Cancer Treatment Reviews
Volume 30, Issue 6 , Pages 495-513 , October 2004

Endothelial cell effects of cytotoxics: balance between desired and unwanted effects

References 

  1. Carmeliet P, Jain RK. Angiogenesis in cancer and other diseases. Nature. 2000;407:249–527
  2. Folkman J. Tumor angiogenesis: therapeutic implications. N. Engl. J. Med. 1971;285:1182–1186
  3. Dvorak HF, Nagy JA, Feng D, Brown LF, Dvorak AM. Vascular permeability factor/vascular endothelial growth factor and the significance of microvascular hyperpermeability in angiogenesis. Curr. Top. Microbiol. Immunol. 1999;237:97–132
  4. Folkman J. What is the evidence that tumors are angiogenesis dependent?. J. Natl. Cancer Inst. 1990;82:4–6
  5. Boehm T, Folkman J, Browder T, O'Reilly MS. Antiangiogenic therapy of experimental cancer does not induce acquired drug resistance. Nature. 1997;390:404–407
  6. Kerbel RS, Viloria-Petit A, Klement G, Rak J. `Accidental' anti-angiogenic drugs: anti-oncogene directed signal transduction inhibitors and conventional chemotherapeutic agents as examples. Eur. J. Cancer. 2000;36:1248–1257
  7. Adamson IY. Pulmonary toxicity of bleomycin. Environ. Health Perspect. 1976;16:119–125
  8. Doll DC, Yarbro JW. Vascular toxicity associated with antineoplastic agents. Semin. Oncol. 1992;19:580–596
  9. Hansen SW, Olsen N, Rossing N, Rorth M. Vascular toxicity and the mechanism underlying Raynaud's phenomenon in patients treated with cisplatin, vinblastine and bleomycin. Ann. Oncol. 1990;1:289–292
  10. Harrell RM, Sibley R, Vogelzang NJ. Renal vascular lesions after chemotherapy with vinblastine, bleomycin, and cisplatin. Am. J. Med. 1982;73:429–433
  11. St Croix B, Rago C, Velculescu V, et al.  Genes expressed in human tumor endothelium. Science. 2000;289:1197–1202
  12. Carmeliet P, Jain RK. Angiogenesis in cancer and other diseases. Nature. 2000;407:249–257
  13. Hobson B, Denekamp J. Endothelial proliferation in tumours and normal tissues: continuous labelling studies. Br. J. Cancer. 1984;49:405–413
  14. Hanahan D, Folkman J. Patterns and emerging mechanisms of the angiogenic switch during tumorigenesis. Cell. 1996;86:353–364
  15. Holash J, Maisonpierre PC, Compton D, et al.  Vessel cooption, regression, and growth in tumors mediated by angiopoietins and VEGF. Science. 1999;284:1994–1998
  16. Folberg R, Hendrix MJ, Maniotis AJ. Vasculogenic mimicry and tumor angiogenesis. Am. J. Pathol. 2000;156:361–381
  17. Patan S, Alvarez MJ, Schittny JC, Burri PH. Intussusceptive microvascular growth: a common alternative to capillary sprouting. Arch. Histol. Cytol. 1992;55(Suppl):65–75
  18. Rehman J, Li J, Orschell CM, March KL. Peripheral blood “endothelial progenitor cells” are derived from monocyte/macrophages and secrete angiogenic growth factors. Circulation. 2003;107:1164–1169
  19. Bergers G, Song S, Meyer-Morse N, Bergsland E, Hanahan D. Benefits of targeting both pericytes and endothelial cells in the tumor vasculature with kinase inhibitors. J. Clin. Invest. 2003;111:1287–1295
  20. Fajardo LF. The complexity of endothelial cells. A review. Am. J. Clin. Pathol. 1989;92:241–250
  21. Pasqualini R, Koivunen E, Kain R, et al.  Aminopeptidase N is a receptor for tumor-homing peptides and a target for inhibiting angiogenesis. Cancer Res. 2000;60:722–727
  22. Carmeliet P. Angiogenesis in health and disease. Nat. Med. 2003;9:653–660
  23. Eriksson U, Alitalo K. VEGF receptor 1 stimulates stem-cell recruitment and new hope for angiogenesis therapies. Nat. Med. 2002;8:775–777
