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Nonpegylated liposomal doxorubicin is highly active in patients with B and T/NK cell lymphomas with cardiac comorbidity or higher age

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Abstract

We used nonpegylated liposomal doxorubicin (NPLD) in cytostatic drug combinations to treat 37 patients with non-Hodgkin's lymphoma and pre-existing cardiac disorder or elderly patients with reduced physical state who were ineligible for conventional anthracycline-containing therapy. High remission rates were observed in this poor-risk population: Complete remission rates were 75% for diffuse large B cell lymphoma (DLBCL) and 55% for T/NK cell neoplasm (overall response rate of 80% and 89%, respectively). Twenty-seven patients (73%) are still alive after a median observation time of 14 months. No major cardiac or gastrointestinal toxicity was observed. Extravasation of NPLD in two patients resulted in mild inflammation without tissue damage. Hematologic toxicity was comparable to that of conventional anthracycline-containing regimens. We conclude that NPLD is highly active in combination chemotherapy for lymphoma with low cardiac toxicity in patients with pre-existing cardiac disorders or higher age. Moreover, we also observed remarkable efficacy in T/NK cell lymphomas.

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References

  1. Armitage JO, Potter JF (1984) Aggressive chemotherapy for diffuse histiocytic lymphoma in the elderly: increased complications with advancing age. J Am Geriatr Soc 32:269–273

    CAS  PubMed  Google Scholar 

  2. Gomez H, Mas L, Casanova L et al (1998) Elderly patients with aggressive non-Hodgkin's lymphoma treated with CHOP chemotherapy plus granulocyte-macrophage colony-stimulating factor: identification of two age subgroups with differing hematologic toxicity. J Clin Oncol 16:2352–2358

    CAS  PubMed  Google Scholar 

  3. Peters FP, Lalisang RI, Fickers MM et al (2001) Treatment of elderly patients with intermediate- and high-grade non-Hodgkin's lymphoma: a retrospective population-based study. Ann Hematol 80:155–159

    Article  CAS  PubMed  Google Scholar 

  4. Salminen EK (1995) The outcome of > or =70-year-old non-Hodgkin's lymphoma patients. Int J Radiat Oncol Biol Phys 32:349–353

    Article  CAS  PubMed  Google Scholar 

  5. Tirelli U, Zagonel V, Serraino D et al (1988) Non-Hodgkin's lymphomas in 137 patients aged 70 years or older: a retrospective European Organization for Research and Treatment of Cancer Lymphoma Group study. J Clin Oncol 6:1708–1713

    CAS  PubMed  Google Scholar 

  6. Grann VR, Hershman D, Jacobson JS et al (2006) Outcomes and diffusion of doxorubicin-based chemotherapy among elderly patients with aggressive non-Hodgkin lymphoma. Cancer 107:1530–1541

    Article  CAS  PubMed  Google Scholar 

  7. Kouroukis CT, Browman GP, Esmail R et al (2002) Chemotherapy for older patients with newly diagnosed, advanced-stage, aggressive-histology non-Hodgkin lymphoma: a systematic review. Ann Intern Med 136:144–152

    CAS  PubMed  Google Scholar 

  8. Martelli M, Guglielmi C, Coluzzi S et al (1993) P-VABEC: a prospective study of a new weekly chemotherapy regimen for elderly aggressive non-Hodgkin's lymphoma. J Clin Oncol 11:2362–2369

    CAS  PubMed  Google Scholar 

  9. O'Reilly SE, Connors JM, Howdle S et al (1993) In search of an optimal regimen for elderly patients with advanced-stage diffuse large-cell lymphoma: results of a phase II study of P/DOCE chemotherapy. J Clin Oncol 11:2250–2257

    PubMed  Google Scholar 

  10. Sonneveld P, Michiels JJ (1990) Full dose chemotherapy in elderly patients with non-Hodgkin's lymphoma: a feasibility study using a mitoxantrone containing regimen. Br J Cancer 62:105–108

    CAS  PubMed  Google Scholar 

  11. Tirelli U, Zagonel V, Sorio R et al (1994) Mitoxantrone in combination with etoposide and prednimustine in patients older than 70 years with unfavorable non-Hodgkin's lymphoma: a prospective study in 52 patients. Semin Hematol 31:13–22

    CAS  PubMed  Google Scholar 

  12. Zinzani PL, Gherlinzoni F, Storti S et al (2002) Randomized trial of 8-week versus 12-week VNCOP-B plus G-CSF regimens as front-line treatment in elderly aggressive non-Hodgkin's lymphoma patients. Ann Oncol 13:1364–1369

    Article  CAS  PubMed  Google Scholar 

  13. Zinzani PL, Storti S, Zaccaria A et al (1999) Elderly aggressive-histology non-Hodgkin's lymphoma: first-line VNCOP-B regimen experience on 350 patients. Blood 94:33–38

