Clinical studyBCNU as second line therapy for recurrent high-grade glioma previously treated with Temozolomide
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.
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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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Cited by (11)
The use of chemotherapy in patients with gliomas: Patterns of care in Victoria from 1998-2000
2008, Journal of Clinical NeuroscienceCitation Excerpt :Temozolomide is now a “standard of care” for patients with recurrent high-grade gliomas and its use is also standard in conjunction with post-operative radiotherapy for those patients with newly diagnosed GBM.2–5 There is less data available to recommend second and subsequent lines of chemotherapy in the recurrent setting although the use of BCNU, carboplatin and other drugs is commonplace.8 Our study reviewed the use of chemotherapy in glioma patients between 1998–2000 in Victoria.
Therapeutic options for recurrent high-grade glioma in adult patients: Recent advances
2006, Critical Reviews in Oncology/HematologyGlioblastoma: Epidemiology, risk factors, diagnosis, and treatment options
2012, Glioblastoma: Risk Factors, Diagnosis and Treatment OptionsEfficacy of protracted dose-dense temozolomide in patients with recurrent high-grade glioma
2011, Journal of Neuro-OncologyEvolution of care for patients with relapsed glioblastoma
2011, Expert Review of Anticancer Therapy