phase I trial using combination irinotecan and thalidomide for recurrent CNS
Adler, F. C. Lee
of New Mexico, Albuquerque, NM
Irinotecan inhibits topoisomerase I.
Several clinical studies indicate efficacy against primary brain tumors.
Thalidomide is a novel anti-cytokine agent with secondary anti-angiogenesis
Both drugs in combination pose a rational approach to treating recurrent primary
This Phase I study seeks to determine maximum treatment dosages of thalidomide
in combination with a fixed dose of irinotecan.
Treatment regimen includes Irinotecan 300mg/m2 iv over 30 minutes on day 1 of a
21-day cycle followed by thalidomide po qhs days 3-19 starting at 200mg and
escalating weekly at 100 mg increment to a maximum tolerable dose.
To date, 4 patients have been enrolled: 3 with anaplastic oligodendrogliomas and
1 with anaplastic astrocytoma.
One patient died after 2 cycles, without thalidomide escalation, due to
One patient was removed from protocol after 2 cycles due to a question of
disease progression, but reached a thalidomide dose of 500mg.
A third patient completed 4 cycles and reached a thalidomide dose of 600mg but
with Grade III neuropathy requiring a dose reduction.
The fourth patient has completed 15 cycles with marked reduction in tumor size
and improvement in clinical status, but required a lengthening of the treatment
cycle to every 4-5 weeks due to Grade III neutropenia and dose reduction of
thalidomide due to Grade II-III fatigue.
Other toxicities included drowsiness, peripheral neuropathy and muscle weakness,
but were tolerated by patients.
All patients reported no diarrhea.
Radiographic response was demonstrated in 3 patients with a response rate of
Median duration of response is 69 days with the exception of one patient who is
still undergoing active treatment after 14 months at the time of reporting.
Data are limited but the combination of irinotecan and thalidomide seems to have
good activity in certain patients with recurrent primary brain tumors and
deserves further evaluation.
Thalidomide seems to alleviate the potential gastrointestinal side effects from
high dose irinotecan used in this regimen.
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American Society of Clinical Oncology All rights