    CAS  PubMed  Google Scholar 

  14. Singal PK, Iliskovic N (1998) Doxorubicin-induced cardiomyopathy. N Engl J Med 339:900–905

    Article  CAS  PubMed  Google Scholar 

  15. Von Hoff DD, Layard MW, Basa P et al (1979) Risk factors for doxorubicin-induced congestive heart failure. Ann Intern Med 91:710–717

    Google Scholar 

  16. Hequet O, Le QH, Moullet I et al (2004) Subclinical late cardiomyopathy after doxorubicin therapy for lymphoma in adults. J Clin Oncol 22:1864–1871

    Article  CAS  PubMed  Google Scholar 

  17. Limat S, Demesmay K, Voillat L et al (2003) Early cardiotoxicity of the CHOP regimen in aggressive non-Hodgkin's lymphoma. Ann Oncol 14:277–281

    Article  CAS  PubMed  Google Scholar 

  18. Hershman DL, McBride RB, Eisenberger A et al (2008) Doxorubicin, cardiac risk factors, and cardiac toxicity in elderly patients with diffuse B-cell non-Hodgkin's lymphoma. J Clin Oncol 26(19):3159–3165

    Article  CAS  PubMed  Google Scholar 

  19. Batist G, Barton J, Chaikin P et al (2002) Myocet (liposome-encapsulated doxorubicin citrate): a new approach in breast cancer therapy. Expert Opin Pharmacother 3(12):1739–1751

    Article  CAS  PubMed  Google Scholar 

  20. Chrischilles EA, Link BK, Scott SD et al (2003) Factors associated with early termination of CHOP therapy and the impact on survival among patients with chemosensitive intermediate-grade non-Hodgkin's lymphoma. Cancer Control 10:396–403

    PubMed  Google Scholar 

  21. Jensen BV, Skovsgaard T, Nielsen SL (2002) Functional monitoring of anthracycline cardiotoxicity: a prospective, blinded, long-term observational study of outcome in 120 patients. Ann Oncol 13(5):699–709

    Article  CAS  PubMed  Google Scholar 

  22. Hochster H, Liebes L, Wadler S et al (1992) Pharmacokinetics of the cardioprotector ADR-529 (ICRF-187) in escalating doses combined with fixed-dose doxorubicin. J Natl Cancer Inst 84(22):1725–1730

    Article  CAS  PubMed  Google Scholar 

  23. Swain SM, Whaley FS, Gerber MC et al (1997) Delayed administration of dexrazoxane provides cardioprotection for patients with advanced breast cancer treated with doxorubicin-containing therapy. J Clin Oncol 15:1333–1340

    CAS  PubMed  Google Scholar 

  24. Magnus B, Tomas A, Anders A et al (2008) CNOP (mitoxantrone) chemotherapy is inferior to CHOP (doxorubicin) in the treatment of patients with aggressive non-Hodgkin lymphoma (meta-analysis). Eur J Haematol 80(6):477–482

    Article  CAS  PubMed  Google Scholar 

  25. Nakamae H, Tsumura K, Terada Y et al (2005) Notable effects of angiotensin II receptor blocker, valsartan, on acute cardiotoxic changes after standard chemotherapy with cyclophosphamide, doxorubicin, vincristine, and prednisolone. Cancer 104:2492–2498

    Article  CAS  PubMed  Google Scholar 

  26. Zaja F, Tomadini V, Zaccaria A et al (2006) CHOP-rituximab with pegylated liposomal doxorubicin for the treatment of elderly patients with diffuse large B-cell lymphoma. Leuk Lymphoma 47:2174–2180

    Article  CAS  PubMed  Google Scholar 

  27. Tsavaris N, Kosmas C, Vadiaka M et al (2002) Pegylated liposomal doxorubicin in the CHOP regimen for older patients with aggressive (stages III/IV) non-Hodgkin's lymphoma. Anticancer Res 22:1845–1848

    CAS  PubMed  Google Scholar 

  28. Visani G, Isidori A (2009) Nonpegylated liposomal doxorubicin in the treatment of B-cell non-Hodgkins lymphoma: where we stand. Expert Rev Anticancer Ther 9(3):357–363

    Article  CAS  PubMed  Google Scholar 

  29. Rigacci L, Mappa S, Nassi L et al (2007) Liposome-encapsulated doxorubicin in combination with cyclophosphamide, vincristine, prednisone and rituximab in patients with lymphoma and concurrent cardiac diseases or pre-treated with anthracyclines. Hematol Oncol 25:198–203

    Article  CAS  PubMed  Google Scholar 

  30. Visani G, Ferrara F, Alesiani F et al (2008) R-COMP 21 for frail elderly patients with aggressive B-cell non-Hodgkin lymphom a: a pilot study. Leuk Lymphoma 49(6):1081–1086

    Article  CAS  PubMed  Google Scholar 

  31. de Leval L, Gaulard P (2008) Pathobiology and molecular profiling of peripheral T-cell lymphomas. Hematology Am Soc Hematol Educ Program 2008:272–279

    Google Scholar 

  32. Savage K (2008) Prognosis and primary therapy in peripheral T-cell lymphomas. Hematology Am Soc Hematol Educ Program 2008:280–288

