Fotemustine, Teniposide and Dexamethasone in Treating Patients with CNS Lymphoma

  • Wu, Jing-Jing (Institute of Clinical Medicine,The First Affiliated Hospital of Zhengzhou University) ;
  • Wang, Xin-Hua (Institute of Clinical Medicine,The First Affiliated Hospital of Zhengzhou University) ;
  • Li, Ling (Institute of Clinical Medicine,The First Affiliated Hospital of Zhengzhou University) ;
  • Li, Xin (Institute of Clinical Medicine,The First Affiliated Hospital of Zhengzhou University) ;
  • Zhang, Lei (Institute of Clinical Medicine,The First Affiliated Hospital of Zhengzhou University) ;
  • Sun, Zhen-Chang (Institute of Clinical Medicine,The First Affiliated Hospital of Zhengzhou University) ;
  • Fu, Xiao-Rui (Institute of Clinical Medicine,The First Affiliated Hospital of Zhengzhou University) ;
  • Ma, Wang (Institute of Clinical Medicine,The First Affiliated Hospital of Zhengzhou University) ;
  • Chang, Yu (Institute of Clinical Medicine,The First Affiliated Hospital of Zhengzhou University) ;
  • Zhang, Xu-Dong (Institute of Clinical Medicine,The First Affiliated Hospital of Zhengzhou University) ;
  • Han, Li-Juan (Institute of Clinical Medicine,The First Affiliated Hospital of Zhengzhou University) ;
  • Zhang, Ming-Zhi (Institute of Clinical Medicine,The First Affiliated Hospital of Zhengzhou University)
  • Published : 2014.06.15


Purpose: We developed and evaluated a regimen including fotemustine, teniposide and dexamethasone (FTD) for treating patients with central nervous system (CNS) lymphoma based on pharmacokinetic properties of individual agents and in combination. Patients and Methods: In a comparison study, 8 patients with primary CNS lymphoma (PCNSL) and 8 with secondary CNS lymphoma (SCNSL) were treated with FTD (comprising fotemustine 100 mg/m2, 1h infusion, day 1; teniposide 60 mg/m2, >0.5 h infusion, on day 2, 3, 4; dexamethasone 40 mg, 1h infusion, on day 1, 2, 3, 4 and 5; and methotrexate 12 mg, cytosine arabinoside 50 mg plus dexamethasone 5 mg intrathecally, on day 2 and 7). Cycles were repeated every 3 weeks. After response assessment, patients received whole brain radiotherapy. Results: Of the 8 PCNSL patients, 4 (50%) achieved CR and 3 (38%) PR, an overall response rate of 88%. Four patients (50%) were in continuing remission at the end of this study after a median follow-up of 30 months (range 10 to 56 months). Of the 8 SCNSL patients the overall response rate was 63% (CR+PR: 38%+25%). All responses were achievable with predictable toxicity mainly reflecting reversible myelosuppression. Conclusion: This study suggests that FTD could be an effective treatment for CNS lymphoma, and is worthy of further evaluation.


