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Intravenous Methotrexate as Initial Treatment for Primary Central Nervous System Lymphoma: Response to Therapy and Quality of Life of Patients

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Abstract

In anticipation of a consortium study of methotrexate (MTX) therapy provided to patients with primary central nervous system lymphoma (PCNSL) we have provided intravenous MTX without irradiation therapy to 31 non-immunosuppressed individuals. Twenty (65%) achieved complete response and 11 (35%) partial response to therapy. For the 31 patients the median survival was 30.43 months with an actuarial median follow up time of 30.69 months. The 2+ year survival was 63% for all patients and 90% for complete responders. Of 375 drug cycles, grade 3 leukopenia was identified in 3 cycles, mucositis in 6 cycles and delayed drug clearance in 47 cycles. Recurrences included brain (9/20) and/or spinal fluid (2/20). The median Karnofsky scale improved from 40 (10–80) prior to therapy to 90 after treatment. Eleven patients, in complete response for a median of 22+ months after diagnosis were evaluated using 4 instruments that assess Quality of Life Functional Assessment of Cancer Therapy – Brain (FACT-BR) modified, Symptom Questionnaire, Social Adjustment Scale-Self-Report and Problem Solving Inventory. Their psychosocial adjustment, well-being and stress coping abilities were comparable to the normative groups. Further there was no evidence of any MTX-induced, Magnetic Resonance Imaging (MRI)-detected encephalopathy in these individuals and there was preservation of clinical cognition and memory. We conclude that therapy with MTX, without radiation can be used in PCNSL patients without limitations of age or pretreatment Karnofsky scores. Further rates of response and median survival approach those of therapies using multiple drugs and radiation, but with a less likely risk of dementia.

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References

  1. Corn BW, Marcus SM, Topham A, HauckW, Curran WJ Jr: Will primary central nervous system lymphoma be the most frequent brain tumor diagnosed in the year 2000? Cancer 79: 2409–2413, 1997

    PubMed  Google Scholar 

  2. Cot´e TR, Manns A, Hardy CR, Yellin FJ, Hartge P, AIDS/Cancer Study Group: J Natl Cancer Inst 88: 675–679, 1996

    PubMed  Google Scholar 

  3. Miller DC, Hochberg FH, Harris NL, Gruber ML, Louis DN, Cohen H: Pathology with clinical correlations of primary central nervous system/Non-Hodgkin's lymphoma. Cancer 74: 1383–1397, 1994

    PubMed  Google Scholar 

  4. Eby NL, Grufferman S, Flannelly CM, Schold SC, Vogel FS, Burger PC: Increasing incidence of primary brain lymphoma in the U.S. Cancer 62: 2461–2465, 1988

    PubMed  Google Scholar 

  5. Jellinger J, Radaskiewicz TH, Slowick F: Primary malignant lymphomas of the central nervous system in man. Acta Neuropathologica (Suppl 6): 95–102, 1975

  6. Henry JM, Heffner RR, Dillard SH, Earle KM, Davis RL: Primary malignant lymphomas of the central nervous system: Cancer 34: 1293–1302, 1974

    PubMed  Google Scholar 

  7. Nelson DF, Martz KL, Bonner H, Nelson JS, Newall J, Kerman HD, Thomson JW, Murray KJ: Non-Hodgkin's lymphoma of the brain: Can high dose, large volume radiation therapy improve survival? Report on a prospective trial by the radiation rherapy oncology group (RTOG): TROG 8315. Int J Radiat Oncol Biol Phys 23: 9–17, 1992

    PubMed  Google Scholar 

  8. Chamberlain MC, Levin VA: J Neuro-Oncol 14: 271–275, 1992

    Google Scholar 

  9. Shibamoto Y, Tsutsui K, Dodo Y, Yamabe H, Shima N, Abe M: Improved survival rate in primary intracranial lymphoma treated by high-dose radiation and systemic vincristine-doxorubicin-cyclophosphamide-prednisolone chemotherapy. Cancer 65: 1907–1912, 1990

    PubMed  Google Scholar 

  10. Pollack IF, Lunsford LD, Flickinger JC, Dameshek HL: Prognostic factors in the diagnosis and treatment of primary central nervous system lymphoma. Cancer 63: 939–947, 1989

    PubMed  Google Scholar 

  11. Freeman CR, Shustik C, Brisson ML, Meagher-Villemure K, Dylewski I: Primary malignant lymphoma of the central nervous system. Cancer 58: 1106–1111, 1986

    PubMed  Google Scholar 

  12. Abelson HT, Kufe DW, Skarin AT, Major P, Ensminger W, Beardsley GP, Cancellos GP: Treatment of central nervous system tumors with methotrexate. Cancer Treat Rep 65(Supp l): 137–140, 1981

    Google Scholar 

  13. Crossen JR, Garwood D, Neuwelt EA: Neurobehavioral sequelae of cranial irradiation in adults: a review of radiation-induced encephalopathy. J Clin Oncol 12: 627–642, 1994 267

