Metronomic chemotherapy: Back to the future!

Drug News and Perspectives

Volumn 23, Issue 2, 2010, Pages 143-151

  André, Nicolas ^a,b   Padovani, Laetitia ^a   Verschuur, Arnauld ^a  

^a TIMONE HOSPITAL   (France)

^b AIX MARSEILLE UNIVERSITY   (France)

Author keywords

[No Author keywords available]

Indexed keywords

ANTIESTROGEN; BEVACIZUMAB; CAPECITABINE; CELECOXIB; CYCLOPHOSPHAMIDE; DEXAMETHASONE; ETOPOSIDE; FUMAGILLOL CHLOROACETYLCARBAMATE; GEMCITABINE; IDARUBICIN; LENALIDOMIDE; MERCAPTOPURINE; METHOTREXATE; MONOCLONAL ANTIBODY DC101; NAVELBINE; PEMETREXED; RETINOIC ACID; SUNITINIB; TAXANE DERIVATIVE; TEMOZOLOMIDE; TRASTUZUMAB; TROFOSFAMIDE; VINBLASTINE; VINCA ALKALOID; VINCRISTINE;

ACUTE LYMPHOCYTIC LEUKEMIA; ADVANCED CANCER; ANTIANGIOGENIC ACTIVITY; BREAST CANCER; CANCER CHEMOTHERAPY; CANCER COMBINATION CHEMOTHERAPY; CANCER RESISTANCE; CELL CYCLE ARREST; CLINICAL TRIAL; COLON CANCER; DRUG EFFICACY; DRUG INTERMITTENT THERAPY; DRUG RESPONSE; DRUG SENSITIVITY; EYE CANCER; GLIOBLASTOMA; GLIOMA; HUMAN; LONG TERM CARE; LOW DRUG DOSE; LUNG CANCER; MAINTENANCE THERAPY; MELANOMA; MESOTHELIOMA; METASTASIS; METRONOMIC CHEMOTHERAPY; MONOTHERAPY; NEUROBLASTOMA; NONHUMAN; OVARY CANCER; PANCREAS CANCER; PROSTATE CANCER; REGULATORY T LYMPHOCYTE; REVIEW; SKIN CANCER; SOFT TISSUE SARCOMA; TUMOR IMMUNITY;

ANGIOGENESIS INHIBITORS; ANIMALS; ANTINEOPLASTIC AGENTS; DRUG ADMINISTRATION SCHEDULE; DRUG DELIVERY SYSTEMS; DRUG RESISTANCE, NEOPLASM; HUMANS; NEOPLASMS; NEOVASCULARIZATION, PATHOLOGIC;

EID: 77952343265     PISSN: 02140934     EISSN: None     Source Type: Journal    
DOI: 10.1358/dnp.2010.23.2.1475913     Document Type: Review

References (93)

