No salvage using high-dose chemotherapy plus/minus reirradiation for relapsing previously irradiated medulloblastoma.
OBJECTIVE
Myeloablative regimens were frequently used for medulloblastoma relapsing after craniospinal irradiation (CSI): in 1997-2002, we used repeated surgery, standard-dose and myeloablative chemotherapy, and reirradiation.


METHODS
In 10 patients, reinduction included sequential high-dose etoposide, high-dose cyclophosphamide/vincristine, and high-dose carboplatin/vincristine, then two myeloablative courses with high-dose thiotepa (+/- carboplatin); 6 other patients received two of four courses of cisplatin/etoposide. Hematopoietic precursor mobilization followed high-dose etoposide or high-dose cyclophosphamide or cisplatin/etoposide therapy. After the overall chemotherapy program, reirradiation was prescribed when possible.


RESULTS
Seventeen patients were treated: previous treatment included CSI of 19.5-36 Gy with posterior fossa/tumor boost and chemotherapy in 16 patients. Fifteen patients were in their first and 2 in their second and third relapses, respectively. First progression-free survival had lasted a median of 26 months. Relapse sites included leptomeninges in 9 patients, spine in 4 patients, posterior fossa in 3 patients, and brain in 1 patient. Three patients underwent complete resection of recurrence, and 10 underwent reirradiation. Twelve of 14 patients with assessable tumor had an objective response after reinduction; 2 experienced progression and were not given the myeloablative courses. Remission lasted a median of 16 months. Additional relapses appeared in 13 patients continuing the treatment. Fifteen patients died of progression and 1 died of pneumonia 13 months after relapse. The only survivor at 93 months had a single spinal metastasis that was excised and irradiated. Survival for the series as a whole was 11-93 months, with a median of 41 months.


CONCLUSIONS
Despite responses being obtained and ample use of surgery and reirradiation, second-line therapy with myeloablative schedules was not curative, barring a few exceptions. A salvage therapy for medulloblastoma after CSI still needs to be sought.
Massimino
Maura
M
Division of Pediatrics, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy. maura.massimino@istitutotumori.mi.it
Gandola
Lorenza
L
Spreafico
Filippo
F
Biassoni
Veronica
V
Luksch
Roberto
R
Collini
Paola
P
Solero
Carlo N
CN
Simonetti
Fabio
F
Pignoli
Emanuele
E
Cefalo
Graziella
G
Poggi
Geraldina
G
Modena
Piergiorgio
P
Mariani
Luigi
L
Potepan
Paolo
P
Podda
Marta
M
Casanova
Michela
M
Pecori
Emilia
E
Acerno
Stefania
S
Ferrari
Andrea
A
Terenziani
Monica
M
Meazza
Cristina
C
Polastri
Daniela
D
Ravagnani
Fernando
F
Fossati-Bellani
Franca
F
D000293:Adolescent; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage / Q000009:adverse effects; D002528:Cerebellar Neoplasms / Q000188:drug therapy / Q000401:mortality / Q000532:radiotherapy / Q000601:surgery; D002648:Child; D002675:Child, Preschool; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects; D003131:Combined Modality Therapy / Q000379:methods; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D005047:Etoposide / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage; D006801:Humans; D008297:Male; D008527:Medulloblastoma / Q000188:drug therapy / Q000401:mortality / Q000532:radiotherapy / Q000601:surgery; D008727:Methotrexate / Q000008:administration & dosage / Q000009:adverse effects; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy / Q000401:mortality / Q000532:radiotherapy / Q000601:surgery; D011879:Radiotherapy Dosage; D012074:Remission Induction / Q000379:methods; D016879:Salvage Therapy; D013852:Thiotepa / Q000008:administration & dosage / Q000009:adverse effects; D014750:Vincristine / Q000008:administration & dosage / Q000009:adverse effects; D055815:Young Adult
D016179:Granulocyte Colony-Stimulating Factor; D014750:Vincristine; D005047:Etoposide; D003520:Cyclophosphamide; D013852:Thiotepa; D016190:Carboplatin; D002945:Cisplatin; D008727:Methotrexate