Idarubicin combined with high dose methotrexate and moderate dose radiotherapy will achieve similar survival outcomes but with reduced neurotoxicity compared to regimens using methotrexate with high dose radiotherapy.

Combined modality therapy in PCNSL has improved survival outcomes but at the cost of unacceptable rates of neurotoxicity when high dose radiotherapy is used. Idarubicin has activity in systemic lymphomas and crosses the blood brain barrier and may add to the efficacy of methotrexate. By combining these 2 drugs with moderate dose radiotherapy survival outcomes should be optimal but with lower rates of neurotoxicity.

Comparison: TROG has previously performed a phase 2 study using methotrexate with high dose radiotherapy and this will allow comparison of survival and neurotoxicity rates.

Inclusion Criteria:

• Histologically proven primary CNS lymphoma.
• Absence of disease outside the CNS.
• ECOG performance status 0-3
• Negative HIV status.
• Peripheral blood counts with granulocytes >1.5 x 109L and platelets > 100 x 109L. Serum creatinine <150mmol/L. Serum bilirubin <1.5 times and AST <2 times upper limit of normal.
• Age >18 and <=70 years.
• Patients must give written informed consent.
• Corticosteroids prior to histological diagnosis are allowed.

Exclusion Criteria:

• Previous history of malignancy (other than non-melanomatous skin carcinoma, or carcinoma in situ of cervix completely excised).
• Patients who are pregnant or lactating.
• NYHA (New York State Heart Association classification) cardiac failure grade 3
• Macroscopic spinal thecal or spinal cord disease.