1. Longley, D.B., Johnston, P.G. Molecular mechanisms of drug resistance. J Pathol 2005, 205(2): 275-292 (Pubitemid 40227997)
2. Frei, E., 3rd, Canellos, G.P. Dose: a critical factor in cancer chemotherapy. Am J Med 1980, 69(4): 585-594
3. Ferrara, N., Kerbel, R.S. Angiogenesis as a therapeutic target. Nature 2005, 438(7070): 967-974
4. Kerbel, R.S. Tumor angiogenesis. N Engl J Med 2008, 358(19): 2039-2049
5. Folkman, J. Tumor angiogenesis: therapeutic implications. N Engl J Med 1971, 285(21): 1182-1186
6. Kerbel, R.S. Inhibition of tumor angiogenesis as a strategy to circumvent acquired resistance to anti-cancer therapeutic agents. Bioessays 1991, 13(1): 31-36
7. Miller, K., Wang, M., Gralow, J. et al. Paclitaxel plus bevacizumab versus paclitaxel alone for metastatic breast cancer. N Engl J Med 2007, 357(26): 2666-2676
8. Hurwitz, H., Fehrenbacher, L., Novotny, W. et al. Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N Engl J Med 2004, 350(23): 2335-2342
9. Ebos, J.M., Lee, C.R., Cruz-Munoz, W., Bjarnason, G.A., Christensen, J.G., Kerbel, R.S. Accelerated metastasis after short-term treatment with a potent inhibitor of tumor angiogenesis. Cancer Cell 2009, 15(3): 232-239
10. Klement, G., Baruchel, S., Rak, J. et al. Continuous low-dose therapy with vinblastine and VEGF receptor-2 antibody induces sustained tumor regression without overt toxicity. J Clin Invest 2000, 105(8): R15-24.
11. Browder, T., Butterfield, C.E., Kraling, B.M., Shi, B., Marshall, B., O'Reilly, M.S., Folkman, J. Antiangiogenic scheduling of chemotherapy improves efficacy against experimental drug-resistant cancer. Cancer Res 2000, 60(7): 1878-1886 (Pubitemid 30207647)
12. Hanahan, D., Bergers, G., Bergsland, E. Less is more, regularly: metronomic dosing of cytotoxic drugs can target tumor angiogenesis in mice. J Clin Invest 2000, 105(8): 1045-1047 (Pubitemid 30217688)
13. Fidler, I.J., Ellis, L.M. Chemotherapeutic drugs-more really is not better. Nat Med 2000, 6(5): 500-502
14. Gasparini, G. Metronomic scheduling: the future of chemotherapy? Lancet Oncol 2001, 2(12): 733-740
15. Laquente, B., Vinals, F., Germa, J.R. Metronomic chemotherapy: an antiangiogenic scheduling. Clin Transi Oncol 2007, 9(2): 93-98
16. Scharovsky, O.G., Mainetti, L.E., Rozados, V.R. Metronomic chemotherapy: changing the paradigm that more is better. Curr Oncol 2009, 16(2): 7-15.
17. Kerbel, R.S., Kamen, B.A. The anti-angiogenic basis of metronomic chemotherapy. Nat Rev Cancer 2004, 4(6): 423-436
18. Colleoni, M., Rocca, A., Sandri, M.T. et al. Low-dose oral methotrexate and cyclophosphamide in metastatic breast cancer: antitumor activity and correlation with vascular endothelial growth factor levels. Ann Oncol 2002, 13(1): 73-80.
19. Damber, J.E., Vallbo, C., Albertsson, P., Lennernas, B., Norrby, K. The anti-tumour effect of low-dose continuous chemotherapy may partly be mediated by thrombospondin. Cancer Chemother Pharmacol 2006, 58(3): 354-360 (Pubitemid 43800739)
20. Tonini, G., Schiavon, G., Silletta, M., Vincenzi, B., Santini, D. Antiangiogenic properties of metronomic chemotherapy in breast cancer. Future Oncol 2007, 3(2): 183-190 (Pubitemid 46592726)
21. Sanchez-Munoz, A., Perez-Ruiz, E., Ribelles, N., Marquez, A., Alba, E. Maintenance treatment in metastatic breast cancer. Expert Rev Anticancer Ther 2008, 8(12): 1907-1912
22. Andre, N., Pasquier, E., Verschuur, A., Sterba, J., Gentet, J.C., Rossler, J. [Metronomic chemotherapy in pediatric oncology, hype or hope?]. Arch Pediatr 2009, 16(8): 1158-1165
