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Annals of Oncology Advance Access originally published online on October 26, 2008
Annals of Oncology 2009 20(2):319-325; 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

hematologic malignancies

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.

Key words: 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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