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Drugs Affecting Growth of Tumours pp 83–100Cite as

Topoisomerase inhibitors

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Part of the book series: Milestones in Drug Therapy ((MDT))

Abstract

DNA topoisomerase inhibitors, known for their broad antitumour activity, represent one of the most widely used groups of anticancer agents. In spite of the early discovery and long-standing clinical use, the mechanism of action of these agents was not recognized until the 1980s [1–3].

Currently agents available for clinical use include the topoisomerase I inhibitors of the camptothecin class (topotecan and irinotecan) and the topoisomerase II inhibitors in the class of epipodophyllotoxins (etoposide and teniposide). Many new formulations and structurally-related agents are currently undergoing clinical development. This chapter highlights the most important aspects of the past, current and future development of topoisomerase I and II inhibitors, and provides an overview of pharmacology and clinical data, with a focus on recent developments.

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References

  1. Hsiang YH, Liu LF (1988) Identification of mammalian DNA topoisomerase-I as an intracellular target of the anticancer drug camptothecin. Cancer Res 48(7): 1722–1726

    PubMed  CAS  Google Scholar 

  2. Nelson EM, Tewey KM, Liu LF (1984) Mechanism of antitumor drug-action — poisoning of mammalian DNA topoisomerase-II on DNA by 4′-(9-acridinylamino)-methanesulfon-meta-anisidide. Proc Natl Acad Sci USA 81(5): 1361–1365

    Article  PubMed  CAS  Google Scholar 

  3. Tewey KM, Chen GL, Nelson EM, Liu LF (1984) Intercalative antitumor drugs interfere with the breakage-reunion reaction of mammalian DNA topoisomerase-II. J Biol Chem 259(14):9182–9187

    PubMed  CAS  Google Scholar 

  4. Osheroff N, Zechiedrich EL, Gale KC (1991) Catalytic function of DNA topoisomerase-II. Bioessays 13(6): 269–275

    Article  PubMed  CAS  Google Scholar 

  5. Wang JC (2002) Cellular roles of DNA topoisomerases: A molecular perspective. Nat Rev Mol Cell Biol 3(6): 430–440

    Article  PubMed  CAS  Google Scholar 

  6. Walker JV, Nitiss JL (2002) DNA topoisomerase II as a target for cancer chemotherapy. Cancer Invest 20(4): 570–589

    Article  PubMed  CAS  Google Scholar 

  7. de Jonge MJA, Sparreboom A, Verweij J (1998) The development of combination therapy involving camptothecins: a review of preclinical and early clinical studies. Cancer Treat Rev 24(3):205–220

    Article  PubMed  Google Scholar 

  8. Wall ME, Wani MC, Cook CE, Palmer KH, Mcphail AT, Sim GA (1966) Plant antitumor agents. I. Isolation and structure of camptothecin. A novel alkaloidal leukemia and tumor inhibitor from Camptotheca Acuminata. J Am Chem Soc 88(16): 3889–3890

    Article  Google Scholar 

  9. Moertel CG, Schutt AJ, Reitemei RJ, Hahn RG (1972) Phase II study of camptothecin (NSC-100880) in treatment of advanced gastrointestinal cancer. Cancer Chemother Rep Part 1 56(1):95–101

    PubMed  CAS  Google Scholar 

  10. Creaven PJ, Allen LM (1972) Camptothecin plasma levels during a 5-day course — Correlation with toxicity. Proc AACR 13: 46

    Google Scholar 

  11. Gottlieb JA, Guarino AM, Oliverio VT, Block JB (1970) Preliminary clinical and pharmacological studies with camptothecin sodium (Cs). Proc AACR 11: 31

    Google Scholar 

  12. Muggia FM, Cohen MH, Hansen HH, Creaven PJ, Selawry OS (1972) Phase I clinical trial of weekly and daily treatment with camptothecin (NSC-100880) — Correlation with preclinical studies. Cancer Chemother Rep Part 1 56(4): 515–521

    PubMed  CAS  Google Scholar 

  13. Hsiang YH, Hertzberg R, Hecht S, Liu LF (1985) Camptothecin induces protein-linked DNA breaks via mammalian DNA topoisomerase-I. J Biol Chem 260(27): 4873–4878

    Google Scholar 

  14. Giovanella BC, Stehlin JS, Wall ME, Wani MC, Nicholas AW, Liu LF et al. (1989) DNA topoisomerase-I targeted chemotherapy of human-colon cancer in xenografts. Science 246(4933):1046–1048

    Article  PubMed  CAS  Google Scholar 

  15. van der Zee AGJ, Hollema H, de Jong S, Boonstra H, Gouw A, Willemse PHB et al. (1991) P-glycoprotein expression and DNA topoisomerase-I and topoisomerase-II activity in benign-tumors of the ovary and in malignant-tumors of the ovary, before and after platinum cyclophosphamide chemotherapy. Cancer Res 51(21): 5915–5920

