The more patients you treat, the more you cure: managing cardiotoxicity in the treatment of aggressive non-Hodgkin lymphoma

Abstract Athracycline-based regimens remain the gold standard for the treatment of lymphomas, even if their use can be limited by associated cardiac toxicity, especially in elderly patients. Although most patients with aggressive non-Hodgkin lymphoma (NHL) are elderly, they may envisage long-term life expectancy. Thus, there is a need for therapeutic strategies that can overcome the impact of anthracycline cardiotoxicity. A better understanding of its pathogenetic mechanisms, the identification of risk factors of cardiac dysfunction, and appropriate therapy should prove useful in this setting. A comparable efficacy and reduced cardiotoxicity even in frail and elderly patients have been shown with the use of non-pegylated liposomal doxorubicin, when substituted for conventional doxorubicin in standard chemotherapy regimens for NHL. In the coming years, the goal will be to apply these advancements to the treatment of patients with NHL, to ensure adequate therapy in patients currently denied conventional intensive chemotherapy because of age or comorbidities.

[1]  J. Singer,et al.  Comparison of pixantrone-based regimen (CPOP-R) with doxorubicin-based therapy (CHOP-R) for treatment of diffuse large B-cell lymphoma. , 2013, Annals of oncology : official journal of the European Society for Medical Oncology.

[2]  J. Singer,et al.  The Novel Anthracenedione, Pixantrone, Lacks Redox Activity and Inhibits Doxorubicinol Formation in Human Myocardium: Insight to Explain the Cardiac Safety of Pixantrone in Doxorubicin-Treated Patients , 2013, The Journal of Pharmacology and Experimental Therapeutics.

[3]  A. Rosenwald,et al.  Conventional chemotherapy (CHOEP-14) with rituximab or high-dose chemotherapy (MegaCHOEP) with rituximab for young, high-risk patients with aggressive B-cell lymphoma: an open-label, randomised, phase 3 trial (DSHNHL 2002-1). , 2012, The Lancet. Oncology.

[4]  M. Weichenthal,et al.  Prospective international multicenter phase II trial of intravenous pegylated liposomal doxorubicin monochemotherapy in patients with stage IIB, IVA, or IVB advanced mycosis fungoides: final results from EORTC 21012. , 2012, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[5]  A. Goldhirsch,et al.  Cardiovascular toxicity induced by chemotherapy, targeted agents and radiotherapy: ESMO Clinical Practice Guidelines. , 2012, Annals of oncology : official journal of the European Society for Medical Oncology.

[6]  L. Castellano,et al.  Breast Cancer Treatment and Adverse Cardiac Events: What Are the Molecular Mechanisms? , 2012, Cardiology.

[7]  B. Coiffier,et al.  Pixantrone dimaleate versus other chemotherapeutic agents as a single-agent salvage treatment in patients with relapsed or refractory aggressive non-Hodgkin lymphoma: a phase 3, multicentre, open-label, randomised trial. , 2012, The Lancet. Oncology.

[8]  H. Crijns,et al.  Doxorubicin-induced cardiomyopathy: from molecular mechanisms to therapeutic strategies. , 2012, Journal of molecular and cellular cardiology.

[9]  M. Relling,et al.  Anthracycline-related cardiomyopathy after childhood cancer: role of polymorphisms in carbonyl reductase genes--a report from the Children's Oncology Group. , 2012, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[10]  M. Hayden,et al.  Pharmacogenomic prediction of anthracycline-induced cardiotoxicity in children. , 2012, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[11]  D. Linch,et al.  Treatment of the elderly patient with diffuse large B cell lymphoma , 2012, British journal of haematology.

[12]  P. Mazza,et al.  Cyclophosphamide, doxorubicin, vincristine, prednisone and rituximab versus epirubicin, cyclophosphamide, vinblastine, prednisone and rituximab for the initial treatment of elderly “fit” patients with diffuse large B-cell lymphoma: results from the ANZINTER3 trial of the Intergruppo Italiano Linfomi , 2012, Leukemia & lymphoma.

[13]  H. Shmeeda,et al.  Pharmacological basis of pegylated liposomal doxorubicin: impact on cancer therapy. , 2012, European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences.

[14]  C. Kramer,et al.  Non-invasive imaging and monitoring cardiotoxicity of cancer therapeutic drugs , 2012, Journal of Nuclear Cardiology.

