Japanese Journal of Clinical Oncology Advance Access published online on April 15, 2008
Japanese Journal of Clinical Oncology, doi:10.1093/jjco/hyn027
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© The Author (2008). Published by Oxford University Press. All rights reserved
Results of Treatment of 112 Cases of Primary CNS Lymphoma
1 Department of Neurosurgery, Brain Research Institute, Niigata University, Niigata
2 Department of Neurosurgery, Itoigawa General Hospital, Itoigawa, Niigata
3 Department of Neurosurgery, Niigata Prefectural Central Hospital, Takada, Niigata
4 Department of Neurosurgery, Toyama Prefectural Central Hospital, Toyama
5 Department of Neuropathology, Brain Research Institute, Niigata University, Niigata
6 Biostatistics Center, Kurume University School of Medicine, Kurume
7 Research Center of Innovative Cancer Therapy, Kurume University School of Medicine, Kurume, Fukuoka, Japan
For reprints and all correspondence: Ryuya Yamanaka, Research Center of Innovative Cancer Therapy, Kurume University School of Medicine, Asahimachi 67, Kurume, Fukuoka 830-0011, Japan. E-mail: ryaman{at}med.kurume-u.ac.jp
Received January 28, 2008; accepted March 6, 2008
Background: Chemotherapy with or without radiotherapy is the mainstay of treatment for primary central nervous system lymphoma (PCNSL). High-dose methotrexate (MTX) is the most effective drug available to treat these lesions, either as a single agent or in combination with other drugs. Due to the lack of well-conducted randomized trials, the optimal treatment remains controversial. Available retrospective studies are difficult to discuss, however, some common themes can be found.
Methods: One hundred and twelve patients with PCNSL were treated with four different regimens over a period of 24 years. Treatment regimens were: whole-brain irradiation (WBI) alone, MVP (MTX, vincristine, and predonisolone), ProMACE-MOPP hybrid (cyclophosphamide, pirarubicin, etoposide, vincristine, procarbazine, prednisone, and MTX) and R-MTX (rituximab, MTX, pirarubicin, procarbazine, and prednisone) combined-modality therapy.
Results: The median failure-free survival was 16 months, and the median overall survival (OS) was 24 months. The 2- and 5-year actuarial probability of survival was 52.4 ± 4.8% [95% confidence intervals (CI)] and 30.2 ± 4.8% (95% CI), respectively. The ProMACE-MOPP protocol, Karnofsky performance status (KPS), MTX dose and WBI were associated with good OS by univariate models. By multivariate analysis, MTX dose, WBI dose, and its square dose were significantly associated with good OS. 20–30 Gy WB, and 500 mg/m2 of MTX dose appeared important determinants of OS.
Conclusions: A modest dose of MTX (500 mg/m2) followed by reduced-dose WBI for patients who respond appears a feasible treatment approach that minimizes serious toxicity.
Key Words: methotrexate • neurotoxicity • primary CNS lymphoma • Pro-MACE-MOPP • radiotherapy