    PubMed  Google Scholar 

  16. Burris HA, Hanauske AR, Johnson RK, Marshall MH, Kuhn JG, Hilsenbeck SG et al. (1992) Activity of topotecan, a new topoisomerase-I inhibitor, against human tumor colony-forming-units in vitro. J Natl Cancer Inst 84(23): 1816–1820

    Article  PubMed  CAS  Google Scholar 

  17. Daoud SS, Fetouh MI, Giovanella BC (1995) Antitumor effect of liposome-incorporated camptothecin in human-malignant xenografts. Anti-Cancer Drugs 6(1): 83–93

    Article  PubMed  CAS  Google Scholar 

  18. Giovanella BC, Hinz HR, Kozielski AJ, Stehlin JS, Silber R, Potmesil M (1991) Complete growth-inhibition of human cancer xenografts in nude-mice by treatment with 20-(S)-camptothecin. Cancer Res 51(11): 3052–3055

    PubMed  CAS  Google Scholar 

  19. Houghton PJ, Cheshire PJ, Myers L, Stewart CF, Synold TW, Houghton JA (1992) Evaluation of 9-dimethylaminomethyl-10-hydroxycamptothecin against xenografts derived from adult and childhood solid tumors. Cancer Chemother Pharmacol 31(3): 229–239

    Article  PubMed  CAS  Google Scholar 

  20. Houghton PJ, Cheshire PJ, Hallman JD, Lutz L, Friedman HS, Danks MK et al. (1995) Efficacy of topoisomerase-I inhibitors, topotecan and irinotecan, administered at low-dose levels in protracted schedules to mice bearing xenografts of human tumors. Cancer Chemother Pharmacol 36(5): 393–403

    PubMed  CAS  Google Scholar 

  21. Pantazis P, Hinz HR, Mendoza JT, Kozielski AJ, Williams LJ, Stehlin JS et al. (1992) Complete inhibition of growth followed by death of human-malignant melanoma-cells in vitro and regression of human-melanoma xenografts in immunodeficient mice induced by camptothecins. Cancer Res 52(14): 3980–3987

    PubMed  CAS  Google Scholar 

  22. Pantazis P, Kozielski A, Rodriguez R, Petry E, Wani M, Wall M et al. (1994) Therapeutic efficacy of camptothecin derivatives against human-malignant melanoma xenografts. Melanoma Res 4(1): 5–10

    Article  PubMed  CAS  Google Scholar 

  23. Hochster H, Liebes L, Speyer J, Sorich J, Taubes B, Oratz R et al. (1994) Phase-I trial of low-dose continuous topotecan infusion in patients with cancer — An active and well-tolerated regimen. J Clin Oncol 12(3): 553–559

    PubMed  CAS  Google Scholar 

  24. Hochster H, Liebes L, Speyer J, Sorich J, Taubes B, Oratz R et al. (1997) Effect of prolonged topotecan infusion on topoisomerase 1 levels: A phase I and pharmacodynamic study. Clin Cancer Res 3(8): 1245–1252

    PubMed  CAS  Google Scholar 

  25. Stevenson JP, Scher RM, Kosierowski R, Fox SC, Simmonds M, Yao KS et al. (1998) Phase II trial of topotecan as a 21-day continuous infusion in patients with advanced or metastatic adenocarcinoma of the pancreas. Eur J Cancer 34(9): 1358–1362

    Article  PubMed  CAS  Google Scholar 

  26. Herben VMM, ten Bokkel Huinink WW, Schot ME, Hudson I, Beijnen JH (1998) Continuous infusion of low-dose topotecan: pharmacokinetics and pharmacodynamics during a phase II study in patients with small cell lung cancer. Anti-Cancer Drugs 9(5): 411–418

    Article  PubMed  CAS  Google Scholar 

  27. Herben VMM, Schellens JHM, Swart M, Gruia G, Vernillet L, Beijnen JH et al. (1999) Phase I and pharmacokinetic study of irinotecan administered as a low-dose, continuous intravenous infusion over 14 days in patients with malignant solid tumors. J Clin Oncol 17(6): 1897–1905

    PubMed  CAS  Google Scholar 

  28. Kindler HL, Kris MG, Smith IE, Miller VA, Grant SC, Krebs JB et al. (1998) Phase II trial of topotecan administered as a 21-day continuous infusion in previously untreated patients with stage IIIB and IV non-small-cell lung cancer. Am J Clin Oncol 21(5): 438–441

    Article  PubMed  CAS  Google Scholar 

  29. Creemers GJ, Gerrits CJH, Schellens JHM, Planting AST, van der Burg MEL, van Beurden VM et al. (1996) Phase II and pharmacologic study of topotecan administered as a 21-day continuous infusion to patients with colorectal cancer. J Clin Oncol 14(9): 2540–2545

    PubMed  CAS  Google Scholar 

  30. Kingsbury WD, Boehm JC, Jakas DR, Holden KG, Hecht SM, Gallagher G et al. (1991) Synthesis of water-soluble (aminoalkyl)camptothecin analogs — inhibition of topoisomerase-I and antitumor-activity. J Med Chem 34(1): 98–107

