Immunochemotherapy with rituximab and temozolomide for central nervous system lymphomas.
BACKGROUND
Methotrexate-based and alkylator-based chemotherapy regimens are associated with renal and bone marrow toxicities, which limit their use in patients with central nervous system (CNS) lymphomas. The authors report their experience with an immunochemotherapy regimen consisting of rituximab and temozolomide in patients with primary or metastatic CNS lymphoma.


METHODS
Seven patients who had received rituximab and temozolomide were identified from the database of the brain tumor clinic at the authors' institution: three patients had developed recurrent primary CNS lymphoma (PCNSL), one patient had newly diagnosed PCNSL but had poor renal function, and three other patients with systemic non-Hodgkin lymphoma developed recurrent lymphoma in the brain only. Patients were scheduled to receive 4 cycles of induction rituximab on Day 1 and temozolomide on Days 1-5 of a 28-day cycle. Thereafter, their treatment included a total of up to 8 maintenance cycles of temozolomide alone on Days 1-5 of a 28-day cycle. A gadolinium-enhanced magnetic resonance image of the head was obtained after every two cycles of treatment.


RESULTS
All patients received rituximab without toxicity. Of the 4 patients who received induction temozolomide at doses > 150 mg/m(2) daily on Days 1-5, 2 experienced Grade 2 leukopenia and thrombocytopenia. Five patients achieved a radiographic complete response, and two patients had partial responses after induction treatment. The median response duration was 6 months (range 3-12+ months), and the median survival was 8 months (range 3+-12+ months).


CONCLUSIONS
Although median survival was short, immunochemotherapy with rituximab and temozolomide was well tolerated and exhibited efficacy in this elderly and heavily pretreated cohort. The data obtained in the current study suggest that the optimal induction dose combination consists of rituximab 375 mg/m(2) on Day 1 and temozolomide 150 mg/m(2) daily on Days 1-5.
Wong
Eric T
ET
Brain Tumor Center and Neuro-Oncology Unit, Harvard Medical School/Beth Israel Deaconess Medical Center, 330 Brookline Avenue, Boston, MA 02215, USA. ewong@bidmc.harvard.edu
Tishler
Roy
R
Barron
Loretta
L
Wu
Julian K
JK
D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects; D058846:Antibodies, Monoclonal, Murine-Derived; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D016543:Central Nervous System Neoplasms / Q000188:drug therapy* / Q000401:mortality; D003606:Dacarbazine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D004357:Drug Synergism; D006801:Humans; D008223:Lymphoma / Q000188:drug therapy* / Q000401:mortality; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D000069283:Rituximab; D000077204:Temozolomide; D016896:Treatment Outcome
D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D000069283:Rituximab; D003606:Dacarbazine; D000077204:Temozolomide