A Non-Radiation-Containing, Intermediate-Dose Methotrexate (MTX) Regimen Resulted in Favorable Survival without Progression of Dementia in Elderly Patients with Primary Central Nervous System Lymphoma (PCNSL).

Survival of PCNSL (also termed as “DLBCL of the CNS” in the WHO classification ver. 4) has been improved in younger patients after the introduction of high-dose methotrexate (HD-MXT). In patients >60 with PCNSL, however, HD-MTX in combination with radiation therapy frequently causes neurotoxicities, particularly dementia, limiting their use. We used a non-radiation-containing, intermediate-dose MTX regimen for Japanese patients.

Consecutive patients >60 years newly diagnosed as PCNSL in our institute (n=13, median age 64) from 2005 to 2008 were treated with a slight modification of the protocol originally described by the European Organization for Research and Treatment of Cancer Brain Tumor (J Clin Oncol 21:2726, 2003). The induction regimen consisted of intravenous administration of intermediate-dose MTX (1 g/m²) on day 1, 10, and 20, in combination with ranimustine (40 mg/m² IV) on day 1, procarbazine (60 mg/m² po) on days 1–7, and methylpredonisolone (mPSL, 120 mg/m² IV) every other day for the first 3 weeks and 60 mg/m² (po) every other day for the next 3 weeks. Intrathecal chemotherapy (IT) with 15 mg MTX and 40 mg cytarabine was given on days 1, 5, 10 and 15.Complete response (CR) was defined as the absence of any contrast enhancement on the magnetic resonance imaging (MRI) in the brain, and partial response (PR) as a >50% reduction in the perpendicular diameters of the contrast-enhanced area without new lesions on MRI. If CR or PR was obtained, the maintenance therapy consisting of the same drugs, but without IV MTX on days 10 and 20, IT on days 5, 10, and 15, or any mPSL, was repeated 5 cycles every 6 weeks. To evaluate quality of life after the chemotherapy, we used Barthel Index and strength of the paralyzed side by physical examination. Development and progression of other neurotoxicities were evaluated by reviewing the clinical records. The Kaplan-Meier method was used to analyze survival.

All patients responded to induction, with CR and PR in 6 and 7 patients, respectively. All 13 patients started the maintenance therapy, of whom 10 have completed, 1 is in progress, and 2 had lymphoma progression and received other therapy. Two-year progression-free survival (PFS) and the period of median PFS were 42% and 20 months, respectively. Two-year overall survival (OS) and the period of median OS were 56% and 28 months, respectively. Neurotoxicities such as muscle weakness and dementia developed only in patients who suffered from relapse or progression of lymphoma. This protocol per se did not cause any acute and delayed neurotoxicities, including dementia.

Fifty six % 2-year OS without acute and delayed therapy-related neurotoxicities such as dementia was achieved by a non-radiation-containing, repeated intermediate-dose MTX regimen in Japanese patients. This may be among the protocols of choice for elderly PCNSL patients with regard to the efficacy and toxicity balance.

No relevant conflicts of interest to declare.