  24. Heissig B, Hattori K, Dias S, et al.  Recruitment of stem and progenitor cells from the bone marrow niche requires MMP-9 mediated release of kit-ligand. Cell. 2002;109:625–637
  25. Rafii S, Lyden D. Therapeutic stem and progenitor cell transplantation for organ vascularization and regeneration. Nat. Med. 2003;9:702–712
  26. Mancuso P, Burlini A, Pruneri G, Goldhirsch M, Bertolini F. Resting and activated endothelial cells are increased in the peripheral blood of cancer patients. Blood. 2003;97:3658–3661
  27. Ezaki T, Baluk P, Thurston G, La Barbara A, Woo C, McDonald DM. Time course of endothelial cell proliferation and microvascular remodeling in chronic inflammation. Am. J. Pathol. 2001;158:2043–2055
  28. Abramsson A, Berlin O, Papayan H, Paulin D, Shani M, Betsholtz C. Analysis of mural cell recruitment to tumor vessels. Circulation. 2002;105:112–117
  29. Nehls V, Drenckhahn D. Heterogeneity of microvascular pericytes for smooth muscle type alpha- actin. J. Cell Biol. 1991;113:147–154
  30. Benjamin LE, Hemo I, Keshet E. A plasticity window for blood vessel remodelling is defined by pericyte coverage of the preformed endothelial network and is regulated by PDGF-B and VEGF. Development. 1998;25:1591–1598
  31. Maxwell PH, Pugh CW, Ratcliffe PJ. Activation of the HIF pathway in cancer. Curr. Opin. Genet. Dev. 2001;11:293–299
  32. Wenger RH. Cellular adaptation to hypoxia: O2-sensing protein hydroxylases, hypoxia-inducible transcription factors, and O2-regulated gene expression. FASEB J. 2002;16:1151–1162
  33. Doll JA, Reiher FK, Crawford SE, Pins MR, Campbell SC, Bouck NP. Thrombospondin-1, vascular endothelial growth factor and fibroblast growth factor-2 are key functional regulators of angiogenesis in the prostate. Prostate. 2001;49:293–305
  34. Maeshima Y, Sudhakar A, Lively JC, et al.  Tumstatin, an endothelial cell-specific inhibitor of protein synthesis. Science. 2002;295:140–143
  35. Guo YL, Wang S, Colman RW. Kininostatin, an angiogenic inhibitor, inhibits proliferation and induces apoptosis of human endothelial cells. Arterioscler. Thromb. Vasc. Biol. 2001;21:1427–1433
  36. Reinmuth N, Stoeltzing O, Liu W, et al.  Endothelial survival factors as targets for antineoplastic therapy. Cancer J. 2001;7(Suppl 3):S109–S119
  37. Lennernas B, Albertsson P, Lennernas H, Norrby K. Chemotherapy and anti-angiogenesis: drug-specific, dose-related effects. Acta Oncol. 2003;42:294–303
  38. Belotti D, Vergani V, Drudis T, et al.  The microtubule-affecting drug paclitaxel has antiangiogenic activity. Clin. Cancer Res. 1996;2:1843–1849
  39. Browder T, Butterfield CE, Kraling BM, et al.  Antiangiogenic scheduling of chemotherapy improves efficacy against experimental drug-resistant cancer. Cancer Res. 2000;60:1878–1886
  40. Clements MK, Jones CB, Cumming M, Daoud SS. Antiangiogenic potential of camptothecin and topotecan. Cancer Chemother. Pharmacol. 1999;44:411–416
  41. Hirata S, Matsubara T, Saura R, Tateishi H, Hirohata K. Inhibition of in vitro vascular endothelial cell proliferation: in vivo neovascularization by low-dose methotrexate. Arthritis Rheum. 1989;32:1065–1073
  42. Schirner M, Hoffmann J, Menrad A, Schneider MR. Anti-angiogenic chemotherapeutic agents: characterization in comparison to their tumor growth inhibition in human renal cell carcinoma models. Clin. Cancer Res. 1998;4:1331–1336
  43. Bocci G, Francia G, Man S, Lwaler J, Kerbel RS. Thrombospondin-1, a mediator of the angiogenic effects of low-dose metronomic chemotherapy. Proc. Natl. Acad. Sci. USA. 2003;100:12917–12922
  44. Miller KD, Sweeney CJ, Sledge GW. Redefining the target: chemotherapeutics as antiangiogenics. J. Clin. Oncol. 2001;19:1195–1206
