Combined immunochemotherapy with reduced whole-brain radiotherapy for newly diagnosed primary CNS lymphoma Journal Article


Authors: Shah, G. D.; Yahalom, J.; Correa, D. D.; Lai, R. K.; Raizer, J. J.; Schiff, D.; LaRocca, R.; Grant, B.; Deangelis, L. M.; Abrey, L. E.
Article Title: Combined immunochemotherapy with reduced whole-brain radiotherapy for newly diagnosed primary CNS lymphoma
Abstract: Purpose: Our goals were to evaluate the safety of adding rituximab to methotrexate (MTX)-based chemotherapy for primary CNS lymphoma, determine whether additional cycles of induction chemotherapy improve the complete response (CR) rate, and examine effectiveness and toxicity of reduced-dose whole-brain radiotherapy (WBRT) after CR. Patients and Methods: Thirty patients (17 women; median age, 57 years; median Karnofsky performance score, 70) were treated with five to seven cycles of induction chemotherapy (rituximab, MTX, procarbazine, and vincristine [R-MPV]) as follows: day 1, rituximab 500 mg/m2; day 2, MTX 3.5 gm/m2 and vincristine 1.4 mg/m 2. Procarbazine 100 mg/m2/d was administered for 7 days with odd-numbered cycles. Patients achieving CR received dose-reduced WBRT (23.4 Gy), and all others received standard WBRT (45 Gy). Two cycles of high-dose cytarabine were administered after WBRT. CSF levels of rituximab were assessed in selected patients, and prospective neurocognitive evaluations were performed. Results: With a median follow-up of 37 months, 2-year overall and progression-free survival was 67% and 57%, respectively. Forty-four percent of patients achieved a CR after five or fewer cycles, and 78% after seven cycles. The overall response rate was 93%. Nineteen of 21 CR patients received the planned 23.4 Gy WBRT. The most commonly observed grade 3 to 4 toxicities included neutropenia (43%), thrombocytopenia (36%), and leukopenia (23%). No treatment-related neurotoxicity has been observed. Conclusion: The addition of rituximab to MPV increased the risk of significant neutropenia requiring routine growth factor support. Additional cycles of R-MPV nearly doubled the CR rate. Reduced-dose WBRT was not associated with neurocognitive decline, and disease control to date is excellent. © 2007 by American Society of Clinical Oncology.
Keywords: adult; cancer chemotherapy; clinical article; controlled study; treatment outcome; treatment response; aged; middle aged; clinical trial; neutropenia; drug safety; drug withdrawal; multimodality cancer therapy; disease free survival; combined modality therapy; cytarabine; methotrexate; rituximab; drug megadose; neurotoxicity; outcome assessment; follow up; antineoplastic agent; prospective study; prospective studies; cancer immunotherapy; multiple cycle treatment; anemia; leukopenia; thrombocytopenia; antineoplastic combined chemotherapy protocols; clinical assessment; vincristine; procarbazine; central nervous system tumor; skull irradiation; cranial irradiation; central nervous system neoplasms; monoclonal antibody; febrile neutropenia; lymphocytopenia; standard; acute kidney failure; immunology; antibodies, monoclonal; karnofsky performance status; immunotherapy; multicenter study; folinic acid; lymphoma; remission; remission induction; cognition; recombinant granulocyte colony stimulating factor; brain lymphoma; septic shock; drug brain level; cerebrospinal fluid level
Journal Title: Journal of Clinical Oncology
Volume: 25
Issue: 30
ISSN: 0732-183X
Publisher: American Society of Clinical Oncology  
Date Published: 2007-10-20
Start Page: 4730
End Page: 4735
Language: English
DOI: 10.1200/jco.2007.12.5062
PUBMED: 17947720
PROVIDER: scopus
DOI/URL:
Notes: --- - "Cited By (since 1996): 61" - "Export Date: 17 November 2011" - "CODEN: JCOND" - "Source: Scopus"
Altmetric Score
MSK Authors
  1. Joachim Yahalom
    394 Yahalom
  2. Denise D Correa
    65 Correa
  3. Jeffrey J Raizer
    21 Raizer
  4. Gaurav D Shah
    12 Shah
  5. Lauren E Abrey
    272 Abrey