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Clinical Experience With Topotecan

  • Chapter
Camptothecins in Cancer Therapy

Part of the book series: Cancer Drug Discovery and Development ((CDD&D))

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Abstract

Topotecan (Hycamtin, GlaxoSmithKline) is a water-soluble semisynthetic derivative of camptothecin (CPT), an alkaloid extracted from the stem wood of the Chinese tree Camptotheca acuminata (1). As a result of its anticancer activity and favorable toxicity profile, in 1996, topotecan was approved for use in the United States as an antitumor agent in the treatment of recurrent ovarian cancer. In 1998, it was approved as a second-line treatment for patients with small-cell lung cancer (SCLC). Clinical trials have also assessed its activity in the treatment of myelodysplastic syndrome, pancreatic, head and neck, myeloma, prostate, renal cell, melanoma, gliomal, uterine, cervical, hepatocellular, gastric, and breast cancers. Numerous ongoing trials are evaluating the role of topotecan in combination chemotherapy. The current dosing regimen approved by the Food and Drug Administration (FDA) is a 30-minute intravenous (iv) infusion of 1.5 mg/m2 daily for 5 days, which is repeated every 3 weeks. Topotecan is available as a parenteral preparation and is supplied in vials containing 4 mg, which is reconstituted in 4 mL sterile water. The resulting 1 mg/mL solution is further diluted with a 5% dextrose or 0.9% saline solution before injection.

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References

  1. Wall ME, Wani MC, Cook CE, Palmer KH, McPhail AT, Lim GA. 1966 Plant antitumor agents: I. The isolation and structure of camptothecin, a novel alkaloid leukemia and tumor inhibitor from camptotheca accuminata. J Am Chem Soc 88:3888–3890.

    Google Scholar 

  2. Kingsbury WD, Boehm JC, Jakas DR, et al. 1991 Synthesis of water-soluble (aminoalkyl)camptothecin analogues: inhibition of topoisomerase I and antitumor activity. J Med Chem 34:98–107.

    Google Scholar 

  3. Hertzberg RP, Caranfa MJ, Holden KG, et al. 1989 Modification of the hydroxy lactone ring of camptothecin: inhibition of mammalian topoisomerase I and biological activity. J Med Chem 32:715–720.

    Google Scholar 

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

    Google Scholar 

  5. D’Arpa P, Liu LF. 1989 Topoisomerase-targeting antitumor drugs. Biochim Biophys Acta 989: 163–177.

    Google Scholar 

  6. Stewart L, Redinbo MR, Qiu X, Hol WG, Champoux JJ. 1998 A model for the mechanism of human topoisomerase I. Science 279:1534–1541.

    Google Scholar 

  7. Redinbo MR, Stewart L, Kuhn P, Champoux JJ, Hol WG. 1998 Crystal structures of human topoisomerase I in covalent and noncovalent complexes with DNA. Science 279:1504–1513.

    Google Scholar 

  8. Grochow LB, Rowinsky EK, Johnson R, et al. 1992 Pharmacokinetics and pharmacodynamics of topotecan in patients with advanced cancer. Drug Metab Dispos 20:706–713.

    Google Scholar 

  9. van Warmerdam LJ, ten Bokkel Huinink WW, Rodenhuis S, et al. 1995 Phase I clinical and pharmacokinetic study of topotecan administered by a 24-hour continuous infusion. J Clin Oncol 13:1768–1776.

    Google Scholar 

  10. Saylors RL, Stewart CF, Zamboni WC, et al. 1998 Phase I study of topotecan in combination with cyclophosphamide in pediatric patients with malignant solid tumors: a Pediatric Oncology Group Study. J Clin Oncol 16:945–952.

    Google Scholar 

  11. Rowinsky EK, Baker SD, Burks K, O’Reilly S, Donehower RC, Grochow LB. 1998 High-dose topotecan with granulocyte-colony stimulating factor in fluoropyrimidine-refractory colorectal cancer: a phase II and pharmacodynamic study. Ann Oncol 9:173–180.

    Google Scholar 

  12. Saltz L, Sirott M, Young C, et al. 1993 Phase I clinical and pharmacology study of topotecan given daily for 5 consecutive days to patients with advanced solid tumors, with attempt at dose intensification using recombinant granulocyte colonystimulating factor. J Natl Cancer Inst 85:1499–1507.

