Treatment > Chemoresistance · Temozolomide Clinical Trials  

Meeting Abstract

Phase II treatment of adults with newly diagnosed, progressive or recurrent primary central nervous system lymphoma with temozolomide

B. Evans, J. Quinn, D. Reardon, J. Rich, S. Gururangan, A. Friedman, R. McLendon, S. Tourt-Uhlig, V. Stafford-Fox, H. S. Friedman

Duke Medical Center, Durham, NC; Schering Oncology Biotech, Kenilworth, NJ

We are conducting a phase II trial to define the activity and toxicity of temozolomide (Temodar) (T) in the treatment of adults with newly diagnosed and progressive or recurrent PCNSL.
One obstacle to T cytotoxicity is the DNA repair enzyme O⁶-alkylguanine-DNA alkyltransferase (AGT).
AGT removes from O⁶-guanine the methyl groups that would otherwise lead to apoptotic cell death.
In several laboratory studies resistance to T correlates with high AGT levels whereas sensitivity to T correlates with low AGT levels.
Therefore, we are also characterizing the relationship between AGT levels and response to T.
Patients are being treated with T orally for the first 5 days of a 28-day cycle at a dose of 200 mg/m²/day.
A combination of T₁-weighted enhanced MRI images and CSF analysis are being utilized to evaluate response.
Immunochemistry with monoclonal antibodies was used to detect the percentage of tumor cells staining positive for AGT.
Eight patients have been treated to date, 5 with newly diagnosed disease and 3 with recurrent disease.
Two patients, 1 with newly diagnosed disease and 1 with recurrent disease, have shown a complete response and are disease free 22 and 20 months after starting T, respectively.
Five patients have shown disease progression after 1 cycle and 1 patient progressed after 2 cycles.
No >= grade 3 toxicities have been seen thus far.
AGT reactivity was obtained on all but one patient.
One hundred percent of the tumor cells stained positive for AGT in 5 of 7 (71%) patients all of whom progressed within 1-2 cycles of receiving T.
Twenty-five percent or fewer of the tumor cells stained positive for AGT in 2 of 7 (29%) patients all of whom responded completely to T.
Further enrollment into this phase II protocol will continue.

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