Synchronous radiochemotherapy in unfavorable brain tumors of children and young adults.
The prognosis of patients with incompletely resected malignant brain tumors is almost fatal. In an attempt to improve the outcome of children and young adults with unfavorable brain tumors an intensive multimodal therapeutic strategy was developed combining simultaneous (hyper)fractionated external beam irradiation and conventional adjuvant chemotherapy after initial surgery. 17 patients aged between 2.10 and 25.11 years were entered into the study. 16/17 patients were treated according to the German/Austrian Pediatric Brain Tumor Study Group multicenter trial HIT '91. They are not protocol patients of this HIT '91 trial. Induction chemotherapy consisted of 2 courses of ifosfamide (3 g/m2/d) on days 1-3, etoposide (150 mg/m2/d) on days 4-6, methotrexate (5 g/m2) on days 15 and 22, cisplatin (40 mg/m2/d) and cytarabine (400 mg/m2/d) on days 29-31. Three weeks after the last dose of cisplatin/cytarabine the second course of chemotherapy was started. The last patient entered into the study received a modified therapy containing ifosfamide, cisplatin and etoposide. Synchronously at a median of 12 days after initiation of chemotherapy 12/17 patients received local radiotherapy (6000-7040 cGy) to the brain and 5/17 patients craniospinal irradiation (3520 cGy with a tumor boost of 1400-2000 cGy). 4-6 weeks after completion of the second course of chemotherapy maintenance therapy was started with carmustine (CCNU) (75 mg/m2) and carboplatin (400 mg/m2) each on day 1 and vincristine (1.5 mg/m2) on day 1, 8, 15. This course was repeated eight times every six weeks. 9/17 patients are alive at a median follow-up of 25 months (range 5-50) with 4 complete remissions, 2 partial remissions and 1 stable disease lasting 42+ months. Two patients, who initially had stable disease, progressed, but are still alive at 31+ and 41+ months after diagnosis. Median progression-free survival and median overall survival is 19 and 36 months, respectively. Hematologic and methotrexate-induced toxicity were severe and resulted in one therapy-related death. However, radiotherapy concomitant to chemotherapy appears to be an effective method of treatment for brain tumors with poor prognosis, though toxicity is severe in some cases.
Division of Pediatric Hematology/Oncology, University Children's Hospital, University of Graz, Austria. christian.urban@kfunigraz.ac.at
C
C
Urban
M
M
Benesch
B
B
Pakisch
H
H
Lackner
R
R
Kerbl
W
W
Schwinger
R
R
Oberbauer
D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000188:drug therapy / Q000401:mortality / Q000532:radiotherapy / Q000601:surgery / Q000628:therapy*; D016190:Carboplatin / Q000008:administration & dosage; D056486:Chemical and Drug Induced Liver Injury; D017024:Chemotherapy, Adjuvant; D002648:Child; D002675:Child, Preschool; D002945:Cisplatin / Q000008:administration & dosage; D003131:Combined Modality Therapy; D016371:Cranial Irradiation; D003561:Cytarabine / Q000008:administration & dosage; D003638:Deafness / Q000139:chemically induced; D018450:Disease Progression; D018572:Disease-Free Survival; D005047:Etoposide / Q000008:administration & dosage; D005500:Follow-Up Studies; D005910:Glioma / Q000188:drug therapy / Q000401:mortality / Q000532:radiotherapy / Q000601:surgery; D034381:Hearing Loss / Q000139:chemically induced; D006402:Hematologic Diseases / Q000139:chemically induced; D006801:Humans; D007069:Ifosfamide / Q000008:administration & dosage; D007239:Infections / Q000209:etiology; D015993:Life Tables; D008130:Lomustine / Q000008:administration & dosage; D008527:Medulloblastoma / Q000188:drug therapy / Q000401:mortality / Q000532:radiotherapy / Q000601:surgery; D008727:Methotrexate / Q000008:administration & dosage / Q000009:adverse effects; D011379:Prognosis; D018714:Radiotherapy, Adjuvant; D012074:Remission Induction; D014750:Vincristine / Q000008:administration & dosage
D003561:Cytarabine; D014750:Vincristine; D005047:Etoposide; D008130:Lomustine; D016190:Carboplatin; D002945:Cisplatin; D007069:Ifosfamide; D008727:Methotrexate