    Google Scholar 

  13. Wall JG, Burris HA, Von Hoff DD, et al. 1992 A phase I clinical and pharmacokinetic study of the topoisomerase I inhibitor topotecan (SK&F 104864) given as an intravenous bolus every 21 days. Anticancer Drugs 3:337–345.

    Google Scholar 

  14. Haas NB, LaCreta FP, Walczak J, et al. 1994 Phase I/pharmacokinetic study of topotecan by 24-hour continuous infusion weekly. Cancer Res. 54:1220–1226.

    Google Scholar 

  15. Loos WJ, Gelderblom HJ, Verweij J, Brouwer E, de Jonge MJ, Sparreboom A. 2000 Gender-dependent pharmacokinetics of topotecan in adult patients. Anticancer Drugs 11:673–680.

    Google Scholar 

  16. Schellens JH, Creemers GJ, Beijnen JH, et al. 1996 Bioavailability and pharmacokinetics of oral topotecan: a new topoisomerase I inhibitor. Br J Cancer 73: 1268–1271.

    Google Scholar 

  17. Herben VM, Rosing H, ten Bokkel Huinink WW, et al. 1999 Oral topotecan: bioavailablity and effect of food co-administration. Br J Cancer 80:1380–1386.

    Google Scholar 

  18. Kuhn J, Rizzo J, Eckardt J, et al. 1995 Phase I bioavailability study of oral topotecan. Proc Am Soc Clin Oncol 14:474.

    Google Scholar 

  19. Zamboni WC, Bowman LC, Tan M, et al. 1999 Interpatient variability in bioavailability of the intravenous formulation of topotecan given orally to children with recurrent solid tumors. Cancer Chemother Pharmacol 43: 454–460.

    Google Scholar 

  20. Gerrits CJ, Schellens JH, Burris H, et al. 1999 A comparison of clinical pharmacodynamics of different administration schedules of oral topotecan (Hycamtin). Clin Cancer Res 5:69–75.

    Google Scholar 

  21. Rowinsky EK, Grochow LB, Sartorius SE, et al. 1996 Phase I and pharmacologic study of high doses of the topoisomerase I inhibitor topotecan with granulocyte colony-stimulating factor in patients with solid tumors. J Clin Oncol 14:1224–1235.

    Google Scholar 

  22. Rowinsky EK, Grochow LB, Hendricks CB, et al. 1992 Phase I and pharmacologic study of topotecan: a novel topoisomerase I inhibitor. J Clin Oncol 10:647–656.

    Google Scholar 

  23. Tubergen DG, Stewart CF, Pratt CB, et al. 1996 Phase I trial and pharmacokinetic (PK) and pharmacodynamics (PD) study of topotecan using a five-day course in children with refractory solid tumors: a Pediatric Oncology Group Study. J Pediatr Hematol Oncol 18:352–361.

    Google Scholar 

  24. van Warmerdam LJ, Creemers GJ, Rodenhuis S, et al. 1996 Pharmacokinetics and pharmacodynamics of topotecan given on a daily-times-five schedule in phase II clinical trials using a limited-sampling procedure. Cancer Chemother Pharmacol 38:254–260.

    Google Scholar 

  25. Abbruzzese JL, Madden T, Sugarman SM, et al. 1996 Phase I clinical and plasma and cellular pharmacological study of topotecan without and with granulocyte colony-stimulating factor. Clin Cancer Res 2:1489–1497.

    Google Scholar 

  26. Furman WL, Baker SD, Pratt CB, Rivera GK, Evans WE, Stewart CF. 1996 Escalating systemic exposure of continuous infusion topotecan in children with recurrent acute leukemia. J Clin Oncol 14:1504–1511.

    Google Scholar 

  27. Herben VM, ten Bokkel Huinink WW, Beijnen JH. 1996 Clinical pharmacokinetics of topotecan. Clin Pharmacokinet 31:85–102.

    Google Scholar 

  28. Kaye SB, Workman P, Graham MA, Cassidy J, Jodrell D. 1993 Pharmacokinetics and early clinical studies of selected new drugs. Cancer Surv 17:371–396.