    Article  PubMed  CAS  Google Scholar 

  31. Schellens JHM, Creemers GJ, Beijnen JH, Rosing H, de Boer-Dennert M, McDonald M et al. (1996) Bioavailability and pharmacokinetics of oral topotecan: A new topoisomerase I inhibitor. Br J Cancer 73(10): 1268–1271

    PubMed  CAS  Google Scholar 

  32. Kruijtzer CMF, Beijnen JH, Rosing H, ten Bokkel Huinink WW, Schot M, Jewell RC et al. (2002) Increased oral bioavailability of topotecan in combination with the breast cancer resistance protein and P-glycoprotein inhibitor GF120918. J Clin Oncol 20(13): 2943–2950

    Article  PubMed  CAS  Google Scholar 

  33. O’Reilly S, Rowinsky EK, Slichenmyer W, Donehower RC, Forastiere AA, Ettinger DS et al. (1996) Phase I and pharmacologic study of topotecan in patients with impaired renal function. J Clin Oncol 14(12): 3062–3073

    PubMed  CAS  Google Scholar 

  34. O’Reilly S, Rowinsky E, Slichenmyer W, Donehower RC, Forastiere A, Ettinger D et al. (1996) Phase I and pharmacologic studies of topotecan in patients with impaired hepatic function. J Natl Cancer Inst 88(12): 817–824

    Article  PubMed  CAS  Google Scholar 

  35. Gelderblom H, Loos WJ, Verweij J, de Jonge MJA, Sparreboom A (2000) Topotecan lacks third space sequestration. Clin Cancer Res 6(4): 1288–1292

    PubMed  CAS  Google Scholar 

  36. Baker SD, Heideman RL, Crom WR, Kuttesch JF, Gajjar A, Stewart CF (1996) Cerebrospinal fluid pharmacokinetics and penetration of continuous infusion topotecan in children with central nervous system tumors. Cancer Chemother Pharmacol 37(3): 195–202

    Article  PubMed  CAS  Google Scholar 

  37. Kim JH, Kim SH, Kolozsvary A, Khil MS (1992) Potentiation of radiation response in human carcinoma-cells in vitro and murine fibrosarcoma in vivo by topotecan, an inhibitor of DNA topoisomerase-I. Int J Radiat Oncol Biol Phys 22(3): 515–518

    PubMed  CAS  Google Scholar 

  38. Loos WJ, Gelderblom H, Sparreboom A, Verweij J, de Jonge MJA (2000) Inter-and intrapatient variability in oral topotecan pharmacokinetics: Implications for body-surface area dosage regimens. Clin Cancer Res 6(7): 2685–2689

    PubMed  CAS  Google Scholar 

  39. Grochow LB, Rowinsky EK, Johnson R, Ludeman S, Kaufmann SH, McCabe FL et al. (1992) Pharmacokinetics and pharmacodynamics of topotecan in patients with advanced cancer. Drug Metab Dispos 20(5): 706–713

    PubMed  CAS  Google Scholar 

  40. Rowinsky EK, Adjei A, Donehower RC, Gore SD, Jones RJ, Burke PJ et al. (1994) Phase-I and pharmacodynamic study of the topoisomerase I-inhibitor topotecan in patients with refractory acute-leukemia. J Clin Oncol 12(10): 2193–2203

    PubMed  CAS  Google Scholar 

  41. van Warmerdam LJC, Verweij J, Schellens JHM, Rosing H, Davies BE, de Boer-Dennert M et al. (1995) Pharmacokinetics and pharmacodynamics of topotecan administered daily for 5 days every 3 weeks. Cancer Chemother Pharmacol 35(3): 237–245

    Article  PubMed  Google Scholar 

  42. Gallo JM, Laub PB, Rowinsky EK, Grochow LB, Baker SD (2000) Population pharmacokinetic model for topotecan derived from phase I clinical trials. J Clin Oncol 18(12): 2459–2467

    PubMed  CAS  Google Scholar 

  43. Montazeri A, Boucaud M, Lokiec F, Pinguet F, Culine S, Deporte-Fety R et al. (2000) Population pharmacokinetics of topotecan: intraindividual variability in total drug. Cancer Chemother Pharmacol 46(5): 375–381

    Article  PubMed  CAS  Google Scholar 

  44. Montazeri A, Culine S, Laguerre B, Pinguet F, Lokiec FO, Albin N et al. (2002) Individual adaptive dosing of topotecan in ovarian cancer. Clin Cancer Res 8(2): 394–399

    PubMed  CAS  Google Scholar 

  45. Leger F, Loos WJ, Fourcade J, Bugat R, Goffinet M, Mathijssen RHJ et al. (2004) Factors affecting pharmacokinetic variability of oral topotecan: a population analysis. Br J Cancer 90(2):343–347

