|
|
Fotemustine
combined with procarbazine in recurrent malignant gliomas: a phase I study with
evaluation of lymphocyte 06-alkylguanine-DNA alkyltransferase activity
Boiardi A, Silvani A, Ciusani E, Watson A, Margison G,
Berger E, Lucas C, Giroux B
Istituto Carlo Besta, Milan, Italy
The aims
of this phase I study in patients with recurrent malignant gliomas were to
determine the maximum tolerated dose (MTD) and toxicity profile of fotemustine
when combined with a fixed dose of procarbazine (PCZ), and to evaluate the
extent of O6-alkylguanine-DNA alkyltransferase (ATase) depletion in circulating
lymphocytes during treatment.
Sixteen patients received an induction cycle consisting of 100 mg/day oral PCZ
for 12 consecutive days and a 1-h intravenous infusion of fotemustine given 4 h
after PCZ on days 5 and 12 at escalated doses (50, 75, 100 and 125 mg/m2/day).
After a 6-week rest period, a maximum of 4 maintenance cycles (PCZ 300 mg/day, 4
days; fotemustine, day 4) was given every 4 weeks.
ATase activity was measured on days 1, 5 and 12 over 4 h after PCZ intake.
Fifteen patients had previously received at least one nitrosourea-based
chemotherapy, associated with PCZ in 12 cases.
The MTD of fotemustine was 125 mg/m2 (days 5 and 12) with myelosuppression as
the dose limiting toxicity (DLT).
At this dose level, half of patients experienced grade 3 anemia, neutropenia or
thrombopenia.
No extra-hematological DLT was observed.
No significant depletion of ATase activity by PCZ was evidenced.
One partial response and 7 stable diseases were obtained leading to a disease
control rate of 50%.
The median times to progression and survival were 2.6 and 9.7 months,
respectively.
This combined regimen of PCZ and fotemustine was well tolerated with a good
disease control rate in heavily pretreated glioma patients and merits further
investigation in phase II studies.
PMID:
11508814 [PubMed - indexed for MEDLINE]
Source:
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11508814&dopt=Abstract
|