    Google Scholar 

  29. El-Gizawy SA, Hedaya MA. 1999 Comparative brain tissue distribution of camptothecin and topotecan in the rat. Cancer Chemother Pharmacol 43:364–370.

    Google Scholar 

  30. Blaney SM, Cole DE, Balis FM, Godwin K, Poplack DG. 1993 Plasma and cerebrospinal fluid pharmacokinetic study of topotecan in nonhuman primates. Cancer Res 53:725–727.

    Google Scholar 

  31. 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 37:195–202.

    Google Scholar 

  32. Rosing H, Herben VM, van Gortel-van Zomeren DM, et al. 1997 Isolation and structural confirmation of N-desmethyl topotecan, a metabolite of topotecan. Cancer Chemother Pharmacol 39:498–504.

    Google Scholar 

  33. Rosing H, van Zomeren DM, Doyle E, et al. 1999 Quantification of topotecan and its metabolite N-desmethyltopotecan in human plasma, urine and faeces by high-performance liquid chromatographic methods. J Chromatogr B Biomed Sci Appl 727:191–203.

    Google Scholar 

  34. Borkowski JM, Duerr M, Donehower RC, et al. 1994 Relation between age and clearance rate of nine investigational anticancer drugs from phase I pharmacokinetic data. Cancer Chemother Pharmacol 33:493–496.

    Google Scholar 

  35. O’Reilly S, Rowinsky E, Slichenmyer W, et al. 1996 Phase I and pharmacologic studies of topotecan in patients with impaired hepatic function. J Natl Cancer Inst 88:817–824.

    Google Scholar 

  36. Armstrong D, O’Reilly S. 1998 Clinical guidelines for managing topotecan-related hematologic toxicity. Oncologist 3:4–10.

    Google Scholar 

  37. Martin D, Hall DJ, Kincaid K. 2003 Phase II trial of weekly topotecan in advanced or recurrent endometrial adenocarcinoma [abstract]. Proc Am Soc Clin Oncol 22:491.

    Google Scholar 

  38. Morris R, Munkarah A. 2002 Alternate dosing schedules for topotecan in the treatment of recurrent ovarian cancer. Oncologist 7(Suppl. 5):29–35.

    Google Scholar 

  39. Homesley HD, Hall DJ, Martin DA, et al. 2001 A dose-escalating study of weekly bolus topotecan in previously treated ovarian cancer patients. Gynecol Oncol 83(2):394–399.

    Google Scholar 

  40. Rocondo G, Abbruzzese J, Newman B, et al. 1991 Phase I trial of topotecan administered by a 24-hour infusion. Proc Am Assoc Cancer Res 32:1229.

    Google Scholar 

  41. Sabiers J, Berger N, Berger S, Haaga JR, Hoppel CR, Wilson JKV. 1993 Phase I trial of topotecan administered as a 72 hour infusion. Proc Am Assoc Cancer Res 34:426.

    Google Scholar 

  42. Rowinsky EK, Adjei A, Donehower RC, et al. 1994 Phase I and pharmacodynamic study of the topoisomerase I-inhibitor topotecan in patients with refractory acute leukemia. J Clin Oncol 12:2193–2203.

    Google Scholar 

  43. Kantarjian HM, Beran M, Ellis A, et al. 1993 Phase I study of topotecan, a new topoisomerase I inhibitor, in patients with refractory or relapsed acute leukemia. Blood 81:1146–1151.

    Google Scholar 

  44. Burris HA, Awada A, Kuhn JG, et al. 1994 Phase I and pharmacokinetic studies of topotecan administered as a 72 or 120 h continuous infusion. Anticancer Drugs 5:394–402.

    Google Scholar 

  45. Hochster H, Liebes L, Speyer J, 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 12:553–539.

    Google Scholar 

  46. Hochster H, Hibrahim J, Liebes L, O’Dwyer P, Benson A. 1997 Phase II study of 21-day topotecan continuous infusion for metastatic colorectal cancer (ECOG study 4293). Proc Am Soc Clin Oncol 16:1032.

    Google Scholar 

  47. Frangoul H, Ames MM, Mosher RB, et al. 1999 Phase I study of topotecan administered as a 21-day continous infusion in children with recurrent solid tumors: a report from the Children’s Cancer Group. Clin Cancer Res 5:3956–3962.

