A medical research council randomized trial in patients with primary cerebral non-Hodgkin lymphoma: cerebral radiotherapy with and without cyclophosphamide, doxorubicin, vincristine, and prednisone chemotherapy.
BACKGROUND
The role of chemotherapy in the treatment of patients with primary central nervous system lymphoma (PCL) remains unclear, with no randomized trials available to aid in the interpretation of the current data. The Medical Research Council therefore conducted the current randomized trial to assess the impact on survival of postradiotherapy chemotherapy with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) in nonimmunocompromised adult patients with pathologically proven PCL.


METHODS
After surgery, patients were randomized at a ratio of 1:2 to radiotherapy alone (RT: 40 grays [Gy] in 20 fractions to the whole brain followed by a 14-Gy boost to the tumor plus a 2-cm tumor margin) or to the same radiotherapy followed by six cycles of CHOP chemotherapy given at 3-week intervals (RT-CHOP). The target sample size was 90 patients, which allowed 90% power to detect a doubling of the median survival time.


RESULTS
Between 1988 and 1995, 53 patients were randomized: Fifteen patients were randomized to RT, and 38 patients were randomized to RT-CHOP. The trial closed earlier than planned through poor accrual. The median patient age was 57 years, 57% of the patients were male, and 75% of the patients had unifocal disease. The median number of chemotherapy cycles received was 6 (mean, 4 cycles). Forty-three patients have died, and the median follow-up of survivors is 5 years (range, 1-9 years). There was no evidence of a benefit from RT-CHOP with respect to overall survival (hazard ratio [HR], 1.19; 95% confidence interval, 0.51-2.76) after adjustment for prognostic factors (patient age and neurologic performance status) in an analysis in which HR > 1 favored the control (RT) group.


CONCLUSIONS
CHOP has no clear role in the postradiotherapy treatment of patients with PCL. Chemotherapy is poorly tolerated and largely palliative in older, less fit patients. In younger patients, initial chemotherapy designed to penetrate the blood-brain barrier warrants further investigation.
Mead
G M
GM
Royal South Hants Hospital, Southampton, United Kingdom.
Bleehen
N M
NM
Gregor
A
A
Bullimore
J
J
Shirley
D
D
Rampling
R P
RP
Trevor
J
J
Glaser
M G
MG
Lantos
P
P
Ironside
J W
JW
Moss
T H
TH
Brada
M
M
Whaley
J B
JB
Stenning
S P
SP
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy*; D017024:Chemotherapy, Adjuvant; D016371:Cranial Irradiation; D003520:Cyclophosphamide / Q000008:administration & dosage; D018572:Disease-Free Survival; D004317:Doxorubicin / Q000008:administration & dosage; D005260:Female; D006801:Humans; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy* / Q000532:radiotherapy*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011241:Prednisone / Q000008:administration & dosage; D016019:Survival Analysis; D014750:Vincristine / Q000008:administration & dosage
D014750:Vincristine; D004317:Doxorubicin; D003520:Cyclophosphamide; D011241:Prednisone