients (8, 9). Furthermore, the oral formulation of TMZ is likely to be more acceptable to these patients, compared to systemic intravenous administration.

Recent reports have focused on the development of strategies to optimize the clinical efficacy of TMZ using different dosing schedules and combination with other antineoplastic agents (10, 11). In Japanese populations, however, limited information has been available regarding TMZ treatment for high-grade glioma, including GBM (12). The present study sought to elucidate the safety and feasibility of TMZ treatment and examined the early outcome data for patients with high-grade glioma who had previously received conventional radiotherapy with or without other combination therapy.

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Efficacy of Temozolomide Treatment in Patients with High-grade Glioma

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