    Article  PubMed  CAS  Google Scholar 

  46. ten Bokkel Huinink WW, Gore M, Carmichael J, Gordon A, Malfetano J, Hudson I et al. (1997) Topotecan versus paclitaxel for the treatment of recurrent epithelial ovarian cancer. J Clin Oncol 15(6): 2183–2193

    PubMed  Google Scholar 

  47. McGuire WP, Blessing JA, Bookman MA, Lentz SS, Dunton CJ (2000) Topotecan has substantial antitumor activity as first-line salvage therapy in platinum-sensitive epithelial ovarian carcinoma: A Gynecologic Oncology Group study. J Clin Oncol 18(5): 1062–1067

    PubMed  CAS  Google Scholar 

  48. Gordon AN, Fleagle JT, Guthrie D, Parkin DE, Gore ME, Lacave AJ (2001) Recurrent epithelial ovarian carcinoma: A randomized phase III study of pegylated liposomal doxorubicin versus topotecan. J Clin Oncol 19(14): 3312–3322

    PubMed  CAS  Google Scholar 

  49. Gore M, Oza A, Rustin G, Malfetano J, Calvert H, Clarke-Pearson D et al. (2002) A randomised trial of oral versus intravenous topotecan in patients with relapsed epithelial ovarian cancer. Eur J Cancer 38(1): 57–63

    Article  PubMed  CAS  Google Scholar 

  50. Schiller JH, Kim KM, Hutson P, DeVore R, Glick J, Stewart J et al. (1996) Phase II study of topotecan in patients with extensive-stage small-cell carcinoma of the lung: An Eastern Cooperative Oncology Group trial. J Clin Oncol 14(8): 2345–2352

    PubMed  CAS  Google Scholar 

  51. Ardizzoni A, Hansen H, Dombernowsky P, Gamucci T, Kaplan S, Postmus P et al. (1997) Topotecan, a new active drug in the second-line treatment of small-cell lung cancer: A phase II study in patients with refractory and sensitive disease. J Clin Oncol 15(5): 2090–2096

    PubMed  CAS  Google Scholar 

  52. von Pawel J, Schiller JH, Shepherd FA, Fields SZ, Kleisbauer JP, Chrysson NG et al. (1999) Topotecan versus cyclophosphamide, doxorubicin, and vincristine for the treatment of recurrent small-cell lung cancer. J Clin Oncol 17(2): 658–667

    Google Scholar 

  53. Schiller JH, Adak S, Cella D, Devore RF, Johnson DH (2001) Topotecan versus observation after cisplatin plus etoposide in extensive-stage small-cell lung cancer: E7593 — A phase III trial of the Eastern Cooperative Oncology Group. J Clin Oncol 19(8): 2114–2122

    PubMed  CAS  Google Scholar 

  54. von Pawel J, Gatzemeier U, Pujol JL, Moreau L, Bildat S, Ranson M et al. (2001) Phase II comparator study of oral versus intravenous topotecan in patients with chemosensitive small-cell lung cancer. J Clin Oncol 19(6): 1743–1749

    Google Scholar 

  55. Beran M, Kantarjian H, OBrien S, Koller C, AlBitar M, Arbuck S et al. (1996) Topotecan, a topoisomerase I inhibitor, is active in the treatment of myelodysplastic syndrome and chronic myelomonocytic leukemia. Blood 88(7): 2473–2479

    PubMed  CAS  Google Scholar 

  56. Beran M, Kantarjian H, OBrien S, Koller C, AlBitar M, Arbuck S et al. (1996) Topotecan, a topoisomerase I inhibitor, is active in the treatment of myelodysplastic syndrome and chronic myelomonocytic leukemia. Blood 88(7): 2473–2479

    PubMed  CAS  Google Scholar 

  57. Kantarjian HM, Beran M, Ellis A, Zwelling L, Obrien S, Cazenave L et al. (1993) Phase-I study of topotecan, a new topoisomerase-I inhibitor, in patients with refractory or relapsed acuteleukemia. Blood 81(5): 1146–1151

    PubMed  CAS  Google Scholar 

  58. Rowinsky EK, Adjei A, Donehower RC, Gore SD, Jones RJ, Burke PJ et al. (1994) Phase-I and pharmacodynamic study of the topoisomerase I-inhibitor topotecan in patients with refractory acute-leukemia. J Clin Oncol 12(10): 2193–2203

    PubMed  CAS  Google Scholar 

  59. Rowinsky EK, Kaufmann SH, Baker SD, Miller CB, Sartorius SE, Bowling MK et al. (1996) A Phase I and pharmacological study of topotecan infused over 30 minutes for five days in patients with refractory acute leukemia. Clin Cancer Res 2(12): 1921–1930

    PubMed  CAS  Google Scholar 

  60. Beran M, O’Brien S, Thomas DA, Tran HT, Cortes-Franco JE, Giles F et al. (2003) Phase I study of oral topotecan in hematological malignancies. Clin Cancer Res 9(11): 4084–4091