    PubMed  Google Scholar 

  14. Sheline G, Wara WM, Smith V: Therapeutic irradiation and brain injury. Int J Radiation Oncology Biol Phys 6: 1215–1228, 1980

    Google Scholar 

  15. Cher L, Glass J, Harsh GR, Hochberg FH: Therapy of primary central nervous system lymphoma with methotrexatebased chemotherapy and deferred radiotherapy: preliminary results. Neurology 46: 1757–1759, 1996

    PubMed  Google Scholar 

  16. Freilich RJ, Delattre JY, Monjour A, DeAngelis LM: Chemotherapy without radiation therapy as initial treatment for primary CNS lymphoma in older patients. Neurology 46: 435–439, 1996

    PubMed  Google Scholar 

  17. Glass J, Shustik C, Hochberg FH, Cher L, Gruber ML: Therapy of primary central nervous system lymphoma with preirradiation methotrexate, cyclophosphamide, doxorubicin, vincristine and dexamethasone (MCHOD). J Neuro-Oncol 30: 257–265, 1996

    Google Scholar 

  18. Glass J, Gruber ML, Cher L, Hochberg FH: Pre-irradiation MTX chemotherapy of primary central nervous system lymphoma: long term outcome. J Neurosurgery 81: 188–195, 1994

    Google Scholar 

  19. Lachance DH, Briezel DM, Gockerman JP, Halperin EC, Burger PC, Boyko OB, Brown MT, Schold SC Jr: Cyclophosphamide, doxorubicin, vincristine, and prednisone for primary central nervous system lymphoma: shortduration response and multi-focal intracerebral recurrence preceding radiotherapy. Neurology 44: 1721–1727, 1994

    PubMed  Google Scholar 

  20. DeAngelis LM, Yaholom J, Thaler HT, Kher U: Combined modality therapy for primary CNS lymphoma. J Clin Oncol 10: 635–643, 1992

    PubMed  Google Scholar 

  21. Schultz C, Scott C, Wasserman T, Fisher B, Abrams R, Sherman W, Fetell M, Nelson J: Pre-irradiation chemotherapy (CTX) with cytoxan, adriamycin, vincristine, and decadron (CHOD) for primary central nervous system lymphomas (PCNSL): Initial report of radiation therapy oncology group (RTOG) protocol 88–06. ProcAmSoc Clin Oncol 13: 174, 1994

    Google Scholar 

  22. Watne K, Scott H, Hager B, Lindegaard MW, Nome O, Abrahamsen AF, Hirschberg H: Primary malignant lymphoma of the brain:Areport of 24 cases from the Norwegian radium hospital. Acta Oncol 31: 545–550, 1992

    PubMed  Google Scholar 

  23. Neuwelt EA, Goldman DL, Dahlborg SA, Crossen J, Ramsey F, Roman-Goldstein S, Braziel Rita, Dana B: Primary CNS lymphoma treated with osmotic blood-brain barrier disruption: prolonged survival and preservation of cognitive function. J Clin Oncol 9: 1580–1590, 1991

    PubMed  Google Scholar 

  24. Bessell EM, Punt J, Firth J, Hope T, Holland I, Lowe J: Primary non-Hodgkin's lymphoma of the central nervous system: Phase II study of chemotherapy (BVAM) prior to radiotherapy. Clin Oncol (R Coll Radiol) 3: 193–198, 1991

    Google Scholar 

  25. Soci´e G, Piprot-Chauffat C, Schlienger M, Legars D, Thurel C, Mikol J, Ifran N, Briere J, Pene F, Gindrey-Vie B, Marin JL, Desablens B, Laugier A: Primary lymphoma of the central nervous system. Cancer 65: 322–326, 1990

    PubMed  Google Scholar 

  26. Brada M, Dearnaley D, Horwich A, Bllom HJG: Management of primary cerebral lymphoma with initial chemotherapy: Preliminary results and comparison with patients treated with radiotherapy alone. Int J Radiation Oncology Biol Phys 18: 787–792, 1990

    Google Scholar 

  27. Gabbai AA, Hochberg FH, Linggood RM, Bashir R, Holteman K: High-dose methotrexate for non-AIDS primary central nervous system lymphoma. J Neurosurg 70: 190–194, 1989

    PubMed  Google Scholar 

  28. Stewart FJ, Russell N, Dennery J, Richard M, Atack E, Eapen L: Cyclophosphamide, adriamycin, vincristine, and dexamethasone in the treatment of bulky central nervous system lymphomas. J Neuro-Oncol 2: 289, 1984

    Google Scholar 

  29. Hoang-Xaun K, Chinot O, Frenay M, Taillandier L, Hildebrand J, Monjour A, Van den Bent M, Sahmoud T, Poisson M, Delattre JY: Chemotherapy alone as initial treatment of primary central nervous system lymphoma (PCNSL) in older patients. (Abstracts) Neurology 48: A17, 1997

    PubMed  Google Scholar 

  30. ShermanW, Balmaceda C, Nichols G, Mears G, Antman K: Feasibility of 3 g/m2 of intravenous methotrexate (IVMTX) for primary central nervous system lymphoma (PCNSL). (Abstracts) Neurology 48: A17–18, 1997