  45. Vacca A, Iurlaro M, Ribatti D, et al.  Antiangiogenesis is produced by nontoxic doses of vinblastine. Blood. 1999;94:4143–4155
  46. Licciardello JT, Moake JL, Rudy CK, Karp DD, Hong WK. Elevated plasma von Willebrand factor levels and arterial occlusive complications associated with cisplatin-based chemotherapy. Oncology. 1985;42:296–300
  47. Roca E, Bruera E, Politi PM, et al.  Vinca alkaloid-induced cardiovascular autonomic neuropathy. Cancer Treat. Rep. 1985;69:149–151
  48. Moseley PL, Hemken C, Hunninghake GW. Augmentation of fibroblast proliferation by bleomycin. J. Clin. Invest. 1986;78:1150–1154
  49. Doll DC, Yarbro JW. Vascular toxicity associated with chemotherapy and hormonotherapy. Curr. Opin. Oncol. 1994;6:345–350
  50. Lorenzo E, Ruiz-Ruiz C, Quesada AJ, et al.  Doxorubicin induces apoptosis and CD95 gene expression in human primary endotheilal cells through a p53-dependent mechanism. J. Biol. Chem. 2002;277:10883–10892
  51. Meinardi MT, Gietema JA, van Veldhuisen DJ, van der Graaf WT, de Vries EG, Sleijfer DT. Long-term chemotherapy-related cardiovascular morbidity. Cancer Treat. Rev. 2000;26:429–447
  52. Zafrani ES. Drug-induced vascular lesions of the liver. Anat. Pathol. 1997;2:135–145
  53. Chabner BA. Cytotoxic agents in the era of molecular targets and genomics. Oncologist. 2002;7:34–41
  54. Kerbel RS. Tumor angiogenesis: past, present and the near future. Carcinogenesis. 2000;21:505–515
  55. Los M, Voest EE. The potential role of antivascular therapy in the adjuvant and neoadjuvant treatment of cancer. Semin. Oncol. 2001;28:93–105
  56. Olmsted JB, Borisy GG. Microtubules. Annu. Rev. Biochem. 1973;42:507–540
  57. Clarke CS, Otridge BW, Carney DN. Thromboembolism. A complication of weekly chemotherapy in the treatment of non-Hodgkin's lymphoma. Cancer. 1990;66:2027–2030
  58. Dexeus F, Logothetis CJ, Samuels ML, Hossan E, von Eschenbach AC. Continuous infusion of vinblastine for advanced hormone-refractory prostate cancer. Cancer Treat. Rep. 1985;69:885–886
  59. Doll DC, List AF, Greco FA, Hainsworth JD, Hande KR, Johnson DH. Acute vascular ischemic events after cisplatin-based combination chemotherapy for germ cell tumors of the testis. Ann. Int. Med. 1986;105:48–51
  60. Lejonc JL, Vernant JP, Macquin J, Castaigne A. Myocardial infarction following vinblastine treatment. Lancet. 1980;2:692
  61. Meinardi MT, Gietema JA, van der Graaf WT, et al.  Cardiovascular morbidity in long-term survivors of metastatic testicular cancer. J. Clin. Oncol. 2000;18:1725–1732
  62. Samuels BL, Vogelzang NJ, Kennedy BJ. Severe vascular toxicity associated with vinblastine, bleomycin and cisplatin chemotherapy. Cancer Chemother. Pharmacol. 1987;19:253–256
  63. Subar M, Muggia FM. Apparent myocardial ischemia associated with vinblastine administration. Cancer Treat. Rep. 1986;70:690–691
  64. Vogelzang NJ, Bosl GJ, Johnson K, Kennedy BJ. Raynaud's phenomenon: a common toxicity after combination chemotherapy for testicular cancer. Ann. Int. Med. 1981;95:288–292
  65. Stoter G, Koopman A, Vendrik CJP, et al.  Ten-year survival and late sequelae in testicular cancer patients treated with cisplatin, vinblastine, and bleomycin. J. Clin. Oncol. 1989;7:1099–1104
  66. Bokemeyer C, Berger CC, Kuczyk MA, Schmoll HJ. Evaluation of long-term toxicity after chemotherapy for testicular cancer. J. Clin. Oncol. 1996;14:2923–2932
  67. Williams SD, Birch R, Einhorn LH, Irwin L, Greco FA, Loehrer PJ. Treatment of dissiminated germ-cell tumors with cisplatin, bleomycine and either vinblastine or etoposide. N. Engl. J. Med. 1987;316:1435–1440
