Feasibility of long-term intraventricular therapy with mafosfamide (n = 26) and etoposide (n = 11): experience in 26 children with disseminated malignant brain tumors.
Treatment options for leptomeningeal disseminated brain tumors are limited by the lack of effective drugs for intrathecal therapy of non-hematologic malignancies. We report on our experience with an intraventricular therapy consisting of mafosfamide, a preactivated cyclophosphamide derivative, and etoposide. Between May 1994 and 2002, 26 patients aged 2-19 years with various intensely pretreated disseminated brain tumors received intraventricular mafosfamide via an indwelling subcutaneous reservoir. Twenty-three of them received a dose of 20 mg. Mafosfamide was administered once or twice weekly until remission was achieved and every 2-6 weeks thereafter as maintenance therapy for a total of 736 administrations (2-63/patient). Since March 1998, two patients were switched to receive intraventricular etoposide and nine received etoposide alternating with mafosfamide. Etoposide was given at a dose of 0.5 mg x 5 d every 3-6 weeks for a total of 122 courses (1-29/patient). 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 x 5 d for patients over 2 years of age are feasible and safe and may produce responses.
Slavc
Irene
I
Department of Pediatrics, University of Vienna, Vienna, Austria. irene.slave@akh-wien.ac.at
Schuller
Elisabeth
E
Falger
Jutta
J
Günes
Mehmet
M
Pillwein
Konrad
K
Czech
Thomas
T
Dietrich
Wolfgang
W
Rössler
Karl
K
Dieckmann
Karin
K
Prayer
Daniela
D
Hainfellner
Johannes
J
D000293:Adolescent; D000328:Adult; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000134:cerebrospinal fluid; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D001932:Brain Neoplasms / Q000134:cerebrospinal fluid / Q000188:drug therapy* / Q000556:secondary; D002648:Child; D002675:Child, Preschool; D003520:Cyclophosphamide / Q000008:administration & dosage* / Q000031:analogs & derivatives*; D005047:Etoposide / Q000008:administration & dosage*; D005240:Feasibility Studies; D005260:Female; D005500:Follow-Up Studies; D006261:Headache / Q000139:chemically induced; D006801:Humans; D007276:Injections, Intraventricular; D007278:Injections, Spinal; D008297:Male; D008577:Meningeal Neoplasms / Q000134:cerebrospinal fluid / Q000188:drug therapy / Q000473:pathology; D009325:Nausea / Q000139:chemically induced; D010146:Pain / Q000139:chemically induced; D016896:Treatment Outcome
D000970:Antineoplastic Agents; C048341:mafosfamide; D005047:Etoposide; D003520:Cyclophosphamide