23. Stempak, D., Seely, D., Baruchel, S. Metronomic dosing of chemotherapy: applications in pediatric oncology. Cancer Invest 2006, 24(4): 432-443 (Pubitemid 43932689)
24. Garcia, A.A., Hirte, H., Fleming, G. et al. Phase II clinical trial of bevacizumab and low-dose metronomic oral cyclophosphamide in recurrent ovarian cancer: a trial of the California, Chicago, and Princess Margaret Hospital phase II consortia. J Clin Oncol 2008, 26(1): 76-82.
25. Lord, R., Nair, S., Schache, A., Spicer, J., Somaihah, N., Khoo, V., Pandha, H. Low dose metronomic oral cyclophosphamide for hormone resistant prostate cancer: a phase II study. J Urol 2007, 177(6): 2136-40; discussion 40.
26. Buckstein, R., Kerbel, R.S., Shaked, Y. et al. 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 2006, 12(17): 5190-5198
27. Pasquier, E., Andre, N., Braguer, D. Targeting microtubules to inhibit angiogenesis and disrupt tumour vasculature: implications for cancer treatment. Curr Cancer Drug Targets 2007, 7(6): 566-581
28. Hainsworth, J.D. Extended-schedule oral etoposide in selected neoplasms and overview of administration and scheduling issues. Drugs 1999, 58(Suppl 3): 51-56
29. Kushner, B.H., Kramer, K., Cheung, N.K. Oral etoposide for refractory and relapsed neuroblastoma. J Clin Oncol 1999, 17(10): 3221-3225 (Pubitemid 29470655)
30. Ma, W.W., Adjei, A.A. Novel agents on the horizon for cancer therapy. CA Cancer J Clin 2009, 59(2): 111-137
31. Andre, N., Pasquier, E. For cancer, seek and destroy or live and let live? Nature 2009, 460(7253): 324.
32. Kieran, M.W., Turner, C.D., Rubin, J.B. et al. A feasibility trial of antiangiogenic (metronomic) chemotherapy in pediatric patients with recurrent or progressive cancer. J Pediatr Hematol Oncol 2005, 27(11): 573-581
33. Broxterman, H.J., Lankelma, J., Hoekman, K. Resistance to cytotoxic and anti-angiogenic anticancer agents: similarities and differences. Drug Resist Updat 2003, 6(3): 111-127 (Pubitemid 36890336)
34. Streubel, B., Chott, A., Huber, D., Exner, M., Jager, U., Wagner, O., Schwarzinger, I. Lymphoma-specific genetic aberration's in microvascular endothelial cells in B-cell lymphomas. N Engl J Med 2004, 351(3): 250-259 (Pubitemid 38916042)
35. Hida, K., Hida, Y., Amin, D.N., Flint, A.F., Panigrahy, D., Morton, C.C., Klagsbrun, M. Tumor-associated endothelial cells with cytogenetic abnormalities. Cancer Res 2004, 64(22): 8249-8255 (Pubitemid 39491762)
36. Zitvogel, L., Apetoh, L., Ghiringhelli, F., Andre, F., Tesniere, A., Kroemer, G. The anticancer immune response: indispensable for therapeutic success? J Clin Invest 2008, 118(6): 1991-2001.
37. Banissi, C., Ghiringhelli, F., Chen, L., Carpentier, A.F. Treg depletion with a low-dose metronomic temozolomide regimen in a rat glioma model. Cancer Immunol Immunother 2009, 58(10): 1627-1634
38. Ghiringhelli, F., Larmonier, N., Schmitt, E. et al. CD4+CD25+ regulatory T cells suppress tumor immunity but are sensitive to cyclophosphamide which allows immunotherapy of established tumors to be curative. Eur J Immunol 2004, 34(2): 336-344
39. Ghiringhelli, F., Menard, C., Puig, P.E. et al. Metronomic cyclophosphamide regimen selectively depletes CD4+CD25+ regulatory T cells and restores T and NK effector functions in end stage cancer patients. Cancer Immunol lmmunother 2007, 56(5): 641-648 (Pubitemid 46348738)
40. van der Most, R.G., Currie, A.J., Mahendran, S. et al. Tumor eradication after cyclophosphamide depends on concurrent depletion of regulatory T cells: a role for cycling TNFR2-expressing effector-suppressor T cells in limiting effective chemotherapy. Cancer Immunol lmmunother 2009, 58(8): 1219-1228
