Combined Treatment with High-Dose Methotrexate, Vincristine and Procarbazine, without Intrathecal Chemotherapy, Followed by Consolidation Radiotherapy for Primary Central Nervous System Lymphoma in Immunocompetent Patients

Abstract

Objectives: To assess the feasibility and the activity, as well as the efficacy to treat meninges, of chemotherapy (CHT) containing high-dose methotrexate (HD-MTX) followed by radiation therapy (RT), without intrathecal CHT, in patients with primary central nervous system lymphoma. Methods: Eligibility criteria were histologically proven diagnosis, disease limited to the CNS, age ≤70, ECOG performance status ≤3, HIV-negative and no prior treatment. Thirteen patients (1996–1999; median age 54 years) received two courses of vincristine 1.4 mg/m² day 1, MTX 3 g/m² days 3 and 10 and procarbazine 100 mg/m² days 1–14 every 4 weeks. Patients who achieved a complete remission were referred to RT, those with progressive disease were excluded from further study; all the remaining patients received a third course of CHT followed by RT. Results: Twelve patients responded to CHT (overall response rate = 92%, complete response rate = 77%): 9 underwent consolidation RT, 3 did not. Two patients experienced severe acute toxicity; lethal pulmonary thromboembolism and transient renal failure. Five patients relapsed: 2 after CHT and 3 after RT. Relapse was local in all cases, with a case of concomitant hepatic involvement. No cases of ocular or meningeal relapse were observed. In contrast to high-dose cytarabine-containing CHT, salvage therapy with temozolomide produced good results. Two patients died of treatment-related neurotoxicity. Six patients are alive with a median follow-up of 17 months, and a 2-year overall survival (OS) of 61%. The median survival of the 9 patients who completed the planned treatment is 25+ months with a 2-year OS of 80%. Conclusions: HD-MTX, procarbazine and vincristine followed by RT, without intrathecal therapy, produce similar results with respect to other HD-MTX-containing regimens. These results seem to suggest that adequate meningeal treatment is possible without intrathecal drug delivery, even in CSF-positive patients. Corroborating data from a larger series are, however, necessary. Temozolomide should be tested in relapsed patients in a phase II prospective trial.