Chemoradiotherapy for primary CNS lymphoma: an intent-to-treat analysis with complete follow-up.
OBJECTIVE
To assess the efficacy and safety of a preradiation chemotherapy regimen in patients with primary CNS lymphoma (PCNSL), with emphasis on long-term outcomes.


METHODS
In this prospective phase II trial, patients with a new diagnosis of PCNSL received two cycles of intrathecal (12 mg) and IV (1 g/m2) methotrexate (MTX), thiotepa (30 mg/m2), and procarbazine (75 mg/m2), prior to whole-brain radiotherapy (RT).


RESULTS
Seventeen patients were enrolled (ages 26 to 71, median 53). Median Karnofsky performance scale score was 70. After chemotherapy, 7 patients (41%) had a complete response (CR) and 7 (41%) a partial response (PR). After RT, 13 (76%) patients achieved a CR, 2 (12%) a PR, and 2 (12%) had disease progression. Relapse occurred in 7 (41%) patients; median disease-free survival was 18 months. Fifteen (88%) patients have died: 8 (47%) from PCNSL, 5 (29%) from neurotoxicity, and 2 (12%) from unknown causes. Median overall survival was 32 months. Two patients (12%) are alive and disease free at 12 years follow-up. Nephrotoxicity was a minor complication, but grades 3 and 4 myelosuppression were found in 5 (29%) patients.


CONCLUSIONS
This regimen resulted in an efficacy and toxicity profile comparable to other combined modality treatments, despite the relatively low dose of methotrexate. It may be a useful option in patients unable to tolerate higher doses. Procarbazine and thiotepa are potential candidates for incorporation into chemotherapy regimens aiming to decrease the incidence of neurotoxicity. First relapse and neurotoxicity within 2 years of diagnosis seem to be critical for predicting long-term outcomes.
Omuro
Antonio M P
AM
Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
DeAngelis
Lisa M
LM
Yahalom
Joachim
J
Abrey
Lauren E
LE
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use; D001921:Brain / Q000187:drug effects / Q000528:radiation effects; D016543:Central Nervous System Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy; D003131:Combined Modality Therapy / Q000009:adverse effects / Q000379:methods; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007278:Injections, Spinal; D008223:Lymphoma / Q000188:drug therapy* / Q000532:radiotherapy; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage / Q000627:therapeutic use; D008875:Middle Aged; D011344:Procarbazine / Q000008:administration & dosage / Q000627:therapeutic use; D011446:Prospective Studies; D015996:Survival Rate; D013852:Thiotepa / Q000008:administration & dosage / Q000627:therapeutic use; D016896:Treatment Outcome
D011344:Procarbazine; D013852:Thiotepa; D008727:Methotrexate