Temozolomide is an active agent in children with recurrent medulloblastoma/primitive neuroectodermal tumor: an Italian multi-institutional phase II trial.
BACKGROUND
The aim of this study was to assess the objective response rate (ORR) of children and young adults with recurrent medulloblastoma/primitive neuroectodermal tumor (MB/PNET) treated with temozolomide (TMZ). The secondary purpose was to analyze the toxicity profile of TMZ when administered orally for 5 days in 3 divided daily doses every 28 days.


METHODS
Forty-two patients with recurrent MB/PNET, aged 21 years and younger, were recruited. Patients were treated with oral TMZ. Starting doses ranged from 120 to 200 mg/m(2)/day based on previous treatments. A craniospinal MRI was performed prior to the first cycle of TMZ and following every 2 cycles of treatment.


RESULTS
Median age was 10 years (range, 2-21 years). Forty of 42 patients were assessed for response and toxicity. The objective response rate was 42.5%: 6 patients achieved a complete response, 11 had a partial response, and 10 had stable disease. Progression-free survival rates for all patients at 6 and 12 months were 30% and 7.5%, respectively. Their median overall survival rates at 6 and 12 months were 42.5% and 17.5%, respectively. No major extrahematological effects or life-threatening events were reported. The most common grade 3/4 toxicity included thrombocytopenia (17.5%), neutropenia (7.5%), and anemia (2.5%).


CONCLUSIONS
TMZ proved to be an effective agent in children and young adults with MB/PNET, heavily pre-treated, with a tolerable toxicity profile.
Pediatrics Unit, Fondazione IRCCS, Istituto Nazionale Tumori, Milan, Italy, (G.C., M.M., F.S.); Pediatric Oncology, A. Gemelli Hospital, Catholic University, Rome, Italy, (A.R., G.B., V.R., R.R.); Department of Radiodiagnostics, Fondazione IRCCS, Istituto Nazionale Tumori, Milan, Italy, (P.P.); Department of Chemotherapy, Istituto Ortopedico Rizzoli, Bologna, Italy, (M.E.A.); Department of Radiotherapy Unit, CRO, Aviano, Italy, (M.M.); Department of Neurosurgery, Ospedale G. Gaslini, Genova, Italy, (M.L.G.); Department of Pediatrics, University of Padua, Padua, Italy, (G.P.); Department of Pediatrics, Regina Margherita Children's Hospital, University of Turin, Turin, Italy, (E.M.); Department of Bioimaging and Radiological Sciences, Catholic University, Rome, Italy, (C.C.).
Graziella
G
Cefalo
Maura
M
Massimino
Antonio
A
Ruggiero
Giuseppe
G
Barone
Vita
V
Ridola
Filippo
F
Spreafico
Paolo
P
Potepan
Massimo E
ME
Abate
Maurizio
M
Mascarin
Maria Luisa
ML
Garrè
Giorgio
G
Perilongo
Enrico
E
Madon
Cesare
C
Colosimo
Riccardo
R
Riccardi
D000293:Adolescent; D000328:Adult; D018906:Antineoplastic Agents, Alkylating / Q000009:adverse effects / Q000627:therapeutic use*; D002528:Cerebellar Neoplasms / Q000188:drug therapy*; D002648:Child; D002675:Child, Preschool; D003606:Dacarbazine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007558:Italy; D008297:Male; D008527:Medulloblastoma / Q000188:drug therapy*; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy; D018242:Neuroectodermal Tumors, Primitive / Q000188:drug therapy*; D000077204:Temozolomide; D055815:Young Adult
D018906:Antineoplastic Agents, Alkylating; D003606:Dacarbazine; D000077204:Temozolomide
medulloblastoma; phase II trial; temozolomide