Bj. Fisher et al., Phase I study of topotecan plus cranial radiation for glioblastoma multiforme: Results of Radiation Therapy Oncology Group Trial 9507, J CL ONCOL, 19(4), 2001, pp. 1111-1117
Purpose: A phase I trial was conducted by the Radiation Therapy Oncology Gr
oup (RTOG) to determine the maximum-tolerated dose of topotecan that could
be safely combined with standard cranial radiation for glioblastoma multifo
rme. A secondary objective was to document the acute and late toxicities of
this combination of chemotherapy and radiation.
Patients and Methods: Forty-seven patients with histologically confirmed gl
ioblastoma multiforme were entered onto this phase I trial. Three cycles of
topotecan were administered at 21-day intervals commencing at day 1 of cra
nial radiotherapy (60 Gy/30 fractions). Each cycle consisted of daily 30-mi
nute intravenous (IV) infusions for 5 days. The dose of tapotecan was escal
ated in three-dose increments from 0.5 mg/m(2)/d to 1.0 mg/m(2)/d to 1.5 mg
/m(2)/d in different patient groups.
Results: The majority of patients were over age 50. Three dose levels of to
potecan were tested. Fifteen patients accrued to level 1 (topotecan dose 0.
5 mg/m(2)/d). No grade 4 toxicities were seen. Sixteen patients accrued to
level 2 (topotecan dose 1.0 mg/m(2)/d), five of whom had brief episodes of
grade 4 neutropenia. Seventeen patients accrued to level 3 (1.5 mg/m(2)/d).
Six of these patients had brief episodes of grade 4 neutropenia and four d
eveloped grade 3 thrombocytopenia. No serious nonhematologic or late toxici
ties were seen. Median survival for all patients was 9.7 months. There was
no apparent difference in survival by topotecan dose schedule.
Conclusion: Toxicity was acceptable at an IV topotecan dose of 1.5 mg/m(2)/
d administered daily for 5 days every 21 days for three cycles. A phase II
trial has been performed using this dose of topotecan.