  68. Owellen RJ, Hartke CA, Hains FO. Pharmacokinetics and metabolism of vinblastine in humans. Cancer Res. 1977;37:2597–2602
  69. Inaba M, Kobayashi T, Tashiro T, et al.  Evaluation of antitumor activity in a human breast tumor/nude mouse model with a special emphasis on treatment dose. Cancer. 2003;64:1577–1582
  70. Tashiro T, Inaba M, Kobayashi T, et al.  Responsiveness of human lung cancer/nude mouse to antitumor agents in a model using clinically equivalent doses. Cancer Chemother. Pharmacol. 1989;24:187–192
  71. 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:R15–24
  72. 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;105:1045–1047
  73. Fidler IJ, Ellis LM. Chemotherapeutic drugs-more really is not better. Nat. Med. 2000;6:500–502
  74. Kerbel RS, Klement G, Pritchard KI, Kamen B. Continuous low-dose anti-angiogenic/metronomic chemotherapy: from the research laboratory into the oncology clinic. Ann. Oncol. 2002;13:12–15
  75. Ratain MJ, Vogelzang NJ. Phase I and pharmacological study of vinblastine by prolonged continuous infusion. Cancer Res. 1986;46:4827–4830
  76. Hahnfeldt P, Folkman J, Hlatky L. Minimizing long-term tumor burden: the logic for metronomic chemotherapeutic dosing and its anti-angiogenic basis. J. Theor. Biol. 2003;220:545–554
  77. Lokich JJ, Zipoli TE, Perri J, Bothe A. Protracted vinblastine infusion. Phase I–II study in malignant melanoma and other tumors. Am. J. Clin. Oncol. 1984;7:551–553
  78. Ibrahim NK, Rahman Z, Valero V, et al.  Phase II study of vinorelbine administered by 96-hour infusion in patients with advanced breast cancer carcinoma. Cancer. 1999;86:1251–1257
  79. Johnson SA, Harper P, Hortobagyi GN. Vinorelbine: an overview. Cancer Treat. Rev. 1996;22:127–142
  80. Kamen BA, Rubin E, Aisner J, Glatstein E. High-time chemotherapy or high time for low dose. J. Clin. Oncol. 2000;18:2935–2937
  81. Yu JL, Rak JW, Coomber BL, Hicklin DJ, Kerbel RS. Effect of p53 status on tumor response to antiangiogenic therapy. Science. 2002;295:1526–1528
  82. Choy H. Taxanes in combined-modality therapy for solid tumors. Oncology. 1999;13:23–28
  83. Chan S, Friedrichs K, Noel D, et al.  Prospective randomized trial of docetaxel versus doxorubicin in patients with metastatic breast cancer. The 303 Study Group. J. Clin. Oncol. 1999;17:2341–2354
  84. Behar A, Pujade-Lauraine E, Maurel A, et al.  The pathophysiological mechanism of fluid retention in advanced cancer patients treated with docetaxel, but not receiving corticosteroid comedication. Br. J. Clin. Pharmacol. 1997;43:653–658
  85. Semb KA, Aamdal S, Oian P. Capillary protein leak syndrome appears to explain fluid retention in cancer patients who receive docetaxel treatment. J. Clin. Oncol. 1998;16:3426–3432
  86. Verweij J, Clavel M, Chevalier B. Paclitaxel (Taxol) and docetaxel (Taxotere): not simply two of a kind. Ann. Oncol. 1994;5:495–505
  87. Bocci G, Nicolaou KC, Kerbel RS. Protracted low-dose effects on human endothelial cell proliferation and survival in vitro reveal a selective antiangiogenic window for various chemotherapeutic drugs. Cancer Res. 2002;62:6938–6943
  88. Wang J, Lou P, Lesniewski R, Henkin J. Paclitaxel at ultra low concentrations inhibits angiogenesis without affecting cellular microtubule seembly. Anticancer Drugs. 2003;14:13–19
  89. Hayot C, Farinelle S, De Decker R, et al.  In vitro pharmacological characterizations of the anti-angiogenic and anti-tumor cell migration properties mediated by microtubule-affecting drugs, with special emphasis on the organization of the actin cytoskeleton. Int. J. Oncol. 2002;21:417–425
