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High-dose cytarabine salvage therapy for recurrent primary CNS lymphoma

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Abstract

Treatment of recurrent primary CNS lymphoma (PCNSL) though not standardized most often utilizes whole brain radiotherapy, re-challenge with high-dose methotrexate, or administration of an alkylating chemotherapy. High-dose cytarabine (HD-araC) has been advocated as an active agent in PCNSL but limited information exists regarding single agent activity in the recurrent setting. A retrospective review of 14 patients (10 males, 4 females: median age 60 years) with recurrent PCNSL treated at second recurrence with single agent HD-araC. HD-araC was administered at 3gm/m2 over a 3-h infusion every 12 h for a total of 4 doses (defined as a cycle of therapy). GM-CSF was administered at conclusion of HD-araC. Patients were clinically and radiographically evaluated every 4-weeks. Common toxicity criteria Grade 3 or 4 toxicity included thrombocytopenia (11 patients; 79 %), anemia (10; 71 %), fatigue (8; 57 %), mucositis (8; 57 %), neutropenia (8; 57 %) and neutropenic fever (5; 36 %). No patient discontinued therapy due to toxicity nor were there any treatment-related deaths. Best response to HD-araC was stable disease in 6 patients (43 %), partial response in 5 (36 %) and progressive disease in 3 (21 %). Median progression free survival 3 months (range 2–5 months; 95 % CI 2–4 months) and progression free survival was 0 % at 6-months. Median survival after onset of HD-araC was 12 months (range 3–18+ months; 95 % CI 3–15 months). Single agent HD-araC has limited activity in recurrent PCNSL and is associated with significant toxicity in this small retrospective study.

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References

  1. Rubenstein JL, Hsi ED, Johnson JL et al (2013) Intensive chemotherapy and immunotherapy in patients with newly diagnosed primary CNS lymphoma: CALGB 50202 (Alliance 50202). J Clin Oncol 31:3061–3068

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  2. Wang CC, Carnevale J, Rubenstein JL (2014) Progress in central nervous system lymphomas. Br J Haematol 166:311–325

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  3. Ponzoni M, Issa S, Batchelor TT, Rubenstein JL (2014) Beyond high-dose methotrexate and brain radiotherapy: novel targets and agents for primary CNS lymphoma. Ann Oncol 25:316–322

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  4. Rubenstein JL, Gupta NK, Mannis GN, Lamarre AK, Treseler P (2013) How I treat CNS lymphomas. Blood 122:2318–2330

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  5. Morris P, Correa DD, Yahalom J et al (2013) Rituximab, methotrexate, procarbazine and vincristine followed by consolidation reduced-dose whole brain radiotherapy and cytarabine in newly diagnosed primary CNS lymphoma: final results and long-term outcome. J Clin Oncol 31:3971–3979

    Article  PubMed  CAS  Google Scholar 

  6. Ferreri AJ, Ciceri F, Brandes AA et al (2014) MATILDE chemotherapy regimen for primary CNS lymphoma: results at a median follow-up of 12 years. Neurology 82:1370–1373

    Article  PubMed  CAS  Google Scholar 

  7. Chamberlain MC, Johnston SK (2010) High-dose methotrexate and rituximab with deferred radiotherapy for newly diagnosed primary B-cell CNS lymphoma. Neuro-Oncology 12:736–744

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  8. Ferreri AJM, Reni M, Foppoli M, International Extranodal Lymphoma Study Group (IELSG) et al (2009) High-dose cytarabine plus high-dose methotrexate versus high-dose methotrexate alone in patients with primary CNS lymphoma: a randomised phase 2 trial. Lancet 374:1512–1520

    Article  PubMed  CAS  Google Scholar 

  9. Thiel E, Korfel A, Martus P et al (2010) High-dose methotrexate with or without whole brain radiotherapy for primary CNS lymphoma (G-PCNSL-SG-1): a phase 3, randomised, non-inferiority trial. Lancet Oncol 11:1036–1047

    Article  PubMed  CAS  Google Scholar 

  10. Wieduwilt MJ, Valles F, Issa S et al (2012) Immunochemotherapy with intensive consolidation for primary CNS lymphoma: a pilot study and prognostic assessment by diffusion-weighted MRI. Clin Cancer Res 18:1146–1155

