High-dose methotrexate-based chemotherapy followed by consolidating radiotherapy in non-AIDS-related primary central nervous system lymphoma: European Organization for Research and Treatment of Cancer Lymphoma Group Phase II Trial 20962.
OBJECTIVE
To confirm the feasibility and estimate the efficacy of methotrexate (MTX), teniposide, carmustine, and methylprednisolone (MBVP) chemotherapy combined with radiotherapy (RT) for patients with non-AIDS-related primary CNS lymphoma (PCNSL) treated in a multicenter setting.


METHODS
Treatment consisted of two cycles of MBVP (MTX 3 g/m2 days 1 and 15, teniposide 100 mg/m2 days 2 and 3, carmustine 100 mg/m2 day 4, methylprednisolone 60 mg/m2 days 1 to 5, and two intrathecal injections of MTX 15 mg, cytarabine 40 mg, and hydrocortisone 25 mg) followed by 40 Gy of RT. Primary end points were response and safety of this regimen.


RESULTS
Twelve centers included 52 patients who were all analyzed on an intent-to-treat basis. Median follow-up of all patients was 27 months. One patient progressed and died before treatment, and five patients died during treatment. Four patients received RT after one cycle of chemotherapy, and 42 patients completed the entire treatment. Hematologic grade 3 and 4 toxicity was seen in 78% of patients for leukocytes and 24% of patients for platelets. The overall response rate of all 52 patients was 81%. Two patients who did not fulfill the criteria of objective response survived more than 1 year; one of them is still alive without disease. Eighteen patients died; 11 deaths were a result of tumor, five were probably treatment-related, one was caused by late leukoencephalopathy, and one was a result of intercurrent disease. Median estimated overall survival was 46 months.


CONCLUSIONS
MBVP followed by RT for PCNSL has a high response rate. However, the 10% toxic death rate during treatment in a multicenter setting underlines the need for highly specialized care.
Poortmans
Philip M P
PM
Dr Bernard Verbeeten Instituut, PO Box 90120, 5000 LA Tilburg, The Netherlands. poortmans.ph@bvi.nl
Kluin-Nelemans
Hanneke C
HC
Haaxma-Reiche
Hanny
H
Van't Veer
Mars
M
Hansen
Mads
M
Soubeyran
Pierre
P
Taphoorn
Martin
M
Thomas
José
J
Van den Bent
Martin
M
Fickers
Martin
M
Van Imhoff
Gustaaf
G
Rozewicz
Cynthia
C
Teodorovic
Ivana
I
van Glabbeke
Martine
M
D000293:Adolescent; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002330:Carmustine / Q000008:administration & dosage; D016543:Central Nervous System Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*; D003131:Combined Modality Therapy; D005260:Female; D006801:Humans; D008223:Lymphoma / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage; D008775:Methylprednisolone / Q000008:administration & dosage; D008875:Middle Aged; D011446:Prospective Studies; D016019:Survival Analysis; D013713:Teniposide / Q000008:administration & dosage; D016896:Treatment Outcome
D013713:Teniposide; D002330:Carmustine; D008775:Methylprednisolone; D008727:Methotrexate