Autologous Bone Marrow Transplantation - Blog Science Connections

High-Dose Therapy of CNS Gliomas
Table 1. Summary of High-Dose Studies
Phase Drug Total Dose (mg/m 2 ) Dose/day (mg/m 2 ) Schedule
I Thio-TEPA 180-1575 60-525 Days -6, -5,--4
I Carmustine and 1050 350 Days -8, -7,--6
etoposide 1200-2400 400-800 Days -5, -4,--3
II Carmustine 1050-1350 350-450 Days -5, -4,--3
II Etoposide 2400 800 Days -5, -4,--3
III Carmustine 900-1050 300-350 Days -5, -4, -3
"Autologous bone marrow transplantation was performed on day 0.
Table 2. Summary of Phase I and II Responses
Response
Median Survival
Study n No. % 95% Cl a Time (mo)
Carmustine 27 12 44 28-63 5
Etoposide 16 3 19 5-30 4
Carmustine and
etoposide 4 0 0 0-50 3
Thio-TEPA 4 1 25 5-70 2+
a
95% confidence intervals.
RESULTS
Thio-TEPA
We have recently completed phase I evaluation of high-dose thio-TEPA
and are now conducting a phase II study (7). The initial total dose
administered was 180 mg/m 2
(60 mg/m 2 /day for 3 days) and the highest
dose has been 1575 mg/m 2
(525 mg/m 2 /day for 3 days). To date, only four
patients with tumors of the CNS have been treated on the phase II study; one
has responded. Toxicities of thio-TEPA have been predominantly myelosuppression,
mucositis, and dermatologie reaction; a novel CNS toxicity has
been noted at the higher dose levels.
Carmustine
Twenty-seven patients with progressive malignant gliomas after maximal
radiation therapy were treated with high-dose carmustine at a dose of
1050-1350 mg/m 2 (350-450 mg/m 2 /day for 3 days). Responses were
noted in 12 patients (44%) (8). The median survival time of all patients was 5
months; two were alive and apparently disease-free at 60 and 84 months after
transplantation. Toxicities in this study were predominantly nonhematologic,
including hepatic, pulmonary, and CNS. The overall rate of fatal nonhematologic
toxicity was 17%.