Clinical-patient studies

Journal of Neuro-Oncology

, Volume 86, Issue 2, pp 211-215

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

  • Alfredo D. VoloschinAffiliated withDepartment of Neurosurgery, Medical College of Georgia
  • , Rebecca BetenskyAffiliated withDepartment of Biostatistics, Harvard School of Public Health
  • , Patrick Y. WenAffiliated withDepartment of Neurology, Brigham and Women’s HospitalCenter For Neuro-Oncology, Dana Farber/Brigham and Women’s Cancer CenterHarvard Medical School
  • , Fred HochbergAffiliated withHarvard Medical SchoolDepartment of Neurology, Stephen E. and Catherine Pappas Center for Neuro-Oncology, Yawkey 9E, Massachusetts General Hospital
  • , Tracy BatchelorAffiliated withHarvard Medical SchoolDepartment of Neurology, Stephen E. and Catherine Pappas Center for Neuro-Oncology, Yawkey 9E, Massachusetts General HospitalDepartment of Radiation Oncology and Neurology, Massachusetts General Hospital Email author 

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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/m2) 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.

Keywords

Primary CNS lymphoma Salvage therapy Topotecan Radiographic response Survival