    PubMed  CAS  Google Scholar 

  61. Crump M, Couban S, Meyer R, Rudinskas L, Zanke B, Gluck S et al. (2002) Phase II study of sequential topotecan and etoposide in patients with intermediate grade non-Hodgkin’s lymphoma: A National Cancer Institute of Canada Clinical Trials Group study. Leuk Lymphoma 43(8):1581–1587

    Article  PubMed  CAS  Google Scholar 

  62. Kraut EH, Balcerzak SP, Young D, Davis MP, Jacobs SA (2002) A phase II study of topotecan in non-Hodgkin’s lymphoma: An Ohio State University phase II research consortium study. Cancer Invest 20(2): 174–179

    Article  PubMed  CAS  Google Scholar 

  63. Bookman MA, Blessing JA, Hanjani P, Herzog TJ, Andersen WA (2000) Topotecan in squamous cell carcinoma of the cervix: A phase II study of the gynecologic oncology group. Gynecol Oncol 77(3): 446–449

    Article  PubMed  CAS  Google Scholar 

  64. Muderspach LI, Blessing JA, Levenback C, Moore JL (2001) A Phase II study of topotecan in patients with squamous cell carcinoma of the cervix: A gynecologic oncology group study. Gynecol Oncol 81(2): 213–215

    Article  PubMed  CAS  Google Scholar 

  65. Fiorica J, Holloway R, Ndubisi B, Orr J, Grendys E, Boothby R et al. (2002) Phase II trial of topotecan and cisplatin in persistent or recurrent squamous and nonsquamous carcinomas of the cervix. Gynecol Oncol 85(1): 89–94

    Article  PubMed  CAS  Google Scholar 

  66. Fiorica JV (2003) The role of topotecan in the treatment of advanced cervical cancer. Gynecol Oncol 90(3): S16–S21

    Article  PubMed  CAS  Google Scholar 

  67. Rose PG, Gordon NH, Fusco N, Fluellen L, Rodriguez M, Ingalls ST et al. (2000) A phase II and pharmacokinetic study of weekly 72-h topotecan infusion in patients with platinum-resistant and paclitaxel-resistant ovarian carcinoma. Gynecol Oncol 78(2): 228–234

    Article  PubMed  CAS  Google Scholar 

  68. Wadler S, Levy DE, Lincoln ST, Soori GS, Schink JC, Goldberg G (2003) Topotecan is an active agent in the first-line treatment of metastatic or recurrent endometrial carcinoma: Eastern cooperative oncology group study E3E93. J Clin Oncol 21(11): 2110–2114

    Article  PubMed  CAS  Google Scholar 

  69. Perez Soler R, Fossella FV, Glisson BS, Lee JS, Murphy WK, Shin DM et al. (1996) Phase II study of topotecan in patients with advanced non-small-cell lung cancer previously untreated with chemotherapy. J Clin Oncol 14(2): 503–513

    PubMed  CAS  Google Scholar 

  70. Kindler HL, Kris MG, Smith IE, Miller VA, Grant SC, Krebs JB et al. (1998) Phase II trial of topotecan administered as a 21-day continuous infusion in previously untreated patients with stage IIIB and IV non-small-cell lung cancer. Am J Clin Oncol 21(5): 438–441

    Article  PubMed  CAS  Google Scholar 

  71. Morton CL, Wadkins RM, Danks MK, Potter PM (1999) The anticancer prodrug CPT-11 is a potent inhibitor of acetylcholinesterase but is rapidly catalyzed to SN-38 by butyrylcholinesterase. Cancer Res 59(7): 1458–1463

    PubMed  CAS  Google Scholar 

  72. Kawato Y, Aonuma M, Hirota Y, Kuga H, Sato K (1991) Intracellular roles of Sn-38, a metabolite of the camptothecin derivative CPT-11, in the antitumor effect of CPT-11. Cancer Res 51(16):4187–4191

    PubMed  CAS  Google Scholar 

  73. Tsuji T, Kaneda N, Kado K, Yokokura T, Yoshimoto T, Tsuru D (1991) Cpt-11 converting enzyme from rat serum — purification and some properties. J Pharmacobio-Dynamics 14(6): 341–349

    CAS  Google Scholar 

  74. Zamboni WC, Houghton PJ, Thompson J, Cheshire PJ, Hanna SK, Richmond LB et al. (1998) Altered irinotecan and SN-38 disposition after intravenous and oral administration of irinotecan in mice bearing human neuroblastoma xenografts. Clin Cancer Res 4(2): 455–462

    PubMed  CAS  Google Scholar 

  75. Atsumi R, Okazaki O, Hakusui H (1995) Metabolism of irinotecan to SN-38 in a tissue-isolated tumor-model. Biol Pharm Bull 18(7): 1024–1026

    PubMed  CAS  Google Scholar 

  76. Herben VMM, Schellens JHM, Swart M, Gruia G, Vernillet L, Beijnen JH et al. (1999) Phase I and pharmacokinetic study of irinotecan administered as a low-dose, continuous intravenous infusion over 14 days in patients with malignant solid tumors. J Clin Oncol 17(6): 1897–1905