[15]  M. Janssen-Heijnen,et al.  Diverging trends in incidence and mortality, and improved survival of non-Hodgkin's lymphoma, in the Netherlands, 1989-2007. , 2012, Annals of oncology : official journal of the European Society for Medical Oncology.

[16]  S. Dietrich,et al.  Replacement of conventional doxorubicin by pegylated liposomal doxorubicin is a safe and effective alternative in the treatment of non-Hodgkin's lymphoma patients with cardiac risk factors , 2012, Annals of Hematology.

[17]  S. Choe,et al.  Addition of rituximab to reduced-dose CHOP chemotherapy is feasible for elderly patients with diffuse large B-cell lymphoma , 2012, Cancer Chemotherapy and Pharmacology.

[18]  T. Molina,et al.  Intensified chemotherapy with ACVBP plus rituximab versus standard CHOP plus rituximab for the treatment of diffuse large B-cell lymphoma (LNH03-2B): an open-label randomised phase 3 trial , 2011, The Lancet.

[19]  M. Federico,et al.  Anthracyclines: a cornerstone in the management of non-Hodgkin's lymphoma , 2011, Hematology reports.

[20]  A. López-Guillermo,et al.  CHOP-like chemotherapy with or without rituximab in young patients with good-prognosis diffuse large-B-cell lymphoma: 6-year results of an open-label randomised study of the MabThera International Trial (MInT) Group. , 2011, The Lancet. Oncology.

[21]  F. Russo,et al.  Biweekly rituximab, cyclophosphamide, vincristine, non-pegylated liposome-encapsulated doxorubicin and prednisone (R-COMP-14) in elderly patients with poor-risk diffuse large B-cell lymphoma and moderate to high ‘life threat’ impact cardiopathy , 2011, British journal of haematology.

[22]  A. la Sala,et al.  Non-pegylated liposomal doxorubicin (Myocet®) in patients with poor-risk aggressive B-cell non-Hodgkin lymphoma , 2011, Leukemia & lymphoma.

[23]  H. Dickinson,et al.  Cardioprotective interventions for cancer patients receiving anthracyclines. , 2011, The Cochrane database of systematic reviews.

[24]  F. Jardin,et al.  Attenuated immunochemotherapy regimen (R-miniCHOP) in elderly patients older than 80 years with diffuse large B-cell lymphoma: a multicentre, single-arm, phase 2 trial. , 2011, The Lancet. Oncology.

[25]  J. Singer,et al.  Phase I/II study of pixantrone in combination with cyclophosphamide, vincristine, and prednisone in patients with relapsed aggressive non-Hodgkin lymphoma , 2011, Leukemia & lymphoma.

[26]  Takeshi Takahashi,et al.  Phase II study of the tetrahydropyranyl adriamycin–cyclophosphamide, vincristine, and prednisolone regimen combined with rituximab as first-line treatment for elderly patients with diffuse large B-cell lymphoma , 2011, Leukemia & lymphoma.

[27]  A. Salar,et al.  Intermediate dose of nonpegylated liposomal doxorubicin combination (R-CMyOP) as first line chemotherapy for frail elderly patients with aggressive lymphoma. , 2011, Leukemia research.

[28]  M. Aapro,et al.  Anthracycline cardiotoxicity in the elderly cancer patient: a SIOG expert position paper. , 2011, Annals of oncology : official journal of the European Society for Medical Oncology.

[29]  C. Pafumi,et al.  The reproduction in women affected by cooley disease , 2011, Hematology reports.

[30]  B. Leikind,et al.  An Assessment of , 2011 .

[31]  J. Briones,et al.  Nonpegylated liposomal doxorubicin (MyocetTM) combination (R-COMP) chemotherapy in elderly patients with diffuse large B-cell lymphoma (DLBCL): results from the phase II EUR018 trial. , 2010, Annals of oncology : official journal of the European Society for Medical Oncology.

[32]  V. Cornelius,et al.  Cardiotoxicity of anthracycline agents for the treatment of cancer: Systematic review and meta-analysis of randomised controlled trials , 2010, BMC Cancer.

[33]  F. Roila,et al.  Cardiotoxicity of chemotherapeutic agents and radiotherapy-related heart disease: ESMO Clinical Practice Guidelines. , 2010, Annals of oncology : official journal of the European Society for Medical Oncology.

[34]  F. Veglia,et al.  Anthracycline-induced cardiomyopathy: clinical relevance and response to pharmacologic therapy. , 2010, Journal of the American College of Cardiology.

[35]  H. Caron,et al.  Different anthracycline derivates for reducing cardiotoxicity in cancer patients. , 2010, The Cochrane database of systematic reviews.