41. Bergers, G., Benjamin, L.E. Tumorigenesis and the angiogenic switch. Nat Rev Cancer 2003, 3(6): 401-410
42. Indraccolo, S., Favaro, E., Amadori, A. Dormant tumors awaken by a short-term angiogenic burst: the spike hypothesis. Cell Cycle 2006, 5(16): 1751-1755 (Pubitemid 44435317)
43. Aguirre-Ghiso, J.A. Models, mechanisms and clinical evidence for cancer dormancy. Nat Rev Cancer 2007, 7(11): 834-846
44. Ohtani, N., Mann, D.J., Hara, E. Cellular senescence: its role in tumor suppression and aging. Cancer Sci 2009, 100(5): 792-797
45. Weinhold, K.J., Miller, D.A., Wheelock, E.F. The tumor dormant state. Comparison of L5178Y cells used to establish dormancy with those that emerge after its termination. J Exp Med 1979, 149(3): 745-757
46. Schirrmacher, V. T-cell immunity in the induction and maintenance of a tumour dormant state. Semin Cancer Biol 2001, 11(4): 285-295 (Pubitemid 32799906)
47. Quesnel, B. Tumor dormancy and immunoescape. APMIS 2008, 116(7-8): 685-694
48. Merlo, L.M., Pepper, J.W., Reid, B.J., Maley, C.C. Cancer as an evolutionary and ecological process. Nat Rev Cancer 2006, 6(12): 924-935
49. Andre, N., Pasquier, E. Response to 'Intermittent androgen blockade should be regarded as standard therapy in prostate cancer'. Nat Clin Pract Oncol 2009, 6(2): E1.
50. Kavallaris, M., Kuo, D.Y., Burkhart, C.A., Regl, D.L., Norris, M.D., Haber, M., Horwitz, S.B. Taxol-resistant epithelial ovarian tumors are associated with altered expression of specific beta-tubulin isotypes. J Clin Invest 1997, 100(5): 1282-1293 (Pubitemid 27386315)
51. Schibler, M.J., Cabrai, F. Taxol-dependent mutants of Chinese hamster ovary cells with alterations in alpha- and beta-tubulin. J Cell Biol 1986, 102(4): 1522-1531 (Pubitemid 16038095)
52. Slater, L.M., Sweet, P., Hsu, T.C., Chan, P.K. Novel nucleolar and nuclear morphology in a vincristine-dependent human leukemia cell line (L100). Exp Cell Res 1992, 198(1): 170-174
53. Yang, C.P., Verdier-Pinard, P., Wang, F. et al. A highly epothilone B-resistant A549 cell line with mutations in tubulin that confer drug dependence. Mol Cancer Ther 2005, 4(6): 987-995
54. Cabrai, F.R. Isolation of Chinese hamster ovary cell mutants requiring the continuous presence of taxol for cell division. J Cell Biol 1983, 97(1): 22-29
55. Sabnis, G.J., Jelovac, D., Long, B., Brodie, A. The role of growth factor receptor pathways in human breast cancer cells adopted to long-term estrogen deprivation. Cancer Res 2005, 65(9): 3903-3910
56. Pietras, K., Hanahan, D. A multitargeted, metronomic, and maximum-tolerated dose "chemo-switch" regimen is antiangiogenic, producing objective responses and survival benefit in a mouse model of cancer. J Clin Oncol 2005, 23(5): 939-952
57. Blansfield, J.A., Caragacianu, D., Alexander, H.R., 3rd et al. Combining agents that target the tumor microenvironment improves the efficacy of anticancer therapy. Clin Cancer Res 2008, 14(1): 270-280
58. Dellapasqua, S., Bertolini, F., Bagnardi, V. et al. Metronomic cyclophosphamide and capecitabine combined with bevacizumab in advanced breast cancer. J Clin Oncol 2008, 26(30): 4899-4905
59. Jurado, J.M., Sanchez, A., Pajares, B., Perez, E., Alonso, L., Alba, E. Combined oral cyclophosphamide and bevacizumab in heavily pre-treated ovarian cancer. Clin Transl Oncol 2008, 10(9): 583-586
60. Jordan, V.C. The 38th David A. Karnofsky lecture: the paradoxical actions of estrogen in breast cancer-survival or death? J Clin Oncol 2008, 26(18): 3073-3082
