Combination chemotherapy and radiotherapy for primary central nervous system lymphoma: Radiation Therapy Oncology Group Study 93-10.
OBJECTIVE
Primary CNS lymphoma (PCNSL) is an aggressive primary brain tumor. Cranial irradiation alone rarely results in long-term disease control or prolonged survival. We prospectively studied the use of combination chemotherapy plus cranial irradiation in newly diagnosed patients with PCNSL.


METHODS
We enrolled 102 newly diagnosed, immunocompetent patients with PCNSL; 98 were assessable. Patients first received five cycles of methotrexate 2.5 g/m(2), vincristine, procarbazine, and intraventricular methotrexate (12 mg). Whole-brain radiotherapy (RT) was administered to a total dose of 45 Gy and all patients received high-dose cytarabine after RT.


RESULTS
Fifty-eight percent of patients with measurable disease had a complete response to preirradiation chemotherapy and 36% had a partial (> 50%) response, for a 94% response rate. Median progression-free survival was 24.0 months and overall survival was 36.9 months. Age was an important prognostic factor; median survival was 50.4 months in patients younger than 60 and only 21.8 months in those aged 60 or older (P <.001). Fifty-three percent of patients had grade 3 or 4 toxicity during induction chemotherapy, half of which was hematologic. However, 12 patients (15%) experienced severe delayed neurologic toxicity, eight of whom died.


CONCLUSIONS
This is the first multicenter trial demonstrating improved survival with the combination of chemotherapy plus RT compared with previous reports of RT alone. A high-dose methotrexate-based regimen produced a high response rate before RT was administered. High-dose methotrexate combined with cranial irradiation is an effective therapeutic approach to PCNSL, but neurotoxicity is a delayed risk of this approach.
DeAngelis
Lisa M
LM
Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA. deangell@mskcc.org
Seiferheld
Wendy
W
Schold
S Clifford
SC
Fisher
Barbara
B
Schultz
Christopher J
CJ
D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage; D000970:Antineoplastic Agents / Q000008:administration & dosage; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols; D001932:Brain Neoplasms / Q000401:mortality / Q000532:radiotherapy / Q000628:therapy*; D003131:Combined Modality Therapy; D003561:Cytarabine / Q000008:administration & dosage; D006801:Humans; D008223:Lymphoma / Q000401:mortality / Q000532:radiotherapy / Q000628:therapy*; D008727:Methotrexate / Q000008:administration & dosage; D011344:Procarbazine / Q000008:administration & dosage; D015996:Survival Rate; D014750:Vincristine / Q000008:administration & dosage
D000964:Antimetabolites, Antineoplastic; D000970:Antineoplastic Agents; D000972:Antineoplastic Agents, Phytogenic; D003561:Cytarabine; D011344:Procarbazine; D014750:Vincristine; D008727:Methotrexate