[36]  M. Uffmann,et al.  Nonpegylated liposomal doxorubicin is highly active in patients with B and T/NK cell lymphomas with cardiac comorbidity or higher age , 2010, Annals of Hematology.

[37]  H. Caron,et al.  Different dosage schedules for reducing cardiotoxicity in cancer patients receiving anthracycline chemotherapy. , 2009, The Cochrane database of systematic reviews.

[38]  A. Levis,et al.  Dose-dense and high-dose chemotherapy plus rituximab with autologous stem cell transplantation for primary treatment of diffuse large B-cell lymphoma with a poor prognosis: a phase II multicenter study , 2009, Haematologica.

[39]  B. Malmer,et al.  Long‐term risk of cardiovascular disease in Hodgkin lymphoma survivors—Retrospective cohort analyses and a concept for prospective intervention , 2009, International journal of cancer.

[40]  E. D. de Vries,et al.  Cardiovascular toxicity caused by cancer treatment: strategies for early detection. , 2009, The Lancet. Oncology.

[41]  G. Visani,et al.  Nonpegylated liposomal doxorubicin in the treatment of B-cell non-Hodgkin’s lymphoma: where we stand , 2009, Expert review of anticancer therapy.

[42]  W. Gradishar,et al.  American Society of Clinical Oncology 2008 clinical practice guideline update: use of chemotherapy and radiation therapy protectants. , 2009, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[43]  C. Palmieri,et al.  Efficacy and toxicity of nonpegylated liposomal doxorubicin in breast cancer , 2008, Expert review of anticancer therapy.

[44]  Robin L. Jones Utility of dexrazoxane for the reduction of anthracycline-induced cardiotoxicity , 2008, Expert review of cardiovascular therapy.

[45]  Narine Sarvazyan,et al.  Anthracycline cardiotoxicity: from bench to bedside. , 2008, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[46]  W. Tsai,et al.  Doxorubicin, cardiac risk factors, and cardiac toxicity in elderly patients with diffuse B-cell non-Hodgkin's lymphoma. , 2008, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[47]  J. Glick,et al.  Doxorubicin cardiotoxicity in the elderly: old drugs and new opportunities. , 2008, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[48]  J. Horáček,et al.  Monitoring of the very early changes of left ventricular diastolic function in patients with acute leukemia treated with anthracyclines. , 2008, Experimental oncology.

[49]  H. Harputluoglu,et al.  Addition of rituximab to chop does not increase the risk of cardiotoxicity in patients with non-Hodgkin’s lymphoma , 2008, Medical oncology.

[50]  A. Gabizon,et al.  Clinical pharmacology of liposomal anthracyclines: focus on pegylated liposomal Doxorubicin. , 2008, Clinical lymphoma & myeloma.

[51]  Markus Loeffler,et al.  Six versus eight cycles of bi-weekly CHOP-14 with or without rituximab in elderly patients with aggressive CD20+ B-cell lymphomas: a randomised controlled trial (RICOVER-60). , 2008, The Lancet. Oncology.

[52]  F. Alesiani,et al.  R-COMP 21 for frail elderly patients with aggressive B-cell non-Hodgkin lymphoma: A pilot study , 2008, Leukemia & lymphoma.

[53]  J. D’hooge,et al.  Detection and monitoring of cardiotoxicity—what does modern cardiology offer? , 2008, Supportive Care in Cancer.

[54]  E. Erdmann,et al.  Usefulness of myocardial performance index and biochemical markers for early detection of anthracycline-induced cardiotoxicity in adults , 2008, Clinical Research in Cardiology.

[55]  A. Bosi,et al.  Liposome‐encapsulated doxorubicin in combination with cyclophosphamide, vincristine, prednisone and rituximab in patients with lymphoma and concurrent cardiac diseases or pre‐treated with anthracyclines , 2007, Hematological oncology.

[56]  J. Horáček,et al.  Assessment of anthracycline-induced cardiotoxicity with biochemical markers. , 2007, Experimental oncology.

[57]  T. Merchant,et al.  Noninvasive evaluation of late anthracycline cardiac toxicity in childhood cancer survivors. , 2007, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[58]  S. Lipshultz,et al.  Anthracycline-induced cardiotoxicity: course, pathophysiology, prevention and management , 2007, Expert opinion on pharmacotherapy.

[59]  L. Wojnowski,et al.  Genotyping the risk of anthracycline-induced cardiotoxicity , 2007, Cardiovascular Toxicology.