  90. Axel DI, Kuntert W, Goggelmann C, et al.  Paclitaxel inhibits arterial smooth muscle cell proliferation and migration in vitro and in vivo using local drug delivery. Circulation. 1997;96:636–645
  91. Klauber N, Parangi S, Flynn E, Hamel E, D'Amato RJ. Inhibition of angiogenesis and breast cancer in mice by the microtubule inhibitors 2-methoxyestradiol and taxol. Cancer Res. 1997;57:81–86
  92. Vacca A, Ribatti D, Iurlaro M, et al.  Docetaxel versus paclitaxel for antiangiogenesis. J. Hematother. Stem Cell Res. 2002;11:103–108
  93. Grant DS, Williams TL, Zahaczewsky M, Dicker AP. Comparison of antiangiogenic activities using paclitaxel (Taxol) and docetaxel (Taxotere). Int. J. Cancer. 2003;104:121–129
  94. Garcia-Barros M, Paris F, Cordon-Cardo C, et al.  Tumor response to radiotherapy regulated by endothelial cell apoptosis. Science. 2003;300:1155–1159
  95. Hainsworth JD, Burris HA, Yardley DA, Bradof JE. Weekly docetaxel in the treatment of elderly patients with metastatic breast cancer: a Minnie Pearl Cancer Research Network phase II trial. J. Clin. Oncol. 2001;19:3500–3505
  96. Camps C, Massuti B, Jimenez AM, et al.  Second-line docetaxel administrated every 3 weeks versus weekly in advanced non-small cell lung cancer (NSCLC): A Spanish lung cancer group (SLCG) phase III trial. Proc. Am. Soc. Clin. Oncol. 2003;22:625; [Abstract #2514]
  97. Fountzilas G, Tsavdaridis D, Kalogera-Fountzila A, et al.  Weekly paclitaxel as first-line chemotherapy and trastuzumab in patients with advanced breast cancer. Ann. Oncol. 2001;12:1545–1551
  98. Esteva FJ, Valero V, Booser D, et al.  Phase II study of weekly docetaxel and trastuzumab for patient with HER-2-overexpressing metastatic breast cancer. J. Clin. Oncol. 2002;20:1800–1808
  99. Bertolini F, Paul S, Mancuso P, et al.  Maximum tolerable dose and low-dose metronomic chemotherapy have opposite effects on the mobilization and viability of circulating endothelial progenitor cells. Cancer Res. 2003;63:4346
  100. Mishima K, Mazar AP, Gown A, et al.  A peptide derived from the non-receptor-binding region of urokinase plasminogen activator inhibits glioblastoma growth and angiogenesis in vivo in combination with cisplatin. Proc. Natl. Acad. Sci. USA. 2000;97:8484–8489
  101. Schiller JH, Bittner G. Potentiation of platinum antitumor effects in human lung tumor xenografts by the angiogenesis inhibitor squalamine: effects on tumor neovascularization. Clin. Cancer Res. 1999;5:4287–4294
  102. Bello L, Carabba G, Giussani C, et al.  Low-dose chemotherapy combined with an antiangiogenic drug reduces human glioma growth in vivo. Cancer Res. 2001;61:7501–7506
  103. Colleoni M, Rocca A, Sandri MT, 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;13:73–80
  104. Buckstein R, Crump M, Baruchel S, et al.  High dose celecoxib and low dose cyclophosphamide for relapsed aggressive histology NHL. Proc. Am. Soc. Clin. Oncol. 2003;22:206; [Abstract #827]
  105. Bjarnason GA, Krzyzanowska MK, Knox J, et al.  Phase II trial of continuous low dose cyclophosphamide and celecoxib in patients with progressing advanced renal cell carcinoma (RCC). Proc. Am. Soc. Clin. Oncol. 2003;22:427; [Abstract #1717]
  106. Glode LM, Bargawi A, Crighton F, Crawford ED, Kerbel R. Metronomic therapy with low dose cyclophosphamide and dexamethasone for prostate cancer. Cancer. 2003;98:1643–1648
  107. Kuenen BC, Rosen L, Smit EF, et al.  Dose-finding and pharmacokinetic study of cisplatin, gemcitabine and SU5416 in patients with solid tumors. J. Clin. Oncol. 2002;20:1657–1667
