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Metronomic Chemotherapy in Hematological Malignancies

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Metronomic Chemotherapy

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Abstract

Targeting tumor microenvironment and angiogenesis is a novel therapeutic strategy in hematological malignancies. The antiangiogenic effects of chemotherapeutic agents can be optimized when administered metronomically, by providing low doses of chemotherapeutic drugs on a continuous schedule without extended drug-free intervals. Metronomic chemotherapy preferentially targets endothelial cells of the growing tumor neovasculature instead of tumor cells themselves and therefore can be particularly effective against multidrug-resistant tumors. Metronomic therapy may further enhance immune response by modulating antitumor NK/T-cell functions. The past decade saw an increasing appreciation of the pathogenic roles that tumor angiogenesis plays in hematological malignancies including leukemias, lymphomas, and multiple myeloma. Experimentation with a variety of antiangiogenesis modalities has shown encouraging efficacy with metronomic chemotherapy in these disease categories, with generally low toxicity and cost. With the growing availability of the target-specific biological agents, some of which are specific for antiangiogenesis, it is conceivable that metronomic chemotherapy, either alone or in combination with biologics, has therapeutic potential in frontline and maintenance setting, in addition to its traditional role of salvage option for relapsed diseases in hematological malignancies.

Financial Disclosure

J. R. has received research support from Celgene, Seattle Genetics, and Millennium.

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References

  1. Kerbel RS, Kamen BA (2004) The anti-angiogenic basis of metronomic chemotherapy. Nat Rev Cancer 4(6):423–436

    Article  CAS  PubMed  Google Scholar 

  2. Ferrara N, Kerbel RS (2005) Angiogenesis as a therapeutic target. Nature 438(7070):967–974

    Article  CAS  PubMed  Google Scholar 

  3. Shaked Y, Bertolini F, Emmenegger U, Lee CR, Kerbel RS (2006) On the origin and nature of elevated levels of circulating endothelial cells after treatment with a vascular disrupting agent. J Clin Oncol 24(24):4040; author reply 4040–4041

    Article  PubMed  Google Scholar 

  4. Shaked Y, Emmenegger U, Francia G, Chen L, Lee CR, Man S, Paraghamian A, Ben-David Y, Kerbel RS (2005) Low-dose metronomic combined with intermittent bolus-dose cyclophosphamide is an effective long-term chemotherapy treatment strategy. Cancer Res 65(16):7045–7051

    Article  CAS  PubMed  Google Scholar 

  5. Browder T, Butterfield CE, Kräling BM, Shi B, Marshall B, O’Reilly MS, Folkman J (2000) Antiangiogenic scheduling of chemotherapy improves efficacy against experimental drug-resistant cancer. Cancer Res 60(7):1878–1886

    CAS  PubMed  Google Scholar 

  6. Bocci G, Nicolaou KC, Kerbel RS (2002) Protracted low-dose effects on human endothelial cell proliferation and survival in vitro reveal a selective antiangiogenic window for various chemotherapeutic drugs. Cancer Res 62(23):6938–6943

    CAS  PubMed  Google Scholar 

  7. Bocci G, Francia G, Man S, Lawler J, Kerbel RS (2003) Thrombospondin 1, a mediator of the antiangiogenic effects of low-dose metronomic chemotherapy. Proc Natl Acad Sci U S A 100(22):12917–12922

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  8. Bertolini F, Paul S, Mancuso P, Monestiroli S, Gobbi A, Shaked Y, Kerbel RS (2003) Maximum tolerable dose and low-dose metronomic chemotherapy have opposite effects on the mobilization and viability of circulating endothelial progenitor cells. Cancer Res 63(15):4342–4346

    CAS  PubMed  Google Scholar 

  9. Shaked Y, Emmenegger U, Man S, Cervi D, Bertolini F, Ben-David Y, Kerbel RS (2005) Optimal biologic dose of metronomic chemotherapy regimens is associated with maximum antiangiogenic activity. Blood 106(9):3058–3061