    PubMed  CAS  Google Scholar 

  77. Mathijssen RHJ, van Alphen RJ, Verweij J, Loos WJ, Nooter K, Stoter G et al. (2001) Clinical pharmacokinetics and metabolism of irinotecan (CPT-11). Clin Cancer Res 7(8): 2182–2194

    PubMed  CAS  Google Scholar 

  78. Rivory LP, Robert J (1995) Identification and kinetics of a beta-glucuronide metabolite of SN-38 in human plasma after administration of the camptothecin derivative irinotecan. Cancer Chemother Pharmacol 36(2): 176–179

    PubMed  CAS  Google Scholar 

  79. Rivory LP, Riou JF, Haaz MC, Sable S, Vuilhorgne M, Commercon A et al. (1996) Identification and properties of a major plasma metabolite of irinotecan (CPT-11) isolated from the plasma of patients. Cancer Res 56(16): 3689–3694

    PubMed  CAS  Google Scholar 

  80. Dodds HM, Haaz MC, Riou JF, Robert J, Rivory LP (1998) Identification of a new metabolite of CPT-11 (irinotecan): Pharmacological properties and activation to SN-38. J Pharmacol Exp Ther 286(1): 578–583

    PubMed  CAS  Google Scholar 

  81. de Bruijn P, Verweij J, Loos WJ, Nooter K, Stoter G, Sparreboom A (1997) Determination of irinotecan (CPT-11) and its active metabolite SN-38 in human plasma by reversed-phase high-performance liquid chromatography with fluorescence detection. J Chromatogr B Biomed Appl 698(1–2): 277–285

    Article  Google Scholar 

  82. Sparreboom A, de Bruijn P, de Jonge MJA, Loos WJ, Nooter K, Stoter G et al. (1998) Liquid chromatographic determination of irinotecan (CPT-11) and its major metabolites in human plasma, urine and feces. Ann Oncol 9: 58

    Google Scholar 

  83. Sparreboom A, de Jonge MJA, de Bruijn P, Brouwer E, Nooter K, Loos WJ et al. (1998) Irinotecan (CPT-11) metabolism and disposition in cancer patients. Clin Cancer Res 4(11):2747–2754

    PubMed  CAS  Google Scholar 

  84. Raymond E, Boige V, Faivre S, Sanderink GJ, Rixe O, Vernillet L et al. (2002) Dosage adjustment and pharmacokinetic profile of irinotecan in cancer patients with hepatic dysfunction. J Clin Oncol 20(21): 4303–4312

    Article  PubMed  CAS  Google Scholar 

  85. Kehrer DFS, Mathijssen RHJ, Verweij J, de Bruijn P, Sparreboom A (2002) Modulation of irinotecan metabolism by ketoconazole. J Clin Oncol 20(14): 3122–3129

    Article  PubMed  CAS  Google Scholar 

  86. Desai AA, Innocenti F, Ratain MJ (2003) UGT pharmacogenomics: implications for cancer risk and cancer therapeutics. Pharmacogenetics 13(8): 517–523

    Article  PubMed  CAS  Google Scholar 

  87. Mathijssen RHJ, Marsh S, Karlsson MO, Xie RJ, Baker SD, Verweij J et al. (2003) Irinotecan pathway genotype analysis to predict pharmacokinetics. Clin Cancer Res 9(9): 3246–3253

    PubMed  CAS  Google Scholar 

  88. Fuchs CS, Moore MR, Harker G, Villa L, Rinaldi D, Hecht JR (2003) Phase III comparison of two irinotecan dosing regimens in second-line therapy of metastatic colorectal cancer. J Clin Oncol 21(5): 807–814

    Article  PubMed  CAS  Google Scholar 

  89. Conti JA, Kemeny NE, Saltz LB, Huang Y, Tong WP, Chou TC et al. (1996) Irinotecan is an active agent in untreated patients with metastatic colorectal cancer. J Clin Oncol 14(3): 709–715

    PubMed  CAS  Google Scholar 

  90. Cunningham D, Pyrhonen S, James RD, Punt CJA, Hickish TF, Heikkila R et al. (1998) Randomised trial of irinotecan plus supportive care versus supportive care alone after fluorouracil failure for patients with metastatic colorectal cancer. Lancet 352(9138): 1413–1418

    Article  PubMed  CAS  Google Scholar 

  91. Rougier P, Van Cutsem E, Bajetta E, Niederle N, Possinger K, Labianca R et al. (1998) Randomised trial of irinotecan versus fluorouracil by continuous infusion after fluorouracil failure in patients with metastatic colorectal cancer. Lancet 352(9138): 1407–1412

    Article  PubMed  CAS  Google Scholar 

  92. Saltz LB, Cox JV, Blanke C, Rosen LS, Fehrenbacher L, Moore MJ et al. (2000) Irinotecan plus fluorouracil and leucovorin for metastatic colorectal cancer. N Engl J Med 343(13): 905–914