    PubMed  Google Scholar 

  31. Kaplan E, Meier P: Nonparametric estimation from incomplete observation. J Am Stat Assoc 53: 457–481, 1958

    Google Scholar 

  32. Mackworth N, Fobair P, Prados MD: Quality of life selfreports from 200 brain tumor patients: comparisons with Karnofsky performance scores. J Neuro-Oncol 14: 243–253, 1992

    Google Scholar 

  33. Weitzner MA, Meyers CA, Gelke CK, Byrne KS, Cella DF, Levin VA: The functional assessment of cancer therapy (FACT) scale: Development of a brain subscale and the revalidation of the general version (FACT-G) in patients with primary brain tumors. Cancer 75: 1151–1161, 1995

    PubMed  Google Scholar 

  34. Kellner R: A symptom questionnaire. J Clin Psychiatry 48: 268–274, 1987

    PubMed  Google Scholar 

  35. Kellner R, Abbott P, Pathak D, Winslow WW, Umland BE: Hypochondriacal beliefs and attitudes in family practice and psychiatric patients. Int J Psychiatry Med 13: 127–139, 1984

    Google Scholar 

  36. Weissman MM, Bothwell S: Assessment of social adjustment by patient self-report. Arch Gen Psychiatry 33: 1111–1115, 1976

    PubMed  Google Scholar 

  37. Weissman MM, Pusoff BA, Thompson WD, Harding PS, Myers JK: Social adjustment by self-report in a community sample in psychiatric outpatients. J Nervous Mental Disease 166: 317–326, 1978

    Google Scholar 

  38. Heppner PP, Petersen CH: The development and implications of a personal problem-solving inventory. J Counseling Psychology 29: 66–75, 1982

    Google Scholar 

  39. Heppner PP, Baker CE: Assessment in action: Applications of the problem solving inventory. Measurement and evaluation in counseling and development 29: 229–241, 1997

    Google Scholar 

  40. Heppner PP: The problem solving inventory: manual. Consulting Psychologists Press, Palo Alto, CA, 1988, pp 5

    Google Scholar 

  41. Folstein MF, Folstein SE, McHugh PR: 'Mini-mental state'-A practical method for grading the cognitive state of patients for the clinician. J Psychiat Res 12: 189–198, 1975

    PubMed  Google Scholar 

  42. Kokmen E, Smith GE, Peterson RC, Tangalos E, Ivnik RC: The short test of mental status. Correlations with standardized psychometric testing. Arch Neurol 48: 725–728, 1991

    PubMed  Google Scholar 

  43. Packer RJ, Zimmerman RA, Bilaniuk LT: Magnetic resonance imaging in the evaluation of treatment-related central nervous system damage. Cancer 58: 635–640, 1986 268

    PubMed  Google Scholar 

  44. Allen JC, Rosen G, Mehta BM, Horten BH: Leukoencephalopathy following high-dose IV methotrexate chemotherapy with leucovorin rescue. Cancer Treat Rep 64: 1261–1273, 1980

    PubMed  Google Scholar 

  45. Skullerud K, Halvorsen K: Encephalomyelopathy following intrathecal methotrexate treatment in a child with acute leukemia; Cancer 42: 1211–1215, 1978

    PubMed  Google Scholar 

  46. Robinson JK, Boshier ML, Dansak DA, Peterson KJ: Depression and anxiety in cancer patients: Evidence for different causes. J Psychosomatic Res 29: 133–138, 1985

    Google Scholar 

  47. Crossen JR, Goldman D, Dahlborg SA, Neuwelt EA: Neuropsychological assessment outcomes of nonacquired immunodeficiency syndrome patients with primary central nervous system lymphoma before and after blood-brain barrier disruption chemotherapy. Neurosurgery 30: 23–29, 1992

    PubMed  Google Scholar 

  48. Kay HEM, Knapton PJ, O'Sullivan JP, Wells DG, Harris RF, Innes EM, Stuart J, Schwartz FCM, Thompson EN: Encephalopathy in acute leukemia associated with methotrexate therapy. Arch Disease in Childhood 47: 344–354, 1972

    Google Scholar 

  49. Kramer S: The hazards of therapeutic irradiation of the central nervous system. Clin Neurosurg 15: 301–318, 1968

    PubMed  Google Scholar 

  50. Chamberlain MC, Levin VA: Arch Neurol 47: 1113–1116, 1990

    PubMed  Google Scholar 

  51. Abrey LE, Yahalom J, DeAngelis LM: Relapse and late neurotoxicity in primary central nervous system lymphoma (PCNSL). (Abstracts) Neurology 48: A18, 1997

    Google Scholar 

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Guha-Thakurta, N., Damek, D., Pollack, C. et al. Intravenous Methotrexate as Initial Treatment for Primary Central Nervous System Lymphoma: Response to Therapy and Quality of Life of Patients. J Neurooncol 43, 259–268 (1999). https://doi.org/10.1023/A:1006210703827

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