Trea
tmen
t op
tions for lep
tomeningeal dissemina
ted brain
tumors are limi
ted by
the lack of effec
tive drugs for in
tra
thecal
therapy of non-hema
tologic malignancies. We repor
t on our experience wi
th an in
traven
tricular
therapy consis
ting of mafosfamide, a preac
tiva
ted cyclophosphamide deriva
tive, and e
toposide. Be
tween May 1994 and 2002, 26 pa
tien
ts aged 2–19 years wi
th various in
tensely pre
trea
ted dissemina
ted brain
tumors received in
traven
tricular mafosfamide via an indwelling subcu
taneous reservoir. Twen
ty-
three of
them received a dose of 20&
thinsp;mg. Mafosfamide was adminis
tered once or
twice weekly un
til remission was achieved and every 2–6 weeks
thereaf
ter as main
tenance
therapy for a
to
tal of 736 adminis
tra
tions (2–63/pa
tien
t). Since March 1998,
two pa
tien
ts were swi
tched
to receive in
traven
tricular e
toposide and nine received e
toposide al
terna
ting wi
th mafosfamide. E
toposide was given a
t a dose of 0.5&
thinsp;mg&
times;5&
thinsp;d every 3–6 weeks for a
to
tal of 122 courses (1–29/pa
tien
t).
Immediate toxicities such as transient headaches, nausea, and vomiting occurred with mafosfamide but were manageable with premedication. Etoposide did not cause any discomfort. No long-term toxicities attributable to intrathecal therapy as evidenced by magnetic resonance imaging or neurologic evaluation were observed. Since all patients received some sort of concurrent anti-cancer therapy, the efficacy of intrathecal therapy cannot be assessed independently. However, seven of 13 patients evaluable for response by cerebrospinal fluid (CSF) cytology developed CSF dissemination under systemic chemotherapy and cleared their CSF only after administration of intrathecal mafosfamide. In conclusion, intraventricularly administered mafosfamide at a dose of 20 mg and etoposide at a dose of 0.5 mg×5 d for patients over 2 years of age are feasible and safe and may produce responses.