[60]  S. Lipshultz,et al.  Anthracycline cardiotoxicity in long-term survivors of childhood cancer , 2007, Cardiovascular Toxicology.

[61]  G. Takemura,et al.  Doxorubicin-induced cardiomyopathy from the cardiotoxic mechanisms to management. , 2007, Progress in cardiovascular diseases.

[62]  A. Tulpule,et al.  A phase I/II trial of pixantrone (BBR2778), methylprednisolone, cisplatin, and cytosine arabinoside (PSHAP) in relapsed/refractory aggressive non-Hodgkin's lymphoma , 2007, Leukemia & lymphoma.

[63]  Giovanni Martinelli,et al.  Prevention of High-Dose Chemotherapy-Induced Cardiotoxicity in High-Risk Patients by Angiotensin-Converting Enzyme Inhibition , 2006, Circulation.

[64]  A. Dogan,et al.  Protective effects of carvedilol against anthracycline-induced cardiomyopathy. , 2006, Journal of the American College of Cardiology.

[65]  Kevin C Oeffinger,et al.  Chronic health conditions in adult survivors of childhood cancer. , 2006, The New England journal of medicine.

[66]  B. Nathwani,et al.  Phase I/II trial of nonpegylated liposomal doxorubicin, cyclophosphamide, vincristine, and prednisone in the treatment of newly diagnosed aggressive non-Hodgkin's lymphoma. , 2006, Clinical lymphoma & myeloma.

[67]  G. Batist,et al.  Improved anti-tumor response rate with decreased cardiotoxicity of non-pegylated liposomal doxorubicin compared with conventional doxorubicin in first-line treatment of metastatic breast cancer in patients who had received prior adjuvant doxorubicin: results of a retrospective analysis , 2006, Anti-cancer drugs.

[68]  S. Johnson Anthracycline-induced cardiotoxicity in adult hematologic malignancies. , 2006, Seminars in oncology.

[69]  A. López-Guillermo,et al.  CHOP-like chemotherapy plus rituximab versus CHOP-like chemotherapy alone in young patients with good-prognosis diffuse large-B-cell lymphoma: a randomised controlled trial by the MabThera International Trial (MInT) Group. , 2006, The Lancet. Oncology.

[70]  R. Fanin,et al.  CHOP-rituximab with pegylated liposomal doxorubicin for the treatment of elderly patients with diffuse large B-cell lymphoma , 2006, Leukemia & lymphoma.

[71]  M. Pfreundschuh,et al.  NAD(P)H Oxidase and Multidrug Resistance Protein Genetic Polymorphisms Are Associated With Doxorubicin-Induced Cardiotoxicity , 2005, Circulation.

[72]  S. Radulović,et al.  Activity of d,l-alpha-tocopherol (vitamin E) against cardiotoxicity induced by doxorubicin and doxorubicin with cyclophosphamide in mice. , 2005, Basic & clinical pharmacology & toxicology.

[73]  R. Gascoyne,et al.  Introduction of combined CHOP plus rituximab therapy dramatically improved outcome of diffuse large B-cell lymphoma in British Columbia. , 2005, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[74]  C. Burton,et al.  Comparison of CHOP versus CIOP in good prognosis younger patients with histologically aggressive non‐Hodgkin lymphoma , 2005, British journal of haematology.

[75]  P. Gaulard,et al.  Long-term results of the R-CHOP study in the treatment of elderly patients with diffuse large B-cell lymphoma: a study by the Groupe d'Etude des Lymphomes de l'Adulte. , 2005, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[76]  E. Hayek,et al.  Acute doxorubicin cardiotoxicity. , 2005, The New England journal of medicine.

[77]  S. Lipsitz,et al.  Chronic progressive cardiac dysfunction years after doxorubicin therapy for childhood acute lymphoblastic leukemia. , 2005, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[78]  T. Molina,et al.  ACVBP versus CHOP plus radiotherapy for localized aggressive lymphoma. , 2005, The New England journal of medicine.

[79]  Theresa M Allen,et al.  Advantages of liposomal delivery systems for anthracyclines. , 2004, Seminars in oncology.

[80]  S. Chan,et al.  Phase III trial of liposomal doxorubicin and cyclophosphamide compared with epirubicin and cyclophosphamide as first-line therapy for metastatic breast cancer. , 2004, Annals of oncology : official journal of the European Society for Medical Oncology.

