Concurrent accelerated hyperfractionated radiation therapy and carboplatin/etoposide in patients with malignant glioma: long-term results of a phase II study.
OBJECTIVE
Feasibility, antitumor activity and toxicity of accelerated hyperfractionated radiation therapy (Acc Hfx RT) and concurrent carboplatin/etoposide (CBDCA/VP 16) chemotherapy were investigated in patients with malignant glioma.


METHODS
Seventy-nine patients with either glioblastoma multiforme (GBM) (n = 61) or anaplastic astrocytome (AA) (n = 18) entered into a phase II study on the use of Acc Hfx RT with 60 Gy in 40 fractions in 20 treatment days over 4 weeks and concurrent CBDCA, 200 mg/m2, and VP 16, 200 mg/m2, both given once weekly during the RT course.


RESULTS
The median survival time for all 79 patients was 14 months (11 and 44 months for GBM and AA patients, respectively), while the 2- and 4-year survival was respectively 33% and 11% for all patients, 13% and 1.6% for GBM patients, and 100% and 44% for AA patients (p < 0.0001). The median time to progression for all patients was 12 months (9 and 40 months for GBM and AA, respectively), while the 2- and 4-year progression-free survival (PFS) was respectively 28% and 10% (all patients), 10% and 1.7% (GBM) and 89% and 39% (AA) (p < 0.0001). Multivariate analysis showed that age, performance status, and preoperative size of tumor influenced survival in GBM. Only 5 (6%) patients experienced grade 3 leukopenia and 6 (8%) patients experienced grade 3 thrombocytopenia. No late RT-induced toxicity was observed to date.


CONCLUSIONS
Although Acc Hfx RT/CBDCA + VP 16 was feasible and little toxic, it failed to improve survival/progression-free survival over that obtained with other currently used regimens. These results do not justify the investigation of this regimen in a phase III trial.
Jeremic
B
B
Department of Oncology, University Hospital, Kragujevac, Yugoslavia. bjeremic@meo.uni-tuebingen.de
Shibamoto
Y
Y
Grujicic
D
D
Stojanovic
M
M
Milicic
B
B
Nikolic
N
N
Dagovic
A
A
Aleksandrovic
J
J
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001254:Astrocytoma / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy*; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy*; D016190:Carboplatin / Q000008:administration & dosage; D003131:Combined Modality Therapy; D019583:Dose Fractionation, Radiation; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D005500:Follow-Up Studies; D005909:Glioblastoma / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011878:Radiotherapy / Q000009:adverse effects; D015996:Survival Rate; D013997:Time Factors
D005047:Etoposide; D016190:Carboplatin