Topotecan as salvage therapy for relapsed or refractory primary central nervous system lymphoma.

Department of Neurosurgery, Medical College of Georgia, Augusta, GA, USA.
Journal of Neuro-Oncology (Impact Factor: 2.79). 02/2008; 86(2):211-5. DOI: 10.1007/s11060-007-9464-6
Source: PubMed

ABSTRACT 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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    ABSTRACT: There is comparatively limited therapy for recurrent primary central nervous system lymphoma (PCNSL). Salvage therapies include re-challenge with high-dose methotrexate (HD-MTX), whole brain radiotherapy, temozolomide, topotecan and premetrexed. Bendamustine is a novel bifunctional alkylator with established activity in B cell systemic lymphomas but never previously evaluated in PCNSL. The objective of the current study was to assess response and toxicity of bendamustine in recurrent PCNSL following prior salvage therapy in a retrospective case series. Twelve adults [six males; six females: median age 59 years (range 43-74)] with HD-MTX refractory recurrent PCNSL were treated with bendamustine. All patients were treated at second recurrence following failure of prior salvage therapy. A cycle of bendamustine was defined as two consecutive days of treatment (100 mg/m(2)/day) administered once every 4 weeks (maximum number of cycles 6). Toxicities seen were Grade 2 (24 episodes in 10 patients) and 3 (10 episodes in 5 patients) only and included lymphopenia (8 patients), hyperglycemia (7 patients), fatigue (7 patients) and nausea (4 patients). The median number of cycles of therapy was 3.5 (range 1-6). Radiographic response was progressive disease in 5 (42 %), stable disease in 1 (8 %), partial response in 3 (25 %) and complete response in 3 (25 %). Median progression free survival (PFS) was 3.5 months (range 1-14 months) and 6-month PFS was 33 %. In this small retrospective series of select patients with recurrent PCNSL refractory to HD-MTX, bendamustine appears to have modest single agent activity with manageable toxicity. Confirmation in a larger series of similar patients is required.
    Journal of Neuro-Oncology 03/2014; · 3.12 Impact Factor
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    ABSTRACT: Background and aims Primary Central Nervous System Lymphoma (PCNSL) is a rare disease, about 2-6.6% of all primary intracranial tumors. The incidence of PCNSL raised recently in both immunocom-promised and immunocompetent people. Surgery is usually ineffective for PCNSL and does not prolong survival because of its infiltrative growth pattern. The mainstay of PCNSL management consists of radiotherapy or chemotherapy but both cannot be initiated before a definite diagnosis is established. Although stereotactic biopsy is the method of choice for definite diagnosis, new imaging modalities (MR spectroscopy) and regression of the lesion with steroid administration are helpful as well. Methods We present a patient case that combined rapid deterioration of his neurological status, failure to respond to steroid administration and a strong possibility (based on imaging) of high grade malignancy. The patients was led to craniotomy and partial excision of the lesion. Results Histology diagnosed the lesion as PCNSL. The patient displayed marked improvement in his neurological status in the immediate postoperative period, even before the initiation of chemotherapy. He has already completed 6 circles of chemotherapy and is prepared to have autologous bone marrow transplantation. Conclusions It is our belief that further concrete imaging criteria need to be established for the likelihood of diagnosis of PCNSL, in order to avoid unnecessary invasive diagnostic and treatment procedures.
    European Association of Neurosurgical Societies (EANS) Annual Meeting 2013, Tel Aviv, Israel; 11/2013
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    ABSTRACT: This study evaluated the efficacy and safety of a new regimen consisting of Topotecan, Ifosfamide, Etoposide, and L-asparaginase (TIEL) in treating aggressive T-cell lymphoma. Twenty-four patients were included in the research, eighteen males and six females. Half of the patients were in stages III and IV, and nearly half of them experienced failure of at least one regimen. Eleven were diagnosed as peripheral T-cell lymphoma (PTCL), five extranodal NK/T-cell lymphoma, non-specific, four angioimmunoblastic, and four anaplastic large-cell lymphoma (2 ALK positive). Patients were given 98 cycles of TIEL altogether. The responsive rate to TIEL was 76.9 % among 13 cases who received the regimen as the first-line treatment. Among 11 cases, TIEL was the second- or more-line treatment, the responsive rate was 63.6 %. The median PFS was 32.0 ± 21.0 (95 % CI 0-73.29) months. Median overall survival (OS) was not reached yet. Approximately 41.3 % of patients showed the third- to fourth-degree hematological side effects. Non-hematological toxicity included nausea, vomiting, diarrhea, and abnormal liver function. Among those patients received L-asparaginase, nine experienced mild abnormal coagulation function after 7 days of initiating chemotherapy, and no pancreatic injury was found. TIEL regimen is effective for aggressive T-cell lymphoma with controllable side effect and can be used for more patients.
    Medical Oncology 01/2015; 32(1):402. · 2.06 Impact Factor