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  10. Le DT, Jaffee EM (2012) Regulatory T-cell modulation using cyclophosphamide in vaccine approaches: a current perspective. Cancer Res 72(14):3439–3444

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  11. Lutsiak MEC, Semnani RT, De Pascalis R, Kashmiri SVS, Schlom J, Sabzevari H (2005) Inhibition of CD4(+)25+ T regulatory cell function implicated in enhanced immune response by low-dose cyclophosphamide. Blood 105(7):2862–2868

    Article  CAS  PubMed  Google Scholar 

  12. Ghiringhelli F, Menard C, Puig PE, Ladoire S, Roux S, Martin F, Solary E, Le Cesne A, Zitvogel L, Chauffert B (2007) Metronomic cyclophosphamide regimen selectively depletes CD4+CD25+ regulatory T cells and restores T and NK effector functions in end stage cancer patients. Cancer Immunol Immunother 56(5):641–648

    Article  CAS  PubMed  Google Scholar 

  13. Ercolini AM, Ladle BH, Manning EA, Pfannenstiel LW, Armstrong TD, Machiels J-PH, Bieler JG, Emens LA, Reilly RT, Jaffee EM (2005) Recruitment of latent pools of high-avidity CD8(+) T cells to the antitumor immune response. J Exp Med 201(10):1591–1602

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  14. Wan S, Pestka S, Jubin RG, Lyu YL, Tsai Y-C, Liu LF (2012) Chemotherapeutics and radiation stimulate MHC class I expression through elevated interferon-beta signaling in breast cancer cells. PLoS One 7(3):e32542

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  15. Penel N, Adenis A, Bocci G (2012) Cyclophosphamide-based metronomic chemotherapy: after 10 years of experience, where do we stand and where are we going? Crit Rev Oncol Hematol 82(1):40–50

    Article  PubMed  Google Scholar 

  16. Sharabi A, Ghera NH (2010) Breaking tolerance in a mouse model of multiple myeloma by chemoimmunotherapy. Adv Cancer Res 107:1–37

    Article  CAS  PubMed  Google Scholar 

  17. Heissig B, Ohki Y, Sato Y, Rafii S, Werb Z, Hattori K (2005) A role for niches in hematopoietic cell development. Hematology 10(3):247–253

    Article  CAS  PubMed  Google Scholar 

  18. Hatfield K, Øyan AM, Ersvaer E, Kalland K-H, Lassalle P, Gjertsen BT, Bruserud Ø (2009) Primary human acute myeloid leukaemia cells increase the proliferation of microvascular endothelial cells through the release of soluble mediators. Br J Haematol 144(1):53–68

    Article  CAS  PubMed  Google Scholar 

  19. Kruizinga RC, de Jonge HJM, Kampen KR, Walenkamp AME, de Bont ESJM (2011) Vascular Endothelial Growth Factor A isoform mRNA expression in pediatric acute myeloid leukemia. Pediatr Blood Cancer 56(2):294–297

    Article  CAS  PubMed  Google Scholar 

  20. Mourah S, Porcher R, Lescaille G, Rousselot P, Podgorniak M-P, Labarchède G, Naimi B, Medioni J, Dombret H, Calvo F (2009) Quantification of VEGF isoforms and VEGFR transcripts by qRT-PCR and their significance in acute myeloid leukemia, Int J Biol Markers 24(1):22–31

    CAS  PubMed  Google Scholar 

  21. Kuzu I, Beksac M, Arat M, Celebi H, Elhan AH, Erekul S (2004) Bone marrow microvessel density (MVD) in adult acute myeloid leukemia (AML): therapy induced changes and effects on survival. Leuk Lymphoma 45(6):1185–1190

    Article  CAS  PubMed  Google Scholar 

  22. Trujillo A, McGee C, Cogle CR (2012) Angiogenesis in acute myeloid leukemia and opportunities for novel therapies. J Oncol 2012:128608

    Article  PubMed Central  PubMed  Google Scholar 

  23. Hatfield KJ, Evensen L, Reikvam H, Lorens JB, Bruserud Ø (2012) Soluble mediators released by acute myeloid leukemia cells increase capillary-like networks. Eur J Haematol 89(6):478–490