Supported by : Natural Science Foundation of China


  1. Abrey L, DeAngelis LE (2005). CNS lymphomas. Hematal Oncol Clin North Am, 14, 729-38.
  2. Abrey LE, Yahalom J, DeAngelis LM (2000). Treatment for primary CNS lymphoma: the next step. J Clin Oncol, 18, 3144-50.
  3. Andres J. M. Ferreri (2011). How I treat primary CNS lymphoma. Blood, 118, 510-22.
  4. Boehme V, Schmitz N, Zeynalova S, et al (2009). CNS events in elderly patients with aggressive lymphoma treated with modern chemotherapy (CHOP-14) with or without rituximab: an analysis of patients treated in the RICOVER-60 trial of the German High-Grade Non-Hodgkin Lymphoma Study Group (DSHNHL). Blood, 113, 3896-902.
  5. Batchelor T, Carson K, O'Neill A, et al (2003). Treatment of primary CNS lymphoma with methotrexate and deferred radiotherapy: a report of NABTT 96-07. J Clin Oncol, 21, 1044-9.
  6. Bierman P, Giglio P (2005). Diagnosis and treatment of central nervous system involvement in non-Hodgkin's lymphoma. Hematol Oncol Clin North Am, 19, 597-609.
  7. Boehme V, Zeynalova S, Kloess M, et al (2007). Incidence and risk factors of central nervous system recurrence in aggressive lymphoma--a survey of 1693 patients treated in protocols of the German High-Grade Non-Hodgkin's Lymphoma Study Group (DSHNHL). Ann Oncol, 18, 149-57.
  8. Chen TE (2006). Primary CNS lymphoma. Neurosurg Focus, 5, 21.
  9. DeAngelis LM, Seiferheld W, Schold SC, et al (2002). Combination chemotherapy and radiotherapy for primary central nervous system lymphoma: Radiation Therapy Oncology Group Study 93-10. J Clin Oncol, 20, 4643-8.
  10. FerreriAJ, Abrey LE, Blay JY, et al (2003). Summary statement on primary central nervous system lymphomas from the eighth international conference on malignant lymphoma, J Clin Oncol, 21, 2407-14.
  11. FerreriAJ, ReniM, ZoldanMC, et al (1996). Importance of complete staging in nonhodgkin's lymphoma presenting as a cerebral mass lesion. Cancer, 77, 827-33.<827::AID-CNCR4>3.0.CO;2-B
  12. FerreriAJ, Blay JY, Reni M, et al (2003). Prognostic scoring system for primary CNS lymphomas: the international extranodal lymphoma study group experience. J Clin Oncol, 21, 266-72.
  13. Jin J, Cai L, Liu ZM, et al (2013). miRNA-218 inhibits osteosarcoma cell migration and invasion by down-regulating of TIAM1, MMP2 and MMP9. Asian Pac J Cancer Prev, 14, 3681-4.
  14. G Vassal, I Boland, M J Terrier-Lacombe, et al (1998). Activity of fotemustine in medulloblastoma and malignant glioma xenografts in relation to O6-alkylguanine-DNA alkyltransferase and alkylpurine-DNA N-glycosylase activity. Clin Cancer Res, 4, 463-8.
  15. Hoang-Xuan K, Taillandier L, Chinot O, et al (2003). Chemotherapy alone as initial treatment for primary CNS lymphoma in patients older than 60 years: a multicenter phase II study (26952) of the European Organization for Research and Treatment of Cancer Brain Tumor Group. J Clin Oncol, 21, 2726-31.
  16. Jellinger KA, Paulus W (1992). Primary central nervous system lymphomas:An update. J Cancer Res Clin Oncol, 119, 7-27.
  17. Korfel A (2011). Prevention of central nervous system relapses in diffuse large B-cell lymphoma: which patients and how? Curr Opin Oncol, 23, 436-40.
  18. Li Q, Yin J, Wang X, et al (2013). B-cell Lymphoma 2 rs17757541 C> G polymorphism was associated with an increased risk of gastric cardiac adenocarcinoma in a Chinese population. Asian Pac J Cancer Prev, 14, 4301-6.
  19. Li LF, Wang HQ, Liu XM, et al (2013). Epirubicin inhibits soluble CD25 secretion by Treg cells isolated from diffuse large B-cell lymphoma patients. Asian Pac J Cancer Prev, 14, 1721-4.
  20. McAllister LD, Doolittle ND, Guastadisegni PE, et al (2000). Cognitive outcomes and long-term follow-up results after enhanced chemotherapy delivery for primary central nervous system lymphoma. Neurosurgery, 46, 51-60.