61. Viani, G.A., Afonso, S.L., Stefano, E.J., De Fendi, L.I., Soares, F.V. Adjuvant trastuzumab in the treatment of her-2-positive early breast cancer: a meta-analysis of published randomized trials. BMC Cancer 2007, 7: 153.
62. Orlando, L., Cardillo, A., Rocca, A. et al. Prolonged clinical benefit with metronomic chemotherapy in patients with metastatic breast cancer. Anticancer Drugs 2006, 17(8): 961-967 (Pubitemid 44350615)
63. Seruga, B., Tannock, I.F. Intermittent androgen blockade should be regarded as standard therapy in prostate cancer. Nat Clin Pract Oncol 2008, 5(10): 574-576
64. Nelius, T., Klatte, T., de Riese, W., Haynes, A., Filleur, S. Clinical outcome of patients with docetaxel-resistant hormone-refractory prostate cancer treated with second-line cyclophosphamide-based metronomic chemotherapy. Med Oncol 2009.
65. Fontana, A., Galli, L., Fioravanti, A. et al. Clinical and pharmacodynamic evaluation of metronomic cyclophosphamide, celecoxib, and dexamethasone in advanced hormone-refractory prostate cancer. Clin Cancer Res 2009, 15(15): 4954-4962
66. Matthay, K.K., Reynolds, C.P., Seeger, R.C. et al. Long-term results for children with high-risk neuroblastoma treated on a randomized trial of myeloablative therapy followed by 13-cis-retinoic acid: a children's oncology group study. J Clin Oncol 2009, 27(7): 1007-1013
67. Matthay, K.K., Villablanca, J.G., Seeger, R.C. et al. Treatment of high-risk neuroblastoma with intensive chemotherapy, radiotherapy, autologous bone marrow transplantation, and 13-cis-retinoic acid. Children's Cancer Group. N Engl J Med 1999, 341(16): 1165-1173
68. Sterba, J., Valik, D., Mudry, P. et al. Combined biodifferentiating and antiangiogenic oral metronomic therapy is feasible and effective in relapsed solid tumors in children: single-center pilot study. Ontologie 2006, 29(7): 308-313 (Pubitemid 44022404)
69. Aguilera, D., Hayes-Jordan, A., Anderson, P., Woo, S., Pearson, M., Green, H. Outpatient and home chemotherapy with novel local control strategies in desmoplastic small round cell tumor. Sarcoma 2008, 2008: 261589.
70. Linden, O., Greift, L., Wahlberg, P., Vinge, E., Kjellen, E. Chemorefractory rhabdomyosarcoma treated with radiotherapy, bevacizumab, statins and surgery and maintenance with bevacizumab and chemotherapy. Onkologie 2008, 31(7): 391-393
71. Klingebiel, T., Boos, J., Beske, F. et al. Treatment of children with metastatic soft tissue sarcoma with oral maintenance compared to high dose chemotherapy: report of the HD CWS-96 trial. Pediatr Blood Cancer 2008, 50(4): 739-745 (Pubitemid 351354776)
72. Mok, T.S., Ramalingam, S.S. Maintenance therapy in nonsmall-cell lung cancer: a new treatment paradigm. Cancer 2009, 115(22): 5143-5154
73. Clarke, J.L., Iwamoto, F.M., Sul, J. et al. Randomized phase II trial of chemoradiotherapy followed by either dose-dense or metronomic temozolomide for newly diagnosed glioblastoma. J Clin Oncol 2009, 27(23): 3861-3867
74. Grodman, H., Wolfe, L., Kretschmar, C. Outcome of patients with recurrent medulloblastoma or central nervous system germinoma treated with low dose continuous intravenous etoposide along with dose-intensive chemotherapy followed by autologous hematopoietic stem cell rescue. Pediatr Blood Cancer 2009, 53(1): 33-36
75. Woywodt, A., Haubitz, M., Buchholz, S., Hertenstein, B. Counting the cost: markers of endothelial damage in hematopoietic stem cell transplantation. Bone Marrow Transplant 2004, 34(12): 1015-1023 (Pubitemid 40028832)