    Article  PubMed  CAS  Google Scholar 

  93. Douillard JY, Cunningham D, Roth AD, Navarro M, James RD, Karasek P et al. (2000) Irinotecan combined with fluorouracil compared with fluorouracil alone as first-line treatment for metastatic colorectal cancer: a multicentre randomised trial. Lancet 355(9209): 1041–1047

    Article  PubMed  CAS  Google Scholar 

  94. Rothenberg ML, Meropol NJ, Poplin EA, Van Cutsem E, Wadler S (2001) Mortality associated with irinotecan plus bolus fluorouracil/leucovorin: Summary findings of an independent panel. J Clin Oncol 19(18): 3801–3807

    PubMed  CAS  Google Scholar 

  95. Bajetta E, Di Bartolomeo M, Mariani L, Cassata A, Artale S, Frustaci S et al. (2004) Randomized multicenter phase II trial of two different schedules of irinotecan combined with capecitabine as first-line treatment in metastatic colorectal carcinoma. Cancer 100(2): 279–287

    Article  PubMed  CAS  Google Scholar 

  96. Tournigand C, Andre T, Achille E, Lledo G, Flesh M, Mery-Mignard D et al. (2004) FOLFIRI followed by FOLFOX6 or the reverse sequence in advanced colorectal cancer: A randomized GERCOR study. J Clin Oncol 22(2): 229–237

    Article  PubMed  CAS  Google Scholar 

  97. Rothenberg ML (2001) Irinotecan (CPT-11): recent developments and future directions-colorectal cancer and beyond. Oncologist 6(1): 66–80

    Article  PubMed  CAS  Google Scholar 

  98. Noda W, Nishiwaki Y, Kawahara M, Negoro S, Sugiura T, Yokoyama A et al. (2002) Irinotecan plus cisplatin compared with etoposide plus cisplatin for extensive small-cell lung cancer. N Engl J Med 346(2): 85–91

    Article  PubMed  CAS  Google Scholar 

  99. Saijo N (2003) Progress in treatment of small-cell lung cancer: role of CPT-11. Br J Cancer 89(12): 2178–2183

    Article  PubMed  CAS  Google Scholar 

  100. Negoro S, Masuda N, Takada Y, Sugiura T, Kudoh S, Katakami N et al. (2003) Randomised phase III trial of irinotecan combined with cisplatin for advanced non-small-cell lung cancer. Br J Cancer 88(3): 335–341

    Article  PubMed  CAS  Google Scholar 

  101. Socinski MA, Sandler AB, Israel VK, Gillenwater HH, Miller LL, Locker PK et al. (2002) Phase II trial of irinotecan, paclitaxel and carboplatin in patients with previously untreated stage IIIB/IV nonsmall cell lung carcinoma. Cancer 95(7): 1520–1527

    Article  PubMed  CAS  Google Scholar 

  102. Larsen AK, Eseargueil AE, Skladanowski A (2003) Catalytic topoisomerase II inhibitors in cancer therapy. Pharmacol Ther 99(2): 167–181

    Article  PubMed  CAS  Google Scholar 

  103. Kellner U, Sehested M, Jensen PB, Gieseler F, Rudolph P (2002) Culprit and victim — DNA topoisomerase II. Lancet 3(4): 235–243

    Article  CAS  Google Scholar 

  104. Slevin ML (1991) The clinical-pharmacology of etoposide. Cancer 67(1): 319–329

    Article  PubMed  CAS  Google Scholar 

  105. Hande KR (1998) Etoposide: Four decades of development of a topoisomerase II inhibitor. Eur J Cancer 34(10): 1514–1521

    Article  PubMed  CAS  Google Scholar 

  106. Creaven PJ, Allen LM (1975) EPEG, a new antineoplastic epipodophyllotoxin. Clin Pharmacol Ther 18(2): 221–226

    PubMed  CAS  Google Scholar 

  107. Hande KR, Wolff SN, Greco FA, Hainsworth JD, Reed G, Johnson DH (1990) Etoposide kinetics in patients with obstructive-jaundice. J Clin Oncol 8(6): 1101–1107

    PubMed  CAS  Google Scholar 

  108. Mross K, Bewermeier P, Kruger W, Stockschlader M, Zander A, Hossfeld DK (1994) Pharmacokinetics of undiluted or diluted high-dose etoposide with or without busulfan administered to patients with hematologic malignancies. J Clin Oncol 12(7): 1468–1474

    PubMed  CAS  Google Scholar 

  109. Rodman JH, Murry DJ, Madden T, Santana VM (1994) Altered etoposide pharmacokinetics and time to engraftment in pediatric-patients undergoing autologous bone-marrow transplantation. J Clin Oncol 12(11): 2390–2397