    Google Scholar 

  33. Schützinger C, Esterbauer H, Hron G et al (2008) Prognostic value of T-cell receptor γ rearrangement in peripheral blood or bone marrow of patients with peripheral T-cell lymphomas. Leuk Lymphoma 49(2):237–246

    Article  PubMed  Google Scholar 

  34. Armitage J, Vose J, Weisenburger D et al (2008) International Peripheral T-Cell and Natural Killer/T-Cell Lymphoma Study: pathophysiology findings and clinical outcomes. J Clin Oncol 26(25):4124–4130

    Article  PubMed  Google Scholar 

  35. Horwitz S (2008) Novel therapies and role of transplant in the treatment of peripheral T-cell lymphomas. Hematology Am Soc Hematol Educ Program 2008:289–296

    Google Scholar 

  36. Pro B, Fayad L, Romaguera J et al (2007) Preliminary results of a phase II study of HCVlDDoxil alternated with methotrexate-cytarabine in patients with newly diagnosed T-cell lymphoma. Blood 110 (abstract #3456)

  37. Swerdlow SH, Campo E, Harris NL et al (2008) WHO classification of tumours of haematopoietic and lymphoid tissues, 4th edn. International Agency for Research on Cancer, Lyon

    Google Scholar 

  38. Cheson BD (2008) New response criteria for lymphomas in clinical trials. Ann Oncol 19(4):35–38

    Article  Google Scholar 

  39. Tulpule A, Espina BM, Berman N et al (2006) Phase I/II trial of nonpegylated liposomal doxorubicin, cyclophosphamide, vincristine, and prednisone in the treatment of newly diagnosed aggressive non-Hodgkin's lymphoma. Clin Lymphoma Myeloma 7(1):59–64

    Article  CAS  PubMed  Google Scholar 

  40. Cortes J, DiCosimo S, Climent MA et al (2009) Nonpegylated liposomal doxorubicin (TLC-D99), paclitaxel, and trastuzumab in HER-2-overexpressing breast cancer: a multicenter phase I/II study. Clin Cancer Res 15(1):307–314

    Article  CAS  PubMed  Google Scholar 

  41. Weber M, Hamm C (2006) Role of B-type natriuretic peptide (BNP) and NT-proBNP in clinical routine. Heart 92(6):843–849

    Article  CAS  PubMed  Google Scholar 

  42. Doust JA, Glasziou PP, Pietrzak E et al (2004) Systematic review of the diagnostic accuracy of natriuretic peptides for heart failure. Arch Intern Med 164:1978–1984

    Article  CAS  PubMed  Google Scholar 

  43. Perik PJ, De Vries EG, Boomsma F et al (2005) Use of natriuretic peptides for detecting cardiac dysfunction in long-term disease-free breast cancer survivors. Anticancer Res 25(5):3651–3657

    CAS  PubMed  Google Scholar 

  44. Daugaard G, Lassen U, Bie P et al (2005) Natriuretic peptides in the monitoring of anthracycline induced reduction in left ventricular ejection fraction. Eur J Heart Fail 7(5):940–941

    Article  Google Scholar 

  45. Meinardi MT, Van Veldhuisen DJ, Gietema JA et al (2001) Prospective evaluation of early cardiac damage induced by epirubicin-containing adjuvant chemotherapy and locoregional radiotherapy in breast cancer patients. J Clin Oncol 19:2746–2753

    CAS  PubMed  Google Scholar 

  46. Nousiainen T, Vanninen E, Jantunen E et al (2002) Natriuretic peptides during the development of doxorubicin-induced left ventricular diastolic dysfunction. J Intern Med 251(3):228–234

    Article  CAS  PubMed  Google Scholar 

  47. Rudolph R, Stein SR, Patillo RA (1976) Skin ulcers due to adriamycin. Cancer 38:1087–1094

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Internal Medicine I, Division of Hematology and Hemostaseology, Medical University of Vienna, Währinger Gürtel 18–20, 1090, Vienna, Austria

    Daniel Heintel, Cathrin Skrabs, Alexander Hauswirth, Karin Eigenberger, Christine Einberger, Wolfgang R. Sperr, Paul Knöbl, Alexander Gaiger & Ulrich Jäger

  2. Department of Internal Medicine I, Division of Clinical Oncology, Medical University of Vienna, Vienna, Austria

    Markus Raderer

  3. Department of Clinical Pathology, Medical University of Vienna, Vienna, Austria

    Leonhard Müllauer

  4. Department of Radiotherapy and Radiobiology, Medical University of Vienna, Vienna, Austria

    Martin Uffmann & Karin Dieckmann

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  1. Daniel Heintel
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Correspondence to Ulrich Jäger.

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Heintel, D., Skrabs, C., Hauswirth, A. et al. Nonpegylated liposomal doxorubicin is highly active in patients with B and T/NK cell lymphomas with cardiac comorbidity or higher age. Ann Hematol 89, 163–169 (2010). https://doi.org/10.1007/s00277-009-0796-5

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