  108. Kuenen BC, Levi M, Meijers JCM, et al.  Analysis of coagulation cascade and endothelial cell activation during inhibition of vascular endothelial growth factor/vascular endothelial growth factor receptor pathway in cancer patients. Arterioscler. Thromb. Vasc. Biol. 2002;22:1500–1505
  109. Marx GM, Steer CB, Harper P, Pavlakis N, Rixe O, Khayat D. Unexpected serious toxicity with chemotherapy and antiangiogenic combinations: time to take stock!. J. Clin. Oncol. 2002;20:1446–1448
  110. Becker K, Erckenbrecht JF, Haussinger D, Frieling T. Cardiotoxicity of the antiproliferative compound fluorouracil. Drugs. 1999;57:475–484
  111. Burger AJ, Mannino S. 5-Fluorouracil-induced coronary vasospasm. Am. Heart J. 1987;114:433–436
  112. Anderson RN, Lokich JJ, Moore C. The syndrome of 5-fluorouracil cardiotoxicity: an elusive cardiopathy. Cancer. 1993;72:2287–2288
  113. de Forni M, Malet-Martino MC, Jaillais P, et al.  Cardiotoxicity of high-dose continuous infusion fluorouracil: a prospective clinical study. J. Clin. Oncol. 1992;10:1795–1801
  114. Grandi AM, Pinotti G, Morandi E, et al.  Non-invasive evaluation of cardiotoxicity of 5-fluorouracil and low doses of folinic acid: a one-year follow-up study. Ann. Oncol. 1997;8:705–708
  115. Millart H, Brabant L, Lorenzato M, Lamiable D, Albert O, Choisy H. The effects of 5-fluorouracil on contractibility and oxygen uptake of the isolated perfused rat heart. Anticancer Res. 1992;12:571–576
  116. Fuskevag OM, Kristiansen C, Olsen R, Aarbakke J, Lindsal S. Microvascular perturbations in rats receiving the maximum tolerated dose of methotrexate or its metabolite 7-hydroxymethotrexate. Ultrastruct. Pathol. 2000;24:325–332
  117. Basaki Y, Chikahisa L, Aoyagi K, et al.  Gamma-hydroxybutyric acid and 5-fluorouracil, metabolites of UFT, inhibit the angiogenesis induced by vascular endothelial growth factor. Angiogenesis. 2001;4:163–173
  118. Cwikiel M, Eskilsson J, Albertsson M, Stavenow L. The influence of 5-fluorouracil and methotrexate on vascular endothelium. An experimental study using endothelial cells culture. Ann. Oncol. 1996;7:731–737
  119. Codacci-Pisanelli G, van der Wilt CL, Pinedo HM, et al.  Anti-tumour activity, toxicity and inhibition of thymidylate synthase of prolonged administration of 5-fluorouracil in mice. Eur. J. Cancer. 1995;31A:1517–1525
  120. Zhou J, Tang ZY, Fan J, et al.  Capacetabine inhibits postoperative recurrence and metastasis after liver cancer resection in nude mice with relation to the expression of platelet-derived endothelial cell growth factor. Clin. Cancer Res. 2003;9:6030–6037
  121. Furukawa T, Yoshimura A, Sumizawa T, et al.  Angiogenic factor. Nature. 1992;356:668
  122. Miyadera K, Sumizawa T, Haraguchi M, et al.  Role of thymidine phosphorylase activity in the angiogenic effect of platelet derived endothelial cell growth factor/thymidine phosphorylase. Cancer Res. 1995;55:1687–1690
  123. Endo M, Shindori N, Fukase Y, et al.  Induction of thymidine phosphorylase expression and enhancement of efficacy of capecitabine or 5-deoxy-5-fluorouridine by cyclophosphamide in mammary tumor models. Int. J. Cancer. 1999;83:127–134
  124. Fujimoto-Ouchi K, Tanaka Y, Tominaga T. Schedule dependency of antitumor activity in combination therapy with capecitabine/5-deoxy-5-fluorouridine and docetaxel in breast cancer models. Clin. Cancer Res. 2001;7:1079–1086
  125. Köhne CH, Wils J, Lorenz M, et al.  Randomized phase III study of high-dose fluorouracil given as a weekly 24-hour infusion with or without leucovorin versus bolus fluorouracil plus leucovorin in advanced colorectal cancer: European Organization of Research and Treatment of Cancer Gastrointestinal Group Study 40952. J. Clin. Oncol. 2003;21:3721–3728