    PubMed  CAS  Google Scholar 

  110. Advani R, Visani G, Milligan D, Saba H, Tallman M, Rowe JM et al. (1999) Treatment of poor prognosis AML patients using PSC833 (valspodar) plus mitoxantrone, etoposide, and cytarabine (PSC-MEC). Drug Resistance in Leukemia and Lymphoma Iii 457: 47–56

    CAS  Google Scholar 

  111. Lum BL, Kaubisch S, Yahanda AM, Adler KM, Jew L, Ehsan MN et al. (1992) Alteration of etoposide pharmacokinetics and pharmacodynamics by cyclosporine in a phase-I trial to modulate multidrug resistance. J Clin Oncol 10(10): 1635–1642

    PubMed  CAS  Google Scholar 

  112. Hande KR, Krozely MG, Greco FA, Hainsworth JD, Johnson DH (1993) Bioavailability of low-dose oral etoposide. J Clin Oncol 11(2): 374–377

    PubMed  CAS  Google Scholar 

  113. Leu BL, Huang JD (1995) Inhibition of intestinal P-glycoprotein and effects on etoposide absorption. Cancer Chemother Pharmacol 35(5): 432–436

    Article  PubMed  CAS  Google Scholar 

  114. Budman DR, Igwemezie LN, Kaul S, Behr J, Lichtman S, Schulman P et al. (1994) Phase-I evaluation of a water-soluble etoposide prodrug, etoposide phosphate, given as a 5-minute infusion on day-1, day-3, and day-5 in patients with solid tumors. J Clin Oncol 12(9): 1902–1909

    PubMed  CAS  Google Scholar 

  115. Kaul S, Igwemezie LN, Stewart DJ, Fields SZ, Kosty M, Levithan N et al. (1995) Pharmacokinetics and bioequivalence of etoposide following intravenous administration of etoposide phosphate and etoposide in patients with solid tumors. J Clin Oncol 13(11):2835–2841

    PubMed  CAS  Google Scholar 

  116. Gelderblom H, Verweij J, Nooter K, Sparreboom A, Cremophor EL (2001) The drawbacks and advantages of vehicle selection for drug formulation. Eur J Cancer 37(13): 1590–1598

    Article  PubMed  CAS  Google Scholar 

  117. Hande KR (1998) Etoposide: four decades of development of a topoisomerase II inhibitor. Eur J Cancer 34(10): 1514–1521

    Article  PubMed  CAS  Google Scholar 

  118. Drewinko B, Barlogie B (1976) Survival and cycle-progression delay of human lymphoma cells in vitro exposed to VP-16-213. Cancer Treat Rep 60(9): 1295–1306

    PubMed  CAS  Google Scholar 

  119. Wolff SN, Grosh WW, Prater K, Hande KR (1987) In vitro pharmacodynamic evaluation of VP-16–213 and implications for chemotherapy. Cancer Chemother Pharmacol 19(3): 246–249

    Article  PubMed  CAS  Google Scholar 

  120. Denny WA, Baguley BC (2003) Dual topoisomerase I/II inhibitors in cancer therapy. Current Topics in Medicinal Chemistry 3(3): 339–353

    Article  PubMed  CAS  Google Scholar 

  121. Clapp JM, Hande KR (2002) Topoisomerase II inhibitors. Cancer Chemother Biol Response Modif 20: 125–149

    PubMed  CAS  Google Scholar 

  122. Valkov NI, Sullivan DM (2003) Tumor p53 status and response to topoisomerase II inhibitors. Drug Resistance Updates 6(1): 27–39

    Article  PubMed  CAS  Google Scholar 

  123. Aisner J, Musanti R, Beers S, Smith S, Locsin S, Rubin EH (2003) Sequencing topotecan and etoposide plus cisplatin to overcome topoisomerase I and II resistance: A pharmacodynamically based phase I trial. Clin Cancer Res 9(7): 2504–2509

    PubMed  CAS  Google Scholar 

  124. Licitra EJ, Vyas V, Nelson K, Musanti R, Beers S, Thomas C et al. (2003) Phase I evaluation of sequential topoisomerase targeting with irinotecan/cisplatin followed by etoposide in patients with advanced malignancy. Clin Cancer Res 9(5): 1673–1679

    PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Clinical Oncology, Leiden University Medical Center, Albinusdreef 2, 2300 RC, Leiden, The Netherlands

    Hans Gelderblom

  2. National Cancer Institute, Bethesda, Maryland, USA

    Alex Sparreboom

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  1. Hans Gelderblom
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  1. Department of Medical Oncology, VU Medical Center, De Bolelaan 1117, 1081 HV, Amsterdam, The Netherlands

    Herbert M. Pinedo  & Carolien H. Smorenburg  & 

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Gelderblom, H., Sparreboom, A. (2006). Topoisomerase inhibitors. In: Pinedo, H.M., Smorenburg, C.H. (eds) Drugs Affecting Growth of Tumours. Milestones in Drug Therapy. Birkhäuser Basel. https://doi.org/10.1007/3-7643-7407-1_3

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