Abstract
Introduction: High-dose methotrexate (HD-MTX)-based chemotherapy with whole brain irradiation (WBRT) improves the prognosis of PCNSL. However, the high neurotoxicity rates observed, especially in the elderly, raised interest in chemotherapy-only treatments. Withholding radiotherapy substantially decreases the risk of neurotoxicity, however, disease control may be compromised. Therefore, developing novel treatment for the elderly patients is crucial. To assess the efficacy and toxicity of induction immunochemotherapy with rituximab (RIT) and HD-MTX, maintenance chemotherapy with HD-MTX and deferred WBRT in the treatment of elderly PCNSL patients, we conducted a retrospective analysis. Materials and Methods: Newly diagnosed elderly PCNSL patients (median age: 74 years) received biweekly RIT/ HD-MTX (375 mg/m(2)/dose; 3.5g/m(2)/dose) for 6 cycles followed by monthly RIT/MTX for 2 cycles (induction) and then were treated differently according to radiological response. With CR patents, HD-MTX was continued with every 3 months (maintenance) for 2 years. For PD patients, immunochemotherapy was interrupted and WBRT initiated immediately. Patients with PR and SD were treated with alternative chemotherapy with temozolomide and/or stereotactic radiotherapy or WBRT. Results: Twenty-eight patients were treated with the RIT/HD-MTX regimen. In 26 patients suitable for radiographic evaluation, 61.5% (16/26) had a CR, 23.1% (6/26) had a PR, 3.8 % (1/26) had a SD and 11.5% (3/26) had a PD. The median PFS was 24.6 months and median OS was 28.2 months for the entire cohort. Grade III-IV toxicities were observed in 8 of 28 patients and included neutropenia in 17.9%, thrombocytopenia in 3.6%, pneumonia in 10.7%, elevation of aminotransferases in 3.6%, and hyponatremia in 3.6%. Patients achieving a CR after induction immunochemotherapy (n=16) had a significantly longer OS (65.8 months) and PFS (52.4 months) than patients with less than CR (n=10) (OS: 13.9 months; PFS: 9.3 months) (P<.0001). Conclusions: The RIT/HD-MTX regimen and maintenance chemotherapy with HD-MTX seems to play a favorable role in elderly PCNSL patients with mild toxicity.