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Annals of Oncology 14:599-602, 2003
© 2003 European Society for Medical Oncology

Original Paper

Second-line chemotherapy with temozolomide in recurrent oligodendroglioma after PCV (procarbazine, lomustine and vincristine) chemotherapy: EORTC Brain Tumor Group phase II study 26972

M. J. van den Bent1,+, O. Chinot2, W. Boogerd3, J. Bravo Marques4, M. J. B. Taphoorn5, J. M. Kros6, C. C. D. van der Rijt7, C. J. Vecht8, N. De Beule9 and B. Baron9

Departments of 1 Neuro-Oncology, 6 Pathology and 7 Medical Oncology, University Hospital Rotterdam/Rotterdam Cancer Center, The Netherlands; 2 CHU de la Timone, Marseilles, France; 3 Netherlands Cancer Institute, Amsterdam, The Netherlands; 4 IPO Francisco Gentil, Lisbon, Portugal; 5 Department of Neurology, University Medical Center Utrecht, The Netherlands; 8 Department of Neurology, Medical Center Haaglanden/Westeinde, The Hague, The Netherlands; 9 European Organisation for Research and Treatment of Cancer Data Center, Brussels, Belgium

Received 5 July 2002; revised 21 October 2002; accepted 21 November 2002

Background:

Oligodendroglial tumors are chemosensitive, with two-thirds of patients responding to PCV combination chemotherapy with procarbazine, lomustine (CCNU) and vincristine. Temozolomide (TMZ), a new alkylating and methylating agent has shown high response rates in recurrent anaplastic astrocytoma. We investigated this drug in recurrent oligodendroglial tumors (OD) and mixed oligoastrocytomas (OA) after prior PCV chemotherapy and radiation therapy.

Patients and methods:

In a prospective non-randomized multicenter phase II trial patients were treated with TMZ 150 mg/m2 on days 1–5 in cycles of 28 days for 12 cycles. Eligible patients had a recurrence after prior PCV chemotherapy, with measurable and enhancing disease as shown by magnetic resonance imaging. Pathology and all responses were centrally reviewed.

Results:

Thirty-two eligible patients were included. In four patients the pathology review did not confirm the presence of an OD or OA. Twelve of 24 patients [50%, 95% confidence interval (CI) 29% to 71%] evaluable for response to first-line PCV chemotherapy had responded to PCV. Temozolomide was in general well tolerated; the most frequent side-effects were hematological. One patient discontinued treatment due to toxicity. In seven of 28 patients (25%, 95% CI 11% to 45%) with histologically confirmed OD an objective response to TMZ was observed. Median time to progression for responding patients was 8.0 months. After 6 and 12 months from the start of treatment, 29% and 11% of patients, respectively, were still free from progression.

Conclusions:

TMZ may be regarded as the preferred second-line treatment in OD after failure of PCV chemotherapy. Further studies on TMZ in OD are indicated.

Key words: chemotherapy, oligoastrocytoma, oligodendroglioma, recurrent, second line, temozolomide


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