    Article  CAS  PubMed  Google Scholar 

  24. Veiga JP, Costa LF, Sallan SE, Nadler LM, Cardoso AA (2006) Leukemia-stimulated bone marrow endothelium promotes leukemia cell survival. Exp Hematol 34(5):610–621

    Article  CAS  PubMed  Google Scholar 

  25. Schaefer C, Krause M, Fuhrhop I, Schroeder M, Algenstaedt P, Fiedler W, Rüther W, Hansen-Algenstaedt N (2008) Time-course-dependent microvascular alterations in a model of myeloid leukemia in vivo. Leukemia 22(1):59–65

    Article  CAS  PubMed  Google Scholar 

  26. Wang L, Shi W-Y, Yang F, Tang W, Gapihan G, Varna M, Shen Z-X, Chen S-J, Leboeuf C, Janin A, Zhao W-L (2011) Bevacizumab potentiates chemotherapeutic effect on T-leukemia/lymphoma cells by direct action on tumor endothelial cells. Haematologica 96(6):927–931

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  27. Zhu Z, Hattori K, Zhang H, Jimenez X, Ludwig DL, Dias S, Kussie P, Koo H, Kim HJ, Lu D, Liu M, Tejada R, Friedrich M, Bohlen P, Witte L, Rafii S (2003) Inhibition of human leukemia in an animal model with human antibodies directed against vascular endothelial growth factor receptor 2. Correlation between antibody affinity and biological activity. Leukemia 17(3):604–611

    Article  CAS  PubMed  Google Scholar 

  28. Dias S, Hattori K, Heissig B, Zhu Z, Wu Y, Witte L, Hicklin DJ, Tateno M, Bohlen P, Moore MA, Rafii S (2001) Inhibition of both paracrine and autocrine VEGF/ VEGFR-2 signaling pathways is essential to induce long-term remission of xenotransplanted human leukemias. Proc Natl Acad Sci U S A 98(19):10857–10862

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  29. He R, Liu B, Yang C, Yang RC, Tobelem G, Han ZC (2003) Inhibition of K562 leukemia angiogenesis and growth by expression of antisense vascular endothelial growth factor (VEGF) sequence. Cancer Gene Ther 10(12):879–886

    Article  CAS  PubMed  Google Scholar 

  30. Madlambayan GJ, Meacham AM, Hosaka K, Mir S, Jorgensen M, Scott EW, Siemann DW, Cogle CR (2010) Leukemia regression by vascular disruption and antiangiogenic therapy. Blood 116(9):1539–1547

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  31. Perez-Atayde AR, Sallan SE, Tedrow U, Connors S, Allred E, Folkman J (1997) Spectrum of tumor angiogenesis in the bone marrow of children with acute lymphoblastic leukemia. Am J Pathol 150(3):815–821

    CAS  PubMed Central  PubMed  Google Scholar 

  32. Wierzbowska A, Robak T, Krawczyńska A, Pluta A, Wrzesień-Kuś A, Cebula B, Robak E, Smolewski P (2008) Kinetics and apoptotic profile of circulating endothelial cells as prognostic factors for induction treatment failure in newly diagnosed acute myeloid leukemia patients. Ann Hematol 87(2):97–106

    Article  CAS  PubMed  Google Scholar 

  33. Harris NL, Jaffe ES, Diebold J, Flandrin G, Muller-Hermelink HK, Vardiman J, Lister TA, Bloomfield CD (1999) World Health Organization classification of neoplastic diseases of the hematopoietic and lymphoid tissues: report of the Clinical Advisory Committee meeting-Airlie House, Virginia, November 1997. J Clin Oncol 17(12):3835–3849

    CAS  PubMed  Google Scholar 

  34. Vacca A, Ribatti D, Ruco L, Giacchetta F, Nico B, Quondamatteo F, Ria R, Iurlaro M, Dammacco F (1999) Angiogenesis extent and macrophage density increase simultaneously with pathological progression in B-cell non-Hodgkin’s lymphomas. Br J Cancer 79(5–6):965–970