[81]  Dirk Hasenclever,et al.  Two-weekly or 3-weekly CHOP chemotherapy with or without etoposide for the treatment of young patients with good-prognosis (normal LDH) aggressive lymphomas: results of the NHL-B1 trial of the DSHNHL. , 2004, Blood.

[82]  Dirk Hasenclever,et al.  Two-weekly or 3-weekly CHOP chemotherapy with or without etoposide for the treatment of elderly patients with aggressive lymphomas: results of the NHL-B2 trial of the DSHNHL. , 2004, Blood.

[83]  G. Martinelli,et al.  Prognostic Value of Troponin I in Cardiac Risk Stratification of Cancer Patients Undergoing High-Dose Chemotherapy , 2004, Circulation.

[84]  G. Salles,et al.  Subclinical late cardiomyopathy after doxorubicin therapy for lymphoma in adults. , 2004, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[85]  B. Conley,et al.  Phase I and pharmacokinetic trial of liposome-encapsulated doxorubicin , 2004, Cancer Chemotherapy and Pharmacology.

[86]  P. Sonneveld,et al.  CHOP compared with CHOP plus granulocyte colony-stimulating factor in elderly patients with aggressive non-Hodgkin's lymphoma. , 2003, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[87]  R. Fisher,et al.  Dose-intense chemotherapy every 2 weeks with dose-intense cyclophosphamide, doxorubicin, vincristine, and prednisone may improve survival in intermediate- and high-grade lymphoma: a phase II study of the Southwest Oncology Group (SWOG 9349). , 2003, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[88]  S. Swain,et al.  Congestive heart failure in patients treated with doxorubicin , 2003, Cancer.

[89]  S. Chow,et al.  Pharmacokinetics of doxorubicin administered i.v. as Myocet (TLC D-99; liposome-encapsulated doxorubicin citrate) compared with conventional doxorubicin when given in combination with cyclophosphamide in patients with metastatic breast cancer , 2003, Anti-cancer drugs.

[90]  E. Deconinck,et al.  Early cardiotoxicity of the CHOP regimen in aggressive non-Hodgkin's lymphoma. , 2003, Annals of oncology : official journal of the European Society for Medical Oncology.

[91]  C. Gisselbrecht,et al.  Phase-II study of the new aza-anthracenedione, BBR 2778, in patients with relapsed aggressive non-Hodgkin's lymphomas. , 2003, Haematologica.

[92]  P. Vici,et al.  The current and future role of dexrazoxane as a cardioprotectant in anthracycline treatment: expert panel review , 2003, Journal of Cancer Research and Clinical Oncology.

[93]  B. E. C. Oiffier,et al.  CHOP Chemotherapy plus Rituximab Compared with CHOP Alone in Elderly Patients with Diffuse Large-B-Cell Lymphoma , 2002 .

[94]  M. Terol,et al.  vincristine and prednisone (CCOP) in elderly patients with diffuse large B-cell lymphoma: results from a prospective phase II study , 2002 .

[95]  Lyndsay Harris,et al.  Liposome‐encapsulated doxorubicin compared with conventional doxorubicin in a randomized multicenter trial as first‐line therapy of metastatic breast carcinoma , 2002, Cancer.

[96]  A. Avilés,et al.  Pegylated liposomal doxorubicin in combination chemotherapy in the treatment of previously untreated aggressive diffuse large-B-cell lymphoma , 2002, Medical oncology.

[97]  M. Terol,et al.  Cyclophosphamide, pegylated liposomal doxorubicin (Caelyx), vincristine and prednisone (CCOP) in elderly patients with diffuse large B-cell lymphoma: results from a prospective phase II study. , 2002, Haematologica.

[98]  V. Diehl,et al.  Phase I study of BBR 2778, a new aza-anthracenedione, in advanced or refractory non-Hodgkin's lymphoma. , 2001, Annals of oncology : official journal of the European Society for Medical Oncology.

[99]  P. Whelton,et al.  Risk factors for congestive heart failure in US men and women: NHANES I epidemiologic follow-up study. , 2001, Archives of internal medicine.

[100]  G. Batist,et al.  Reduced cardiotoxicity and preserved antitumor efficacy of liposome-encapsulated doxorubicin and cyclophosphamide compared with conventional doxorubicin and cyclophosphamide in a randomized, multicenter trial of metastatic breast cancer. , 2001, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[101]  E. Noordijk,et al.  Different age limits for elderly patients with indolent and aggressive non‐Hodgkin lymphoma and the role of relative survival with increasing age , 2000, Cancer.

