Topotecan as salvage therapy for relapsed or refractory primary central nervous system lymphoma. J Neurooncol 86(2): 211-215

Harvard University, Cambridge, Massachusetts, United States
Journal of Neuro-Oncology (Impact Factor: 3.07). 02/2008; 86(2):211-5. DOI: 10.1007/s11060-007-9464-6
Source: PubMed


Treatment for patients with refractory or relapsed primary CNS lymphoma (PCNSL) remains unsatisfactory. Topotecan is an intravenous topoisomerase I inhibitor with good CSF penetration and documented efficacy in patients with relapsed systemic non-Hodgkin's lymphoma. In this study 15 patients with refractory or relapsed PCNSL were treated with intravenous topotecan (1.5 mg/m(2)) for five consecutive days during each 21-day cycle. All 15 patients had measurable, contrast-enhancing tumor on cranial MRI at the time of relapse. Three (20%) patients achieved a complete response after one, three and four cycles, respectively, while three (20%) patients achieved a partial response after two cycles each, for a total response proportion of 40%. Three patients had stable disease at the end of topotecan treatment. Six patients (40%) had progressive disease during treatment. Median overall survival was 981 days (95% CI: 275, NA) and median progression free survival was 60 days (95% CI: 46, 945). Three out of 15 patients had grade 3 thrombocytopenia. Six out of 15 patients had grade 3 neutropenia, while 5/15 patients had grade 4 neutropenia, and 13/15 patients received g-CSF at some point during treatment. There were no deaths directly related to treatment toxicity. Our study shows that topotecan, as a salvage therapy in patients with relapsed or refractory PCNSL, is associated with an overall response proportion of 40% and should be considered in patients who have failed prior methotrexate-based chemotherapy and/or whole brain irradiation. However, progression is frequent and early and most patients required growth factor support due to myelotoxicity.

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    • "Topotecan also has been found to be useful in salvage treatment with response rates of 33-40 % and median OS of 8.4 and 35 months in two different studies [70, 71]. Other salvage treatments have included combination of etoposide, ifosfamide, and cytarabine, and procarbazine, lomustine, and vincristine with response rates of 37 % and 86 %, respectively, and 1-year OS of 41 % and 57 %, respectively [72, 73]. "
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    ABSTRACT: Opinion statement Therapeutic options are limited in primary central nervous system lymphoma (PCNSL) with no uniform consensus on optimal management and few published, randomized trials. High-dose methotrexate in combination with other chemotherapeutic agents forms the mainstay of treatment. There hasn’t been much progress beyond high-dose methotrexate in this disease, and although results from trials using high-dose chemotherapy and autologous stem-cell transplant seem promising, these need to be further validated. Moreover, the role of whole brain radiation in the upfront setting remains to be determined. However, international efforts in this direction are underway, with ongoing randomized trials in newly diagnosed PCNSL, more research on the molecular pathogenesis and biomarkers, and the use of novel agents in salvage therapy. There also is emphasis on quality of life parameters and neurocognitive status. Future treatment options should optimize high-efficacy rates while minimizing the risk of neurotoxicity.
    Current Treatment Options in Oncology 12/2013; 14(4). DOI:10.1007/s11864-013-0252-6 · 3.24 Impact Factor
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    ABSTRACT: Primary central nervous system lymphoma (PCNSL) is a rare subtype of extranodal non-Hodgkin lymphoma (NHL) that arises from the brain parenchyma, eyes, cerebrospinal fluid, meninges or spinal cord without evidence of systemic spread. It has had an increase during last 3 decades, accounting for ∼3% of all CNS malignancies in the United States from 1998 to 2002.
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    ABSTRACT: Primary central nervous system lymphoma (PCNSL) comprises approximately 5 % of all primary brain tumors. During the past two decades the incidence of PCNSL has increased, and as a result clinical research to determine the optimal treatment for PCNSL patients also has increased. Diagnosis is based on histopathologic findings traditionally established by biopsy only. More recent data raise controversy and challenges this biopsy-only paradigm, showing a potential advantage for surgical resection with progression-free survival (PFS) and overall survival (OS). Using high-dose intravenous (IV) methotrexate-based chemotherapy alone or as part of a regimen can lead to disease cure. The role of whole brain radiotherapy (WBRT) remains controversial and more frequently is omitted to avoid potential delayed neurocognitive effects, especially in patients older than age 60 years. Newer data from Memorial Sloan Kettering Cancer Center (MSKCC) using five cycles of Rituximab, Methotrexate, Vincristine, and Procarbazine (R-MVP) followed by low-dose WBRT (2,340 cgy), and then two cycles of Ara-C had excellent disease control with low neuro-toxicity and is now the basis of an ongoing RTOG (Radiation Treatment Oncology Group) trial comparing early versus delayed WBRT. Other chemotherapeutics and novel treatments, such as autologous stem cell transplantation, are being studied for potential use in PCNSL. Unlike many other primary brain tumors seen in adults, PCNSL is potentially curable; therefore, balancing treatment decisions with long-term neurocognitive effects and toxicities is crucial.
    Current Treatment Options in Oncology 03/2013; 14(2). DOI:10.1007/s11864-013-0227-7 · 3.24 Impact Factor
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