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  35. Arias V, Soares FA (2000) Vascular density (tumor angiogenesis) in non-Hodgkin’s lymphomas and florid follicular hyperplasia: a morphometric study. Leuk Lymphoma 40(1–2):157–166

    CAS  PubMed  Google Scholar 

  36. Ribatti D, Vacca A, Nico B, Fanelli M, Roncali L, Dammacco F (1996) Angiogenesis spectrum in the stroma of B-cell non-Hodgkin’s lymphomas. An immunohistochemical and ultrastructural study. Eur J Haematol 56(1–2):45–53

    CAS  PubMed  Google Scholar 

  37. Dave SS, Wright G, Tan B, Rosenwald A, Gascoyne RD, Chan WC, Fisher RI, Braziel RM, Rimsza LM, Grogan TM, Miller TP, LeBlanc M, Greiner TC, Weisenburger DD, Lynch JC, Vose J, Armitage JO, Smeland EB, Kvaloy S, Holte H, Delabie J, Connors JM, Lansdorp PM, Ouyang Q, Lister TA, Davies AJ, Norton AJ, Muller-Hermelink HK, Ott G, Campo E, Montserrat E, Wilson WH, Jaffe ES, Simon R, Yang L, Powell J, Zhao H, Goldschmidt N, Chiorazzi M, Staudt LM (2004) Prediction of survival in follicular lymphoma based on molecular features of tumor-infiltrating immune cells. N Engl J Med 351(21):2159–2169

    Article  CAS  PubMed  Google Scholar 

  38. Lenz G, Wright G, Dave SS, Xiao W, Powell J, Zhao H, Xu W, Tan B, Goldschmidt N, Iqbal J, Vose J, Bast M, Fu K, Weisenburger DD, Greiner TC, Armitage JO, Kyle A, May L, Gascoyne RD, Connors JM, Troen G, Holte H, Kvaloy S, Dierickx D, Verhoef G, Delabie J, Smeland EB, Jares P, Martinez A, Lopez-Guillermo A, Montserrat E, Campo E, Braziel RM, Miller TP, Rimsza LM, Cook JR, Pohlman B, Sweetenham J, Tubbs RR, Fisher RI, Hartmann E, Rosenwald A, Ott G, Muller-Hermelink H-K, Wrench D, Lister TA, Jaffe ES, Wilson WH, Chan WC, Staudt LM (2008) Stromal gene signatures in large-B-cell lymphomas. N Engl J Med 359(22):2313–2323

    Article  CAS  PubMed  Google Scholar 

  39. Taskinen M, Karjalainen-Lindsberg M-L, Nyman H, Eerola L-M, Leppä S (2007) A high tumor-associated macrophage content predicts favorable outcome in follicular lymphoma patients treated with rituximab and cyclophosphamide-doxorubicin-vincristine-prednisone. Clin Cancer Res 13(19):5784–5789

    Article  CAS  PubMed  Google Scholar 

  40. Ruan J, Hyjek E, Kermani P, Christos PJ, Hooper AT, Coleman M, Hempstead B, Leonard JP, Chadburn A, Rafii S (2006) Magnitude of stromal hemangiogenesis correlates with histologic subtype of non-Hodgkin’s lymphoma. Clin Cancer Res 12(19):5622–5631

    Article  CAS  PubMed  Google Scholar 

  41. Ruan J, Luo M, Wang C, Fan L, Yang SN, Cardenas M, Geng H, Leonard JP, Melnick A, Cerchietti L, Hajjar KA (2013) Imatinib disrupts lymphoma angiogenesis by targeting vascular pericytes. Blood 121(26):5192–5202

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  42. Ribatti D, Vacca A (2008) The role of microenvironment in tumor angiogenesis. Genes Nutr 3(1):29–34

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  43. Podar K, Chauhan D, Anderson KC (2009) Bone marrow microenvironment and the identification of new targets for myeloma therapy. Leukemia 23(1):10–24

