Clinical study
BCNU as second line therapy for recurrent high-grade glioma previously treated with Temozolomide

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Abstract

BCNU has an established role in the treatment of high-grade gliomas and has previously been used as first line therapy for recurrent disease. More recently, Temozolomide has taken its place as first line therapy for recurrent high-grade glioma. Thus, BCNU has become our standard second line therapy following disease progression after Temozolomide therapy. This study retrospectively analysed the activity and toxicity associated with BCNU as second line therapy. Twenty four patients with recurrent high-grade gliomas were treated with BCNU having previously received Temozolomide. Patients received BCNU intravenously at 130–200 mg/m2 every 6 weeks. The median number of treatment cycles was two (range 1–8). Of the 24 patients, one patient (4%) achieved a partial response and six (25%) achieved a minor response or stable disease. BCNU was generally well tolerated. In conclusion, BCNU has limited activity as second line chemotherapy following the use of Temozolomide. Novel strategies are required in this patient group.

Introduction

High-grade gliomas represent 1–2% of all adult cancers and 2% of all cancer deaths in the adult population.1 At initial diagnosis, a multi-modality treatment approach includes surgery, radiotherapy and chemotherapy. The role of adjuvant chemotherapy remains controversial with data suggesting a modest survival benefit at best.2 Palliative chemotherapy at disease recurrence following surgery and radiotherapy may provide disease stabilisation or regression. Previously, chemotherapy such as the nitrosoureas and procarbazine-based regimens had modest activity and significant toxicity when used in the setting of recurrent high-grade gliomas.[3], [4], [5] Newer agents or combinations of agents have been recently evaluated in the treatment of recurrent gliomas.[3], [4], [5]

Temozolomide is an alkylating agent administered orally that readily crosses the blood–brain barrier and has confirmed activity and tolerability.[6], [7] Indeed, Temozolomide has become our standard chemotherapy in patients with recurrent high-grade glioma. Our own evaluation of efficacy and toxicity proved comparable with international data.8 Inevitably, patients receiving Temozolomide develop disease progression and the choice of second line therapy remains uncertain. Routinely we have used BCNU in this setting. This retrospective study was designed to assess the efficacy and tolerability of BCNU as second line therapy following the use of Temozolomide in patients with recurrent high-grade gliomas.

Section snippets

Methods

A total of 24 patients with high-grade gliomas were treated within two institutions (Austin and Repatriation Medical Centre and Royal Melbourne Hospital, Victoria). Patients with histologically confirmed glioblastoma multiforme or anaplastic astrocytoma (GBM or AA) according to WHO criteria were eligible.9 All patients had previously undergone post-resection irradiation and received Temozolomide at disease progression. No patient had received adjuvant chemotherapy or other chemotherapy for

Results

All 24 patients were evaluable for response and 23 were evaluable overall survival. The solitary patient not evaluable for survival data had returned overseas with known progressive disease and was lost to follow-up. Table 1 summarises the baseline characteristics of all patients. The patient group was relatively young with a median age of 55 years and of good performance status. Twenty patients (83%) had GBM and the remainder had an AA.

Prior to commencing BCNU, five patients (21%) had

Discussion

Recurrence of high-grade gliomas is associated with significant morbidity and limited survival. Most patients will have already received multi-modality therapy including surgery, radiotherapy and on occasions, chemotherapy, at initial diagnosis. Generally, radiotherapy cannot be administered at recurrence and thus the therapeutic options are limited to further resection or palliative chemotherapy.

Palliative chemotherapy has previously been considered to have modest efficacy in the recurrent

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