VI Autologous Bone Marrow Transplantation.pdf - Blog Science ...

3. Conclusion
In conclusion, treatment with HD BCNU can be ethically considered in patients
with high grade glioma since the toxicity is mild and the toxic death rate
of the whole program is under 10%. After BCNU, patients can be monitored as
out patients. Results remain poor for the whole group but quality of life is acceptable
during the first year. Results are encouraging for patients with grade III
astrocytomas. This procedure is still proposed for patients with a macroscopically
complete resection of grade III astrocytomas. For other patients with residual
tumor after surgery (grade III and IV), we designed a phase I-II trial of
high dose fotemustine, a new nitrosurea compound with significant efficacy on
high grade glial tumors in phase II trial at conventional doses ( 7
).
PHASE Ml TRIAL OF HIGH DOSE FOTEMUSTIN (HDF) FOLLOWED BY ABMT IN
HIGH GRADE GLIOMAS.
Fotemustin is a new nitrosurea with a significant antitumor activity in
glioma. A response rate of 36% has recently been reported in patients with high
grade gliomas at conventional doses (lOOmg/ m 2
/week, 3 weeks) ( 7
).
This phase I-II trial was designed to determine the feasibility and tolerance
of high (supraconventional) doses of fotemustin given with autologous marrow
support in patients with high grade glioma. The second objective was to evaluate
the antitumor activity of fotemustin in this setting.
1- Patients and methods:
1.1- Description of the patients.
Inclusion criteria were: age under 65 years, high grade astrocytoma with an
évaluable residual tumor mass.
Twenty-five patients were included in this trial between April 1988 and
May 1991 in the Centre Leon Berard. The median age was 43 with a range of 21
to 62.18 were males, 7 were females.
13 had glioblastoma, 3 had grade TV astrocytoma, 5 had grade 3
astrocytoma, 3 had a high grade oligodendroglioma, 1 had a sarcomatous
glioblastoma.
Primary surgery was a macroscopically complete excision in 2 patients,
wide excision in 14, partial excision in 2 and stereotaxic biopsy in 7. Performance
status according to the ECOG scale were as follows: ECOG 0: 7, ECOG 1:10,
ECOG 2:5, ECOG 3: 3.
1.2- Description of the study
Treatment plan was comparable to that of HD-BCNU concerning
cytoreductive surgery, monitoring after ABMT and radiation therapy. Bone
marrow harvested was stored in liquid nitrogen until the date of ABMT.
Fotemustin was begun 48 hours after bone marrow harvest. Fotemustin was
given in one hour infusion in two consecutive days. Half of the total dose was
given day 1 and 2. The first dose level was twice the conventional dose: 600mg/
m 2
. Dose increase was 100 mg/m 2
for each level. The upper level was reached
only if less than 2 grade 3 or 4 extrahematological toxicities were observed at the
previous level. The hematological toxicity was not limitative for dose increment.5
patients were included at the 600mg/m 2
and 700mg/m 2
levels.4 patients
218 SIXTH INTERNATIONAL SYMPOSIUM ON AUTOLOGOUS BONE MARROW TRANSPLANTATION