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  44. Vacca A, Ria R, Semeraro F, Merchionne F, Coluccia M, Boccarelli A, Scavelli C, Nico B, Gernone A, Battelli F, Tabilio A, Guidolin D, Petrucci MT, Ribatti D, Dammacco F (2003) Endothelial cells in the bone marrow of patients with multiple myeloma. Blood 102(9):3340–3348

    Article  CAS  PubMed  Google Scholar 

  45. Vacca A, Ribatti D, Presta M, Minischetti M, Iurlaro M, Ria R, Albini A, Bussolino F, Dammacco F (1999) Bone marrow neovascularization, plasma cell angiogenic potential, and matrix metalloproteinase-2 secretion parallel progression of human multiple myeloma. Blood 93(9):3064–3073

    CAS  PubMed  Google Scholar 

  46. Giuliani N, Storti P, Bolzoni M, Palma BD, Bonomini S (2011) Angiogenesis and multiple myeloma. Cancer Microenviron 4(3):325–337

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  47. Bhutani M, Turkbey B, Tan E, Kemp TJ, Pinto LA, Berg AR, Korde N, Minter AR, Weiss BM, Mena E, Lindenberg L, Aras O, Purdue MP, Hofmann JN, Steinberg SM, Calvo KR, Choyke PL, Maric I, Kurdziel K, Landgren O (2014) Bone marrow angiogenesis in myeloma and its precursor disease: a prospective clinical trial. Leukemia 28(2):413–416

    Article  CAS  PubMed  Google Scholar 

  48. Medinger M, Fischer N, Tzankov A (2010) Vascular endothelial growth factor-related pathways in hemato-lymphoid malignancies. J Oncol 2010:729725

    Article  PubMed Central  PubMed  Google Scholar 

  49. Bolkun L, Lemancewicz D, Sobolewski K, Mantur M, Semeniuk J, Kulczynska A, Kloczko J, Dzieciol J (2013) The evaluation of angiogenesis and matrix metalloproteinase-2 secretion in bone marrow of multiple myeloma patients before and after the treatment. Adv Med Sci 58(1):118–125

    Article  CAS  PubMed  Google Scholar 

  50. Kopp H-G, Avecilla ST, Hooper AT, Rafii S (2005) The bone marrow vascular niche: home of HSC differentiation and mobilization. Physiology (Bethesda) 20:349–356

    Article  CAS  Google Scholar 

  51. Pellegrino A, Antonaci F, Russo F, Merchionne F, Ribatti D, Vacca A, Dammacco F (2004) CXCR3-binding chemokines in multiple myeloma. Cancer Lett 207(2):221–227

    Article  CAS  PubMed  Google Scholar 

  52. Otjacques E, Binsfeld M, Noel A, Beguin Y, Cataldo D, Caers J (2011) Biological aspects of angiogenesis in multiple myeloma. Int J Hematol 94(6):505–518

    Article  CAS  PubMed  Google Scholar 

  53. Pui C-H, Evans WE (2006) Treatment of acute lymphoblastic leukemia. N Engl J Med 354(2):166–178

    Article  CAS  PubMed  Google Scholar 

  54. Aricó M, Baruchel A, Bertrand Y, Biondi A, Conter V, Eden T, Gadner H, Gaynon P, Horibe K, Hunger SP, Janka-Schaub G, Masera G, Nachman J, Pieters R, Schrappe M, Schmiegelow K, Valsecchi MG, Pui C-H (2005) The seventh international childhood acute lymphoblastic leukemia workshop report: Palermo, Italy, January 29–30, 2005. Leukemia 19(7):1145–1152

    Article  PubMed  Google Scholar 

  55. Banavali SD, Goyal L, Nair R, Biswas G, Amare-Kadam P, Baisane C, Mahadik S, Gujral S, Karanth N, Arora B, Bhagwat R, Kurkure P, Parikh P (2005) A novel, efficacious therapeutic approach to patients with acute promyelocytic leukemia (APL) using differentiating agent and metronomic chemotherapy (CT). ASH Annu Meet Abstr 106(11):900

