Phase II trial of SarCNU in malignant glioma: unexpected pulmonary toxicity with a novel nitrosourea: a phase II trial of the national cancer institute of canada clinical trials group

Abstract

Purpose: A multi-centre phase II study of SarCNU-a novel chloroethylnitrosourea (CNU)-in patients with recurrent malignant glioma to assess response rate, survival and effects of treatment.

Patients and methods: Ten patients with histologically proven malignant glioma (seven with glioblastoma multiforme (GBM) and three with anaplastic astrocytoma) received SarCNU (860 mg/m(2)) orally on days 1, 5 and 9 on a 6 week schedule.

Results: A total of ten patients were treated on protocol before accrual was suspended for a high rate of pulmonary toxicity. Of eight evaluable patients, five demonstrated at least one grade deterioration in DLCO from baseline. This necessitated premature closure of the trial. Stable disease was seen in five of seven evaluable patients (median duration 4.8 months; range 0.8-9.2) with progressive disease in the remainder.

Conclusion: Despite promising preclinical data, SarCNU caused pulmonary toxicity in patients with recurrent malignant glioma and we plan no further studies in this indication.