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  11. DeAngelis LM, Yahalom J, Thaler HT et al (1992) Combined modality therapy for primary CNS lymphoma. J Clin Oncol 10:635–643

    PubMed  CAS  Google Scholar 

  12. Pentsova E, DeAngelis L, Omuro A (2014) Methotrexate re-challenge for recurrent primary central nervous system lymphoma. J Neuooncol 117:161–165

    Article  CAS  Google Scholar 

  13. Reni M, Zaja F, Mason W et al (2007) Temozolomide as salvage treatment in primary brain lymphomas. Br J Cancer 96:864–867

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  14. Herrlinger U, Brugger W, Bamberg M et al (2000) PCV salvage chemotherapy for recurrent primary CNS lymphoma. Neurology 54:1707–1708

    Article  PubMed  CAS  Google Scholar 

  15. Reni M, Ferreri AJ (2001) Therapeutic management of refractory or relapsed primary central nervous system lymphomas. Ann Hematol 80(suppl 3):B113–B117

    PubMed  CAS  Google Scholar 

  16. Frei E, Bickers JN, Hewlett JS et al (1979) Dose schedule and antitumor studies of arabinosyl cytosine. Cancer Res 29:1325–1332

    Google Scholar 

  17. Ho DHW, Frei E (1971) Clinical pharmacology of 1-B-D-arabinofuranosylcytosine. Clin Pharmacol Ther 12:944–954

    Article  PubMed  CAS  Google Scholar 

  18. Slevin ML, Piall EM, Aherne GW, Harvey VJ, Johnstoin HA, Lister TA (1983) Effect of dose and schedule on pharmacokinetics of high-dose cytosine arabinoside in plasma and cerebrospinal fluid. J Clin Oncol 1:546–551

    PubMed  CAS  Google Scholar 

  19. Macdonald DR, Cascino TL, Schold SC et al (1990) Response criteria for phase II studies of supratentorial malignant glioma. J Clin Oncol 8:1277–1280

    PubMed  CAS  Google Scholar 

  20. Nguyen PL, Chakravarti A, Finkelstein DM et al (2005) Results of whole-brain radiation as salvage of methotrexate failure for immunocompetent patients with primary CNS lymphoma. J Clin Oncol 23:1507–1513

    Article  PubMed  Google Scholar 

  21. Raizer JJ, Rademaker A, Evens AM et al (2012) Pemetrexed in the treatment of relapsed/refractory primary central nervous system lymphoma. Cancer 118:3743–3748

    Article  PubMed  CAS  Google Scholar 

  22. Fischer L, Thiel E, Klasen HA et al (2006) Prospective trial on topotecan salvage therapy in primary CNS lymphoma. Ann Oncol 17:1141–1145

    Article  PubMed  CAS  Google Scholar 

  23. Soussain C, Suzan F, Hoang-Xuan K et al (2001) Results of intensive chemotherapy followed by hematopoietic stem-cell rescue in 22 patients with refractory or recurrent primary CNS lymphoma or intraocular lymphoma. J Clin Oncol 19:742–749

    PubMed  CAS  Google Scholar 

  24. Chamberlain MC (2014) Salvage therapy with bendamustine for methotrexate refractory recurrent primary CNS lymphoma: a retrospective case series. J Neurooncol 18:155–162

    Article  Google Scholar 

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Acknowledgments

I would like to express my appreciation to Dr. Bernardo Goulart for statistical assistance and for the expert administrative assistance provided by Alisa Clein.

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  1. Department of Neurology and Neurological Surgery, Fred Hutchinson Cancer Research Institute, Seattle Cancer Care Alliance, University of Washington, 825 Eastlake Avenue East, POB 19023, Mailstop: G-4940, Seattle, WA, 98109-1023, USA

    Marc C. Chamberlain

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Correspondence to Marc C. Chamberlain.

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Chamberlain, M.C. High-dose cytarabine salvage therapy for recurrent primary CNS lymphoma. J Neurooncol 126, 545–550 (2016). https://doi.org/10.1007/s11060-015-1994-8

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  • DOI: https://doi.org/10.1007/s11060-015-1994-8

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