  21. National Cancer Institute (1988): Guidelines for Reporting of Adverse Drug Reactions. Bethesda, MD, Division of Cancer Treatment, National Cancer Institute.
  22. Mead GM, Bleehen NM, Gregor A, et al (2000). Amedical research council randomized trial in patients with primary cerebral nonhodgkin lymphoma:cerebral radiotherapy with and without cyclophos-phamide, doxorubicin, vincristine, and prednisone chemotherapy. Cancer, 89, 1359-70.<1359::AID-CNCR21>3.0.CO;2-9
  23. Miller DC, Hochberg FH, Harris NL, et al (1994). Pathology with clinical correlations of primary central nervous system non-Hodgkin's lymphoma. The Massachusetts General Hospital experience 1958-1989. Cancer, 74, 1383-97.<1383::AID-CNCR2820740432>3.0.CO;2-1
  24. Muggia FM (1994). Teniposide: overview of its therapeutic potential in adult cancers. Cancer Chemother Pharmacol, 34, S127-33.
  25. OBrien P, Roos D, Pratt G, et al (2000) . Phase II multicenter study of brief single-agent methotrexate followed by irradiation in primary CNS lymphoma. J Clin Oncol, 18, 519.
  26. Omuro AM, Taillandier L, Chinot O et al (2007), Temozolomide and methotrexate for primary central nervous system lymphoma in the elderly. J Neurooncol, 85, 207-11.
  27. Pels H, Schmidt-Wolf IG, Glasmacher A, et al (2003). Primary central nervous system lymphoma: results of a pilot and phase II study of systemic and intraventricular chemotherapy with deferred radiotherapy. J Clin Oncol, 21, 4489-95.
  28. Reni M, Ferreri AJ, Garancini MP, et al (1997). Therapeutic management of primary central nervous system lymphoma in immunocompetent patients:Results of a critical review of the literature. Ann Oncol, 8, 227-34.
  29. Rubenstein J, FerreriAJ, Pittaluga S et al (2008). Primary lymphoma of the central nervous system: epidemiology, pathology and current approaches to diagnosis, prognosis and treatment. Leuk Lymphoma, 49, 43-51.
  30. Sutcliffe SB, Gospodarowicz MK, Bush RS, et al (1985). Role of radiation therapy in localized non-Hodgkin's lymphoma. Radiother Oncol, 4, 211-23.
  31. Van Besien K, Ha CS, Murphy S, et al (1998). Risk factors, treatment, and outcome of central nervous system recurrence in adults with intermediate-grade and immunoblastic lymphoma. Blood, 91, 1178-84.
  32. Van Tellingen O, Boogerd W, Nooijen WJ, et al (1997). The vascular compartment hampers accurate determination of teniposide penetration into brain tumor tissue. Cancer Chemother Pharmacol, 40, 330-4.
  33. Wang X, Song ZF, Xie RM, et al (2013). Analysis of death causes of in-patients with malignant tumors in Sichuan Cancer Hospital of China from 2002 to 2012. Asian Pac J Cancer Prev, 14, 4399-402.
  34. Wang XF, Wu YH, Wang MS, et al (2014). CEA, AFP, CA125, CA153 and CA199 in malignant pleural effusions predict the cause. Asian Pac J Cancer Prev, 15, 363-8.
  35. Zhu WW, Kang L, Gao YP, et al (2013). Expression level of valosin containing protein is associated with prognosis of primary orbital MALT lymphoma. Asian Pac J Cancer Prev, 14, 6439-43.
  36. Zhang J, Zhu MY, Wang L, et al (2013). "Sandwich" chemotherapy (CT) with radiotherapy (RT) improves outcomes in patients with stage IE/IIE extranodal natural killer (NK)/T-cell Lymphomas. Asian Pac J Cancer Prev, 14, 4061-6.
  37. Zhang ZX, Shen CF, Zou WH, et al (2013). Exploration of molecular mechanisms of diffuse large B-cell lymphoma development using a microarray. Asian Pac J Cancer Prev, 14, 1731-5.

Cited by

  1. Prediction of Deoxypodophyllotoxin Disposition in Mouse, Rat, Monkey, and Dog by Physiologically Based Pharmacokinetic Model and the Extrapolation to Human vol.7, pp.1663-9812, 2016,
  2. Long-term remission of subcutaneous panniculitis-like T-cell lymphoma with central nervous system involvement: A case report vol.12, pp.1, 2016,
  3. Fotemustine, teniposide and dexamethasone versus high-dose methotrexate plus cytarabine in newly diagnosed primary CNS lymphoma: a randomised phase 2 trial pp.1573-7373, 2018,