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Annals of Oncology Advance Access published online on October 26, 2008
Annals of Oncology, doi:10.1093/annonc/mdn628
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© The Author 2008. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oxfordjournals.org

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

G. Illerhaus1, R. Marks1, F. Müller1, G. Ihorst2, F. Feuerhake3, M. Deckert5, C. Ostertag4 and J. Finke1,*

1 Departments of Haematology and Oncology
2 Center of Clinical Trials
3 Department of Neuropathology
4 Stereotactic Neurosurgery, University Medical Center Freiburg, Freiburg
5 Department of Neuropathology, University Hospital, Cologne, Germany

* Correspondence to: Dr J. Finke, Department of Haematology and Oncology, University Medical Center Freiburg, Hugstetter Str. 55, 79106 Freiburg, Germany. Tel: +49-761-270-3364; Fax: +49-761-270-3658; E-mail: juergen.finke{at}uniklinik-freiburg.de

Background: To improve survival of elderly patients with primary central nervous system lymphoma (PCNSL), we conducted a phase II study with high-dose methotrexate (MTX) combined with procarbazine and CCNU. To reduce neurotoxicity, whole-brain irradiation was reserved 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 was no lower limit of Karnofsky performance status (KPS).

Results: Thirty patients with PCNSL (n = 29) or primary ocular lymphoma (n = 1) were included (median age 70 years, range 57–79 years). The median initial KPS was 60% (range 30%–90%). Best documented response in 27 assessable patients were 12 of 27 (44.4%) complete remissions, 7 of 27 (25.9%) partial remissions, and 8 of 27 (29.6%) disease progressions. Two patients died of probable treatment-related causes. With a median follow-up of 78 months (range 34–105), the 5-year overall survival is 33%. Eight of 30 patients (26.7%) are currently alive and well, six without signs of leukoencephalopathy.

Conclusion: The combination of high-dose MTX with procarbazine and CCNU is feasible and effective and results in a low rate of leukoencephalopathy. Comorbidity and toxicity remain of concern when treating PCNSL in elderly patients.

CNS lymphoma, elderly, methotrexate, neurotoxicity, PCNSL

Received for publication February 19, 2008. Revision received August 5, 2008. Accepted for publication August 7, 2008.


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