Autologous Bone Marrow Transplantation - Blog Science Connections

560 High-Dose Therapy of CHS Gliomas
Etoposide
Sixteen patients have been treated on a phase II study with high-dose
etoposide administered at a dose of 2400 mg/m 2 (800 mg/m 2 /day for 3
days). All patients had progressive gliomas after prior maximal radiation
therapy, and half had been exposed previously to carmustine. Three
responses provided an overall response rate of 19% (9). The median survival
time of the entire group was 4 months; the three responders lived 9,10, and
54+ months. Toxicity of this treatment was predominantly myelosuppression;
nonhematologic toxicity was modest.
Carmustine and Etoposide
In this study, high-dose carmustine at the maximal dose of 1050 mg/m 2
(350 mg/m 2 /day for 3 days) was combined with high-dose etoposide at two
dose levels, 1200 mg/m 2 and 2400 mg/m 2 (400 and 800 mg/m 2 /day for 3
days) (10). Three patients were treated at the first level and one patient at the
second. No responses were noted, and the study was stopped because of the
severe hepatic toxicity that occurred in two patients. The median survival
time of all patients was 3 months from transplantation.
Adjuvant Carmustine
High-dose carmustine at a dose of 900-1050 mg/m 2 (300-350
mg/m 2 /day for 3 days) was administered to 18 patients with glioblastoma
multiforme or anaplastic astrocytoma shortly after they completed standard
radiation therapy (11). Toxicity of this study was predominantly pulmonary
and included four fatal episodes. The actuarial probability of survival of the
entire group was 19% at 27 months after diagnosis. At present, four patients
are alive but two have recurrent and progressive tumor. Two patients are
apparently long-term disease-free survivors at 60 and 77 months from
diagnosis, the former patient is well but the latter is severely neurologically
compromised owing to severe encephalomyelopathy (12). The actuarial
probability of survival for all patients is shown in Figure 1.
DISCUSSION
Primary tumors of the CNS are a formidable challenge due to their
inherent drug resistance and the pharmacologic sanctuary of the blood-brain
barrier. High-dose chemotherapy can overcome inadequate CNS penetration
and, if a dose-response relationship exists, can overcome relative drug
resistance. For these reasons, treatment of CNS tumors with high-dose
chemotherapy and ABMT has been actively studied. In this report, we
summarize our collaborative systematic program of evaluating high-dose
therapy for tumors of the CNS in phase 1, II, and III studies.
Carmustine avidly crossed the blood-brain barrier and is the most active
agent for treating CNS tumors. Using the criteria of Wilson et ai, the