High-dose methotrexate combined with procarbazine and CCNU for primary CNS lymphoma in the elderly: results of a prospective pilot and phase II study

Background: To improve survival of elderly patients with primarycentral nervous system lymphoma (PCNSL), we conducted a phaseII study with high-dose methotrexate (MTX) combined with procarbazineand CCNU. To reduce neurotoxicity, whole-brain irradiation wasreserved for patients not responding to chemotherapy. Patients and methods: High-dose MTX was applied on days 1, 15,and 30, procarbazine on days 1–10, and CCNU on day 1.Study treatment comprised up to three 45-day cycles. There wasno lower limit of Karnofsky performance status (KPS). Results: Thirty patients with PCNSL (n = 29) or primary ocularlymphoma (n = 1) were included (median age 70 years, range 57–79years). The median initial KPS was 60% (range 30%–90%).Best documented response in 27 assessable patients were 12 of27 (44.4%) complete remissions, 7 of 27 (25.9%) partial remissions,and 8 of 27 (29.6%) disease progressions. Two patients diedof probable treatment-related causes. With a median follow-upof 78 months (range 34–105), the 5-year overall survivalis 33%. Eight of 30 patients (26.7%) are currently alive andwell, six without signs of leukoencephalopathy. Conclusion: The combination of high-dose MTX with procarbazineand CCNU is feasible and effective and results in a low rateof leukoencephalopathy. Comorbidity and toxicity remain of concernwhen treating PCNSL in elderly patients. Key words: CNS lymphoma, elderly, methotrexate, neurotoxicity, PCNSLReceived for publication February 19, 2008. Revision received August 5, 2008. Accepted for publication August 7, 2008.