Phase II trial of chemotherapy alone for primary CNS and intraocular lymphoma.
OBJECTIVE
Primary CNS lymphoma (PCNSL) and primary intraocular lymphoma (IOL) are usually treated with radiation therapy alone or in combination with chemotherapy. The neurotoxicity of these treatments can be substantial. This study attempts to define the toxicity and efficacy of the treatment of this disease with chemotherapy alone.


METHODS
Fourteen nonimmunocompromised patients were accrued to a chemotherapy regimen that incorporated a 24-hour infusion of high-dose methotrexate total dose of 8.4 g/m2 with leucovorin rescue; thiotepa 35 mg/m2; vincristine 1.4 mg/m2; dexamethasone; and intrathecal cytarabine (Ara-C) and methotrexate (MTV) administered in 21-day cycles. Seven patients were prospectively followed up with formal neuropsychologic assessments for evidence of CNS toxicity.


RESULTS
The response rate was 100% with 11 (79%) complete responses and three (21%) partial responses. Cumulative survival and progression-free survival rates at more than 4.5 years were 68.8% and 34.3%, respectively. Median survival has not been reached, and median progression-free survival was 16.5 months. Toxicity included severe leukoencephalopathy that was clearly attributable to chemotherapy (two patients), grade 3 or 4 neutropenia in 50% of the cycles administered, ileus (one patient), and seizures (two patients). Mucositis and renal and hepatic toxicity were mild and not therapy limiting.


CONCLUSIONS
The MTV regimen is generally well tolerated and produces a high complete response rate. Chemotherapy alone should be investigated further in this disease to assess the necessity of initial radiation therapy, either alone or in combined modality regimens, for the achievement of optimal response and survival.
Sandor
V
V
Medicine and Pediatric Branches, Department of Neurosurgery, Division of Cancer Treatment and Diagnosis, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-2440, USA.
Stark-Vancs
V
V
Pearson
D
D
Nussenblat
R
R
Whitcup
S M
SM
Brouwers
P
P
Patronas
N
N
Heiss
J
J
Jaffe
E
E
deSmet
M
M
Kohler
D
D
Simon
R
R
Wittes
R
R
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D016543:Central Nervous System Neoplasms / Q000188:drug therapy*; D003561:Cytarabine / Q000008:administration & dosage; D003907:Dexamethasone / Q000008:administration & dosage; D004334:Drug Administration Schedule; D005134:Eye Neoplasms / Q000188:drug therapy*; D005260:Female; D006801:Humans; D002955:Leucovorin / Q000008:administration & dosage; D016393:Lymphoma, B-Cell / Q000188:drug therapy*; D016403:Lymphoma, Large B-Cell, Diffuse / Q000188:drug therapy*; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage; D008875:Middle Aged; D010865:Pilot Projects; D013852:Thiotepa / Q000008:administration & dosage; D014750:Vincristine / Q000008:administration & dosage
D003561:Cytarabine; D014750:Vincristine; D003907:Dexamethasone; D013852:Thiotepa; D002955:Leucovorin; D008727:Methotrexate