    Google Scholar 

  56. Roboz GJ, Ritchie EK, Curcio T, Provenzano J, Carlin R, Samuel M, Wittenberg B, Mazumdar M, Christos PJ, Mathew S, Allen-Bard S, Feldman EJ (2008) Arsenic trioxide and low-dose cytarabine in older patients with untreated acute myeloid leukemia, excluding acute promyelocytic leukemia. Cancer 113(9):2504–2511

    Article  CAS  PubMed  Google Scholar 

  57. Roboz GJ, Ritchie EK, Curcio T, Samuel M, Provenzano J, Segovia J, Christos PJ, Mathew S, Allen-Bard S, Feldman EJ (2011) Arsenic trioxide and low-dose cytarabine for patients with intermediate-2 and high-risk myelodysplastic syndrome. Leuk Res 35(4):522–525

    Article  CAS  PubMed  Google Scholar 

  58. Boyd D, Coleman M, Papish S, Topilow A, Kopel S, Bernhardt B, Files J, Schwartz S, Gaynor M, McDermott D (1988) COPBLAM III: infusional combination chemotherapy for diffuse large-cell lymphoma. J Clin Oncol 6(3):425–433

    CAS  PubMed  Google Scholar 

  59. Hainsworth JD, Johnson DH, Frazier SR, Greco FA (1990) Chronic daily administration of oral etoposide in refractory lymphoma. Eur J Cancer 26(7):818–821

    Article  CAS  PubMed  Google Scholar 

  60. Brugières L, Pacquement H, Le Deley M-C, Leverger G, Lutz P, Paillard C, Baruchel A, Frappaz D, Nelken B, Lamant L, Patte C (2009) Single-drug vinblastine as salvage treatment for refractory or relapsed anaplastic large-cell lymphoma: a report from the French Society of Pediatric Oncology. J Clin Oncol 27(30):5056–5061

    Article  PubMed  Google Scholar 

  61. Buckstein R, Kerbel RS, Shaked Y, Nayar R, Foden C, Turner R, Lee CR, Taylor D, Zhang L, Man S, Baruchel S, Stempak D, Bertolini F, Crump M (2006) High-Dose celecoxib and metronomic ‘low-dose’ cyclophosphamide is an effective and safe therapy in patients with relapsed and refractory aggressive histology non-Hodgkin’s lymphoma. Clin Cancer Res 12(17):5190–5198

    Article  CAS  PubMed  Google Scholar 

  62. Coleman M, Martin P, Ruan J, Furman R, Niesvizky R, Elstrom R, George P, Leonard J, Kaufmann T (2008) Low-dose metronomic, multidrug therapy with the PEP-C oral combination chemotherapy regimen for mantle cell lymphoma. Leuk Lymphoma 49(3):447–450

    Article  CAS  PubMed  Google Scholar 

  63. Coleman M, Martin P, Ruan J, Furman R, Niesvizky R, Elstrom R, George P, Kaufman TP, Leonard JP (2008) Prednisone, etoposide, procarbazine, and cyclophosphamide (PEP-C) oral combination chemotherapy regimen for recurring/refractory lymphoma: low-dose metronomic, multidrug therapy. Cancer 112(10):2228–2232

    Article  CAS  PubMed  Google Scholar 

  64. Ruan J, Martin P, Coleman M, Furman RR, Cheung K, Faye A, Elstrom R, Lachs M, Hajjar KA, Leonard JP (2010) Durable responses with the metronomic rituximab and thalidomide plus prednisone, etoposide, procarbazine, and cyclophosphamide regimen in elderly patients with recurrent mantle cell lymphoma. Cancer 116(11):2655–2664

