Yonsei Med J.  2011 Nov;52(6):1031-1034. 10.3349/ymj.2011.52.6.1031.

Combination Therapy with Rituximab and Temozolomide for Recurrent and Refractory Primary Central Nervous System Lymphoma

• Murakami M
• Fujimaki T
• Asano S
• Nakaguchi
• Yamada SM
• Hoya K
• Yamazaki K
• Ishida Y
• Matsuno A

• KMID: 1058828
• DOI: http://doi.org/10.3349/ymj.2011.52.6.1031

Abstract

High-dose methotrexate-based chemotherapy has extended survival in patients with primary central nervous system lymphoma (PCNSL). However, although salvage treatment is necessary in recurrent and refractory PCNSL, this has not been standardized. We herein describe the efficacy of a combination of rituximab and temozolomide (TMZ) in two consecutive patients with recurrent and refractory PCNSL. Based on the immunohistochemical study, case 1 had a non-germinal center B-cell-like (non-GCB) subtype, was positive for bcl-2 and negative for O6-methylguanine-DNA methyltransferase (MGMT). Case 2 was GCB subtype, bcl-2-, and MGMT+. Because of the positive expression of MGMT, interferon-beta was additionally given in case 2. Complete responses and partial responses were obtained after the third and fourth cycles of combination therapy, respectively. This was maintained for 12 months, with acceptable toxicity. The combination of rituximab and TMZ was effective in tumors with different immunohistochemical profiles. This combination therapy warrants further study in a larger population.

Keyword

Primary central nervous system lymphoma; rituximab; temozolomide; interferon-beta; salvage treatment

MeSH Terms

Aged
Antibodies, Monoclonal, Murine-Derived/*therapeutic use
Antineoplastic Agents/*therapeutic use
Central Nervous System Neoplasms/*drug therapy
Dacarbazine/*analogs & derivatives/therapeutic use
Drug Therapy, Combination/*methods
Humans
Lymphoma/*drug therapy
Male
Middle Aged
Neoplasm Recurrence, Local/drug therapy

Figure

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  Fig. 1 Gd-enhanced T1-weighted MRI of case 1: (A) MRI on admission in August 2007, showing the recurrent tumor in the right caudate head. (B) MRI after 3 cycles of combination therapy. The recurrent tumor in the right caudate head has disappeared. MRI, magnetic resonance image.

• 

  Fig. 2 Gd-enhanced T1-weighted MRI of case 2: (A) Initial MRI in March 2007 shows a large tumor in the left basal ganglia and temporal lobe. (B) MRI after treatment with high-dose MTX chemotherapy and radiotherapy shows partial response of the tumor. (C) MRI after 4 cycles of combination therapy. The tumor has reduced in size. (D) MRI in November 2008. Although the tumor in the left basal ganglia shows further shrinkage, multiple new lesions are observed. MRI, magnetic resonance image; MTX, methotrexate.

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