Radiation therapy and bromodeoxyuridine chemotherapy followed by procarbazine, lomustine, and vincristine for the treatment of anaplastic gliomas.
OBJECTIVE
To conduct a Phase II study to evaluate the long-term efficacy and safety of radiotherapy combined with intravenous bromodeoxyuridine for patients with anaplastic glioma tumors.


METHODS
Between 1983 and 1987, study patients received 1.7-1.8 Gy radiation once a day, Monday through Friday, to a total dose of 60 Gy. On the Thursday prior to beginning radiotherapy and for the next 5 weeks (6 weeks total), patients received a continuous 96 h intravenous infusion of bromodeoxyuridine at 0.8 g/m2/24 h; following radiotherapy, patients received procarbazine, lomustine (CCNU), and vincristine (PCV) for 1 year or until tumor progressed.


RESULTS
One-hundred thirty eight patients (median age, 43 years) were evaluable for analysis. Estimated 4-year survival for the anaplastic astrocytoma (AA) stratum (n = 116) is 46%. For the astrocytoma (ASTRO) stratum (n = 22), the 6-year survival is estimated at 79%. Estimated 4-year progression-free survival for AAs is 42%, and for ASTROs, 68%. Whole brain irradiation was used in 23% and limited-field irradiation in 77%; patients receiving limited-field irradiation had a better survival rate (p = 0.07). Total tumor resection was performed in 15%, partial resection in 53%, and biopsy only in 32%. For the 81 patients with tumor recurrence, 34 (42%) are known to have received additional treatment(s). For AA, fits of the Cox proportional hazards regression model showed that covariates individually predictive of survival were younger age (p < 0.001), Karnofsky performance score (p = 0.10). Major toxicities were rash during Weeks 1 through 6 requiring dose modification in 14%, Grade > or = III leukopenia in 18%, and Grade > or = III thrombocytopeni in 9%.


CONCLUSIONS
The study suggests that the bromodeoxyuridine-radiotherapy-PCV, compared with other published therapies, can improve progression-free survival, and aggressive treatment of ASTRO patients can lead to substantial increases in survival compared to published survival data.
Levin
V A
VA
Northern California Cancer Center, Union City, USA.
Prados
M R
MR
Wara
W M
WM
Davis
R L
RL
Gutin
P H
PH
Phillips
T L
TL
Lamborn
K
K
Wilson
C B
CB
D000293:Adolescent; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001254:Astrocytoma / Q000188:drug therapy* / Q000401:mortality / Q000532:radiotherapy*; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000532:radiotherapy*; D001973:Bromodeoxyuridine / Q000008:administration & dosage* / Q000009:adverse effects; D003131:Combined Modality Therapy; D018572:Disease-Free Survival; D005909:Glioblastoma / Q000188:drug therapy* / Q000401:mortality / Q000532:radiotherapy*; D006801:Humans; D008130:Lomustine / Q000008:administration & dosage; D008875:Middle Aged; D011344:Procarbazine / Q000008:administration & dosage; D014750:Vincristine / Q000008:administration & dosage
D011344:Procarbazine; D014750:Vincristine; D008130:Lomustine; D001973:Bromodeoxyuridine