Phase II study of topotecan in patients with recurrent malignant glioma. National Clinical Institute of Canada Clinical Trials Group.
BACKGROUND
The NCIC Clinical Trial Group has an ongoing interest in assessing investigational agents in minimally pretreated patients with malignant glioma. Topotecan is one of the first topoisomerase I inhibitors to enter clinical trials and has shown early evidence of activity in several solid tumors. We have conducted a phase II trial of topotecan in patients with malignant glioma.


METHODS
Adults with malignant glioma and recurrent contrast enhancing measurable disease (> or = 2 x 2 cm) were eligible. Topotecan 1.5 mg/m2 i.v. was given daily x five days every three weeks. Response and toxic effects were assessed at the end of each cycle.


RESULTS
Thirty-one patients were entered onto the study: fifteen had glioblastoma, 16 anaplastic astrocytoma, all had prior radiation, 15 prior chemotherapy, and all were assessable for response and toxicity. Two patients (6%) responded: one had a complete radiographic response, but died with neutropenic sepsis, and the second had a prolonged partial response (> 97 weeks). Twenty-one patients (68%) had stable disease for five to 86 + weeks (median 19) and eight (26%) had progressive disease after one cycle. Toxicity was primarily hematologic; 18 (58%) had grade 4 neutropenia (< 0.5 x 10(9)/1), usually brief, and three (10%) grade 4 thrombocytopenia (< 25 x 10(9)/1). Twelve of 109 cycles (11%) were given at reduced dose.


CONCLUSIONS
Topotecan in this dose and schedule has only modest activity in recurrent glioblastoma and anaplastic astrocytoma.
Macdonald
D
D
Department of Clinical Neurological Sciences, University of Western Ontario, London, Kingston, Canada.
Cairncross
G
G
Stewart
D
D
Forsyth
P
P
Sawka
C
C
Wainman
N
N
Eisenhauer
E
E
D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D001254:Astrocytoma / Q000188:drug therapy* / Q000473:pathology; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000473:pathology; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D005909:Glioblastoma / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000473:pathology; D019772:Topotecan; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D019772:Topotecan; D002166:Camptothecin