Second-line chemotherapy with temozolomide in recurrent oligodendroglioma after PCV (procarbazine, lomustine and vincristine) chemotherapy: EORTC Brain Tumor Group phase II study 26972
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/m(2) 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