Although the standard of care for patients with glioblastoma multiforme (GM) remains postoperative radiotherapy (RT) in combination with chemotherapy (CT), the optimal regimen awaits verification. A phase I study was performed to determine the dose limiting toxicity (DLT) and the maximum tolerated dose (MTD) of topotecan (Hycamptin), given concurrently with RT, in patients with previously untreated glioblastoma multiforme (GM) of the brain. Thirty-six patients with histologically confirmed GM

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... re enrolled. After surgery or stereotactic biopsy, patients received conventional external cranial RT (59.4 Gy/33 fractions in 6.6 weeks). Two cycles of topotecan were administered at days 1 and 4 of each week. Each cycle consisted of 30-min intravenous infusion 30-60 min before RT. The dose of topotecan was escalated in three dose increments from 1.0 to 1.25 and 1.5 mg/m 2 on a twice a week schedule among different patient groups. Three dose levels of topotecan were tested. Ten patients accrued to level 1 (topotecan dose 1 mg/m 2 /day, twice a week). No grade 4 toxicities were seen. Grade 2/3 hematologic toxicity was observed in 4 patients. Of the 11 patients included at level 2 (topotecan dose 1.25 mg/m 2 /day twice a week), 3 presented with grade 3 leucopenia and 2 with grade 3 thrombocytopenia. Of the 15 patients accrued to level 3 (topotecan dose 1.5 mg/m 2 , twice a week), six had episodes of grade 4 leucopenia and two developed grade 4 thrombocytopenia. No other serious, early non-hematologic or late toxicities were seen at 21 months median follow-up time (range 6-36 months). From the cases included at level 2 and 3, five patients experienced episodes of grade 2/3 asthenia (13.8%), headache 9 (25%), confusion 5 (13.8%), seizure 4 (11%), and cutaneous erythema 3 (8.3%). The DLTs of topotecan given concurrently with RT were mainly hematological and the MTD was determined at the 1.25 mg/m 2 /day, twice a week dose level. A phase II chemoradiation study using the above recommended MTD dose of topotecan is ongoing, to establish the response rates, the local failures and the median survival of the above patients.