  126. Wolmark N, Piedbois P, Buyse M, Carlson R, Rustum Y, Erlichman C. Efficacy of intravenous continuous infusion of fluorouracil compared with bolus administration in advanced colorectal cancer. J. Clin. Oncol. 1998;16:301–308
  127. Hoff PM, Ansari R, Batist G, et al.  Comparison of oral capecitabine versus intravenous fluorouracil plus leucovorin as first-line treatment in 605 patients with metastatic colorectal cancer: results of a randomized phase III study. J. Clin. Oncol. 2001;19:2282–2292
  128. Van Cutsem E, Twelves CJ, Cassidy J, et al.  Oral capecitabine compared with intravenous fluorouracil plus leucovorin in patients with metastatic colorectal cancer: results of a large phase III study. J. Clin. Oncol. 2001;19:4097–4106
  129. Twelves C on behalf of the Xeloda Colorectal Cancer Group. Capecitabine as first-line treatment in colorectal cancer: pooled data from two large, phase III trials. Eur J Cancer 2002;38:S15–S20
  130. Kabbinavar F, Hurwitz HI, Fehrenbacher L, et al.  Phase II, randomized trial comparing bevacizumab plus fluorouracil (FU)/leucovorin (LV) with FU/LV alone in patients with metastatic colorectal cancer. J. Clin. Oncol. 2003;21:60–65
  131. Giantonio BJ, Levy D, O'Dwyer PJ, Meropol NJ, Catalano PJ, Benson AB. Bevazicumab (anti-VEGF) plus IFL (irinotecan, fluorouracil, leucovorin) as front-line therapy for advanced colorectal cancer (advCRC): results from the Eastern Cooperative Oncology Group (ECOG) study E2200. Proc. Am. Soc. Clin. Oncol. 2003;22:255; [Abstract #1024]
  132. Hurwitz H, Fehrenbacher L, Cartwright T, et al.  Bevacizumab (a monoclonal antibody to vascular endothelial growth factor) prolongs survival in first-line colorectal cancer (CRC): results of a phase II trial of bevacizumab in combination with bolus IFL (irinotecan, 5-fluorouracil, leucovorin) as first-line therapy in subjects with metastatic CRC. Proc. Am. Soc. Clin. Oncol. 2003;22: [Abstract #3646]
  133. Singal PK, Iliskovic N. Doxorubicin-induced cardiomyopathy. N. Engl. J. Med. 1998;339:900–905
  134. Shapiro CL, Hardenbergh PH, Gelman R, et al.  Cardiac effects of adjuvant doxorubicin and radiation therapy in breast cancer patients. J. Clin. Oncol. 1998;16:3493–3501
  135. Kalivendi SV, Kotamraju S, Zhao H, Joseph J, Kalyanaraman B. Doxorubicin-induced apoptosis is associated with increased transcription of endothelial nitric-oxide synthase. Effect of antiapoptotic antioxidants and calcium. J. Biol. Chem. 2001;276:47266–47276
  136. Vasquez-Vivar J, Martasek P, Hogg N, Masters BS, Pritchard KA, Kalyanaraman B. Endothelial nitric oxide synthase-dependent superoxide generation from adriamycin. Biochemistry. 1997;36:11293–11297
  137. Mailloux A, Grenet K, Bruneel A, Beneteau-Burnat B, Vaubourdolle M, Baudin B. Anticancer drugs induce necrosis of human endothelial cells involving both oncosis and apoptosis. Eur. J. Cell Biol. 2001;80:442–449
  138. Plum SM, Hanson AD, Volker KM, et al.  Synergistic activity of recombinant human endostatin in combination with adriamycin: analysis of in vitro activity on endothelial cells and in vivo tumor progression in an orthotropic murine mammary carcinoma model. Clin. Cancer Res. 2003;9:4619–4626
  139. Zhang L, Yu D, Hicklin DJ, Hannay JA, Ellis LM, Pollock RE. Combined anti-fetal liver kinase 1 monoclonal antibody and continuous low-dose doxorubicin inhibits angiogenesis and growth of human soft tissue sarcoma xenografts by introduction of endothelial cell apoptosis. Cancer Res. 2002;62:2034–2042