76. Grosch, S., Maier, T.J., Schiffmann, S., Geisslinger, G. Cyclooxygenase-2 (COX-2)-independent anticarcinogenic effects of selective COX-2 inhibitors. J Natl Cancer Inst 2006, 98(11): 736-747 (Pubitemid 43983297)
77. Schonthal, A.H. Direct non-cyclooxygenase-2 targets of celecoxib and their potential relevance for cancer therapy. Br J Cancer 2007, 97(11): 1465-1468
78. Altorki, N.K., Keresztes, R.S., Port, J.L. et al. Celecoxib, a selective cyclo-oxygenase-2 inhibitor, enhances the response to preoperative paclitaxel and carboplatin in early-stage non-small-cell lung cancer. J Clin Oncol 2003, 21(14): 2645-2650
79. Pruthi, R.S., Derksen, J.E., Moore, D. A pilot study of use of the cyclooxygenase-2 inhibitor celecoxib in recurrent prostate cancer after definitive radiation therapy or radical prostatectomy. BJU Int 2004, 93(3): 275-278
80. Natale, R.B. Irinotecan, cisplatin/carboplatin, and COX-2 inhibition in small-cell lung cancer. Oncology (Williston Park) 2003, 17(7 Suppl 7): 22-26
81. Gasparini, G., Meo, S., Cornelia, G. et al. The combination of the selective cyclooxygenase-2 inhibitor celecoxib with weekly paclitaxel is a safe and active second-line therapy for nonsmall cell lung cancer: a phase II study with biological correlates. Cancer J 2005, 11(3): 209-216
82. Crane, C.H., Mason, K., Janjan, N.A., Milas, L. Initial experience combining cyclooxygenase-2 inhibition with chemoradiation for locally advanced pancreatic cancer. Am J Clin Oncol 2003, 26(4): S81-4.
83. Bernard, M.P., Bancos, S., Sime, P.J., Phipps, R.P. Targeting cyclooxygenase-2 in hematological malignancies: rationale and promise. Curr Pharm Des 2008, 14(21): 2051-2060
84. Pozzi, A., Capdevila, J.H. PPARalpha ligands as antitumorigenic and antiangiogenic agents. PPAR Res 2008, 2008: 906542.
85. Panigrahy, D., Kaipainen, A., Huang, S. et al. PPARalpha agonist fenofibrate suppresses tumor growth through direct and indirect angiogenesis inhibition. Proc Natl Acad Sci U S A 2008, 105(3): 985-990 (Pubitemid 351282068)
86. Pozzi, A., Ibanez, M.R., Gatica, A.E. et al. Peroxisomal proliferator-activated receptor-alpha-dependent inhibition of endothelial cell proliferation and tumorigenesis. J Biol Chem 2007, 282(24): 17685-17695
87. Araki, H., Tamada, Y., Imoto, S. et al. Analysis of PPARalpha-dependent and PPARalpha-independent transcript regulation following fenofibrate treatment of human endothelial cells. Angiogenesis 2009, 12(3): 221-229
88. Leaute-Labreze, C., Dumas de la Roque, E., Hubiche, T., Boralevi, F., Thambo, J.B., Taieb, A. Propranolol for severe hemangiomas of infancy. N Engl J Med 2008, 358(24): 2649-51.
89. Siegfried, E.C., Keenan, W.J., Al-Jureidini, S. More on propranolol for hemangiomas of infancy. N Engl J Med 2008, 359(26): 2846.
90. Sommers Smith, S.K., Smith, D.M. Beta blockade induces apoptosis in cultured capillary endothelial cells. In Vitro Cell Dev Biol Anim 2002, 38(5): 298-304.
91. Shaked, Y., Emmenegger, U., Man, S., Cervi, D., Bertolini, F., Ben-David, Y., Kerbel, R.S. Optimal biologic dose of metronomic chemotherapy regimens is associated with maximum antiangiogenic activity. Blood 2005, 106(9): 3058-3061
92. Jain, R.K., Duda, D.G., Willett, C.G. et al. Biomarkers of response and resistance to antiangiogenic therapy. Nat Rev Clin Oncol 2009, 6(6): 327-338
93. Stempak, D., Gammon, J., Halton, J., Moghrabi, A., Koren, G., Baruchel, S. A pilot pharmacokinetic and antiangiogenic biomarker study of celecoxib and low-dose metronomic vinblastine or cyclophosphamide in pediatric recurrent solid tumors. J Pediatr Hematol Oncol 2006, 28(11): 720-728