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  65. Mwanda WO, Orem J, Fu P, Banura C, Kakembo J, Onyango CA, Ness A, Reynolds S, Johnson JL, Subbiah V, Bako J, Wabinga H, Abdallah FK, Meyerson HJ, Whalen CC, Lederman MM, Black J, Ayers LW, Katongole-Mbidde E, Remick SC (2009) Dose-modified oral chemotherapy in the treatment of AIDS-related non-Hodgkin’s lymphoma in East Africa. J Clin Oncol 27(21):3480–3488

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  66. Zhou F, Guo L, Shi H, Lin C, Hou J (2010) Continuous administration of low-dose cyclophosphamide and prednisone as a salvage treatment for multiple myeloma. Clin Lymphoma Myeloma Leuk 10(1):51–55

    Article  PubMed  Google Scholar 

  67. Suvannasankha A, Fausel C, Juliar BE, Yiannoutsos CT, Fisher WB, Ansari RH, Wood LL, Smith GG, Cripe LD, Abonour R (2007) Final report of toxicity and efficacy of a phase II study of oral cyclophosphamide, thalidomide, and prednisone for patients with relapsed or refractory multiple myeloma: a Hoosier Oncology Group Trial, HEM01-21. Oncologist 12(1):99–106

    Article  CAS  PubMed  Google Scholar 

  68. Kropff M, Bisping G, Schuck E, Liebisch P, Lang N, Hentrich M, Dechow T, Kröger N, Salwender H, Metzner B, Sezer O, Engelhardt M, Wolf H-H, Einsele H, Volpert S, Heinecke A, Berdel WE, Kienast J (2007) Bortezomib in combination with intermediate-dose dexamethasone and continuous low-dose oral cyclophosphamide for relapsed multiple myeloma. Br J Haematol 138(3):330–337

    Article  CAS  PubMed  Google Scholar 

  69. Kyriakou C, Thomson K, D’Sa S, Flory A, Hanslip J, Goldstone AH, Yong KL (2005) Low-dose thalidomide in combination with oral weekly cyclophosphamide and pulsed dexamethasone is a well tolerated and effective regimen in patients with relapsed and refractory multiple myeloma. Br J Haematol 129(6):763–770

    Article  CAS  PubMed  Google Scholar 

  70. Reece DE, Rodriguez GP, Chen C, Trudel S, Kukreti V, Mikhael J, Pantoja M, Xu W, Stewart AK (2008) Phase I-II trial of bortezomib plus oral cyclophosphamide and prednisone in relapsed and refractory multiple myeloma. J Clin Oncol 26(29):4777–4783

    Article  CAS  PubMed  Google Scholar 

  71. Reeder CB, Reece DE, Kukreti V, Chen C, Trudel S, Hentz J, Noble B, Pirooz NA, Spong JE, Piza JG, Zepeda VHJ, Mikhael JR, Leis JF, Bergsagel PL, Fonseca R, Stewart AK (2009) Cyclophosphamide, bortezomib and dexamethasone induction for newly diagnosed multiple myeloma: high response rates in a phase II clinical trial. Leukemia 23(7):1337–1341

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  72. Coleman M, Gerstein G, Topilow A, Lebowicz J, Berhardt B, Chiarieri D, Silver RT, Pasmantier MW (1987) Advances in chemotherapy for large cell lymphoma. Semin Hematol 24(2 Suppl 1):8–20

    CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Division of Hematology and Medical Oncology, Weill Cornell Medical College, New York-Presbyterian Hospital, New York, NY, USA

    Pannee Praditsuktavorn MD

  2. Division of Hematology and Medical Oncology, Department of Medicine, Center for Lymphoma and Myeloma, Weill Cornell Medical College, New York-Presbyterian Hospital, 1305 York Avenue, Room Y-766, New York, NY, 10065, USA

    Jia Ruan MD, PhD

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  1. Division of Pharmacology, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy

    Guido Bocci

  2. Department of Biological Sciences, University of Texas at El Paso, El Paso, Texas, USA

    Giulio Francia

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Praditsuktavorn, P., Ruan, J. (2014). Metronomic Chemotherapy in Hematological Malignancies. In: Bocci, G., Francia, G. (eds) Metronomic Chemotherapy. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-662-43604-2_12

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