  140. Klement G, Huang P, Mayer B, et al.  Differences in therapeutic indexes of combination metronomic chemotherapy and an anti-VEGFR-2 antibody in multidrug-resistant human breast cancer xenografts. Clin. Cancer Res. 2002;8:221–232
  141. Richards MA, Hopwood P, Ramirez AJ, et al.  Doxorubicin in advanced breast cancer: influence of schedule on response, survival and quality of life. Eur. J. Cancer. 1992;28A:1023–1028
  142. Bielack SS, Erttmann R, Winkler K, Landbeck G. Doxorubicin: effect of different schedules on toxicity and anti-tumor efficacy. Eur. J. Cancer Clin. Oncol. 1989;25:873–882
  143. Hortobagyi GN, Frye D, Buzdar AU, et al.  Decreased cardiac toxicity of doxorubicin administered by continuous intravenous infusion in combination chemotherapy for metastatic breast cancer. Cancer. 1989;63:37–45
  144. Allegrini G, Goulette FA, Darnowski JW, Calabresi P. Thrombospondin-1 plus irinotecan: a novel antiangiogenic-chemotherapeutic combination that inhibits the growth of advanced human colon tumor xenografts in mice. Cancer Chemother. Pharmacol. 2004;27:101–105
  145. Dings RP, Yokoyama Y, Ramakrishnan S, Griffioen AW, Mayo KH. The designed angiostatic peptide anginex synergistically improves chemotherapy and anti-angiogenesis therapy with angiostatin. Cancer Res. 2003;63:382–385
  146. Mauceri HJ, Seetharam S, Beckett MA, et al.  Angiostatin potentiates cyclophosphamide treatment of metastatic disease. Cancer Chemother. Pharmacol. 2002;50:412–418
  147. Steward WP, Thomas AL, Morgan B, et al.  Extended phase I study of the oral vascular endothelial growth factor (VEGF) receptor inhibitor PTK787/ZK222584 in combination with oxaliplatin/5-fluorouracil (5-FU)/leucovorin as first line treatment for metastatic colorectal cancer. Proc. Am. Soc. Clin. Oncol. 2003;22:274; [Abstract #1098]
  148. Capizzi RL, Oster W. Chemoprotective and radioprotective effects of amifostine: an update of clinical trials. Int. J. Hematol. 2000;72:425–435
  149. Mertsch K, Grune T, Kunstmann S, et al.  Protective effects of the thiophosphate amifostine (WR2721) and a lazaroid (U83836E) on lipid peroxidation in endothelial cells during hypoxia/reoxygenation. Biochem. Pharmacol. 1998;56:945–954
  150. Giannopoulou E, Katsoris P, Kardamakis D, Papdimitriou E. Amifostine inhibits angiogenesis in vivo. J. Pharmacol. Exp. Ther. 2003;304:729–737
  151. Schuchter LM, Hensley ML, Meropol NJ, Winer EP. 2002 update of recommendations for the use of chemotherapy and radiotherapy protectants: clinical practice guidelines of the American Society of Clinical Oncology. J. Clin. Oncol. 2002;20:2895–2903
  152. Kemp G, Rose P, Lurain J, et al.  Amifostine pretreatment for protection against cyclophosphamide-induced and cisplatin-induced toxicities: results of a randomized control trial in patients with advanced ovarian cancer. J. Clin. Oncol. 1996;14:2101–2112
  153. Weijl NI, Elsendoorn TJ, Moison RMW, et al.  Non-protein bound iron release during chemotherapy in cancer patients. Clin. Sci. 2004;106:475–484
  154. Elsendoorn TJ, Weijl NI, Mithoe S, et al.  Chemotherapy-induced chromosomal damage in peripheral blood lymphocytes of cancer patients supplemented with antioxidants or placebo. Mutat. Res. 2001;498:145–158
  155. de Vos FY, Hoekstra R, Eskens FA, et al.  Dose–finding and pharmacokinetic study of ABT–510 with germcitabine and cisplatin in patients with advanced cancer. Proc. Am. Soc. Clin. Oncol. 2004;23:214; (#3077)

PII: S0305-7372(04)00095-7

doi: 10.1016/j.ctrv.2004.05.003

Cancer Treatment Reviews
Volume 30, Issue 6 , Pages 495-513 , October 2004