[102]  M. Runge,et al.  Doxorubicin-Induced Cardiomyopathy , 2000 .

[103]  G. Hortobagyi,et al.  Phase II trial of liposome-encapsulated doxorubicin, cyclophosphamide, and fluorouracil as first-line therapy in patients with metastatic breast cancer. , 1999, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[104]  J. Blay,et al.  Elderly patients with aggressive non-Hodgkin's lymphoma: disease presentation, response to treatment, and survival--a Groupe d'Etude des Lymphomes de l'Adulte study on 453 patients older than 69 years. , 1997, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[105]  A. Levis,et al.  The treatment of elderly patients with aggressive non-Hodgkin's lymphomas: feasibility and efficacy of an intensive multidrug regimen. , 1996, Leukemia & lymphoma.

[106]  W Hop,et al.  Comparison of doxorubicin and mitoxantrone in the treatment of elderly patients with advanced diffuse non-Hodgkin's lymphoma using CHOP versus CNOP chemotherapy. , 1995, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[107]  E. Iannitto,et al.  Phase III comparative trial using CHOP vs CIOP in the treatment of advanced intermediate-grade non-Hodgkin's lymphoma. , 1995, Leukemia & lymphoma.

[108]  E J Orav,et al.  Female sex and higher drug dose as risk factors for late cardiotoxic effects of doxorubicin therapy for childhood cancer. , 1995, The New England journal of medicine.

[109]  A. Ho,et al.  Long-term results of a multicentre randomised, comparative phase III trial of CHOP versus CNOP regimens in patients with intermediate-and high-grade non-Hodgkin's lymphomas , 1995 .

[110]  H. Niitani,et al.  [Phase II study]. , 1995, Gan to kagaku ryoho. Cancer & chemotherapy.

[111]  W. Bezwoda,et al.  Long-term results of a multicentre randomised, comparative phase III trial of CHOP versus CNOP regimens in patients with intermediate- and high-grade non-Hodgkin's lymphomas. Novantrone International Study Group. , 1995, European Journal of Cancer.

[112]  J. Graham-Pole,et al.  Phase II Trial , 1994, Annals of Internal Medicine.

[113]  D. Marchant,et al.  Risk factors. , 1994, Obstetrics and gynecology clinics of North America.

[114]  N. Petrelli,et al.  Initial clinical (phase I) trial of TLC D-99 (doxorubicin encapsulated in liposomes). , 1993, Cancer research.

[115]  T M Grogan,et al.  Comparison of a standard regimen (CHOP) with three intensive chemotherapy regimens for advanced non-Hodgkin's lymphoma. , 1993, The New England journal of medicine.

[116]  A Dritschilo,et al.  Modulation of doxorubicin resistance in multidrug‐resistant cells by liposomes , 1993, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[117]  Z. Pavelic,et al.  Comparison of the cardiotoxic effects of liposomal doxorubicin (TLC D-99) versus free doxorubicin in beagle dogs. , 1993, In vivo.

[118]  A. Erazo,et al.  Results of a randomized study of previously-untreated intermediate and high grade lymphoma using CHOP versus CNOP. , 1992, Annals of oncology : official journal of the European Society for Medical Oncology.

[119]  M. Bally,et al.  Comparison of free and liposome encapsulated doxorubicin tumor drug uptake and antitumor efficacy in the SC115 murine mammary tumor. , 1990, Cancer letters.

[120]  M. Rich,et al.  Reversibility of severe left ventricular dysfunction due to doxorubicin cardiotoxicity. Report of three cases. , 1987, Annals of internal medicine.

[121]  T. Miller,et al.  Effect of age on therapeutic outcome in advanced diffuse histiocytic lymphoma: the Southwest Oncology Group experience. , 1986, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[122]  J. Cerhan,et al.  HEMATOLOGIC MALIGNANCIES , 2007, UICC Current Treatment of Cancer.

[123]  R. Scott,et al.  Long-Term Results , 2001 .

[124]  M. Cohen,et al.  Reversible doxorubicin-induced congestive heart failure. , 1982, Archives of internal medicine.

[125]  D. V. Von Hoff,et al.  Risk factors for doxorubicin-induced congestive heart failure. , 1979, Annals of internal medicine.

[126]  E. Frei,et al.  Chemotherapy of malignant lymphoma with adriamycin. , 1973, Cancer research.

[127]  W. J. Hadden,et al.  A Comparison of , 1971 .

[128]  J. J. Buckley,et al.  Report of Three Cases , 1962 .