A lower-dose, lower-toxicity cisplatin-etoposide regimen for childhood progressive low-grade glioma.
After successfully using cisplatin (30 mg/m(2)/day) and etoposide (150 mg/m(2)/day) in ten three-day courses for progressive low-grade gliomas, a subsequent protocol reduced the daily doses of cisplatin (to 25 mg) and etoposide (to 100 mg), with the objective of achieving the same response and three-year PFS rates with lower neurotoxicity and myelotoxicity. We treated 37 patients (median age 6 years); 23 had optochiasmatic tumours and nine were metastatic cases. Diagnoses were clinical in 13 cases and histological in 24, and comprised: pilocytic astrocytoma (17), ganglioglioma (3), pilomyxoid astrocytoma (2), and fibrillary astrocytoma (2). Treatment was prompted by radiological evidence of progression and/or clinical deterioration a median 18 months after the first diagnosis. After initial MRI staging, neurological and clinical examinations were performed before each chemotherapy cycle, with MRI after the first three courses and every three months thereafter. After a median 48 months, a volume reduction was appreciable in 24 cases (65%) and response was maximum 12 months after starting treatment. The three-year EFS and OS rates were 65 and 97%, respectively. Clinical, neurological, or functional improvements were seen in 26/37 cases. No children had a WBC nadir below 2,000/mm(3). Audiological toxicity caused damage in 4/34 cases. The previous protocol had achieved volume reductions in 70% of cases, causing audiological damage (data updated) in 11/31 (P = 0.023), with three-year PFS and OS rates of 70 and 100%, respectively. Lower doses of cisplatin/etoposide are still effective in progressive low-grade glioma, with less acute and persistent morbidity.
Division of Paediatrics, Fond. IRCCS Istituto Nazionale Tumori, Via Venezian 1, 20133, Milan, Italy. maura.massimino@istitutotumori.mi.it
Maura
M
Massimino
Filippo
F
Spreafico
Daria
D
Riva
Veronica
V
Biassoni
Geraldina
G
Poggi
Carlo
C
Solero
Lorenza
L
Gandola
Lorenzo
L
Genitori
Piergiorgio
P
Modena
Fabio
F
Simonetti
Paolo
P
Potepan
Michela
M
Casanova
Cristina
C
Meazza
Carlo A
CA
Clerici
Serena
S
Catania
Iacopo
I
Sardi
Felice
F
Giangaspero
D000293:Adolescent; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols; D001932:Brain Neoplasms / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality; D002648:Child; D002675:Child, Preschool; D002945:Cisplatin / Q000627:therapeutic use*; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D004569:Electroencephalography; D005047:Etoposide / Q000627:therapeutic use*; D005074:Evoked Potentials, Visual / Q000187:drug effects; D005260:Female; D005910:Glioma / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male
D000970:Antineoplastic Agents; D005047:Etoposide; D002945:Cisplatin