    Google Scholar 

  48. von Pawel J, Gatzemeier U, Pujol JL, et al. 2001 Phase II comparator study of oral versus intravenous topotecan in patients with chemosensitive small-cell lung cancer. J Clin Oncol 19:1743–1749.

    Google Scholar 

  49. Clarke-Pearson DL, Van Le L, Iveson T, et al. 2001 Oral topotecan as single-agent second-line chemotherapy in patients with advanced ovarian cancer. J Clin Oncol 19:3967–3975.

    Google Scholar 

  50. Gore M, Oza A, Rustin G, et al. 2002 A randomised trial of oral versus intravenous topotecan in patients with relapsed epithelial ovarian cancer. Eur J Cancer 38:57–63.

    Google Scholar 

  51. Gerrits CJ, Burris H, Schellens JH, et al. 1998 Five days of oral topotecan (Hycamtin), a phase I and pharmacological study in adult patients with solid tumours. Eur J Cancer 34:1030–1035.

    Google Scholar 

  52. Gerrits CJ, Burris H, Schellens JH, et al. 1998 Oral topotecan given once or twice daily for ten days: a phase I pharmacology study in adult patients with solid tumors. Clin Cancer Res 4:1153–1158.

    Google Scholar 

  53. Creemers GJ, Gerrits CJ, Eckardt JR, et al. 1997 Phase I and pharmacologic study of oral topotecan administered twice daily for 21 days to adult patients with solid tumors. J Clin Oncol 15:1087–1093.

    Google Scholar 

  54. Hofstra LS, Bos AM, de Vries EG, et al. 2001 A phase I and pharmacokinetic study of intraperitoneal topotecan. Br J Cancer 85:1627–1633.

    Google Scholar 

  55. Plaxe SC, Christen RD, O’Quigley J, et al. 1998 Phase I and pharmacokinetic study of intraperitoneal topotecan. Invest New Drugs 16:147–153.

    Google Scholar 

  56. Burke TG, Gao X. 1994 Stabilization of topotecan in low pH liposomes composed of distearoylphosphatidylcholine. J Pharm Sci 83:967–969.

    Google Scholar 

  57. Subramanian D, Muller MT. 1995 Liposomal encapsulation increases the activity of the topoisomerase I inhibitor topotecan. Oncol Res 7:461–469.

    Google Scholar 

  58. Tardi P, Choice E, Masin D, Redelmeier T, Bally M, Madden TD. 2000 Liposomal encapsulation of topotecan enhances anticancer efficacy in murine and human xenograft models. Cancer Res 60:3389–3393.

    Google Scholar 

  59. Verschraegen CF, Jaeckle K, Giovanella B, Knight V, Gilbert BE. 2000 Alternative administration of camptothecin analogues. Ann NY Acad Sci 922:237–426.

    Google Scholar 

  60. Blaney SM, Cole DE, Godwin K, Sung C, Poplack DG, Balis FM. 1995 Intrathecal administration of topotecan in nonhuman primates. Cancer Chemother Pharmacol 36:121–124.

    Google Scholar 

  61. Dowlati A, Levitan N, Gordon NH, et al. 2001 Phase II and pharmacokinetic/pharmacodynamic trial of sequential topoisomerase I and II inhibition with topotecan and etoposide in advanced non-small-cell lung cancer. Cancer Chemother Pharmacol 47:141–148.

    Google Scholar 

  62. von Pawel J, Schiller JH, Shepherd FA, et al. 1999 Topotecan versus cyclophosphamide, doxorubicin, and vincristine for the treatment of recurrent small-cell lung cancer. J Clin Oncol 17:658–667.

    Google Scholar 

  63. Grochow L, Slichenmyer W, Rowinsky E, Donehower R, Forastier A, Chen T-L. 1994 Phase I clinical and pharmacologic study of topotecan in patients with hepatic or renal dysfunction. Ann Oncol 5(Suppl.):191.

    Google Scholar 

  64. McGuire WP, Hoskins WJ, Brady MF, et al. 1995 Assessment of dose-intensive therapy in suboptimally debulked ovarian cancer: a Gynecologic Oncology Group study. J Clin Oncol 13:1589–1599.

    Google Scholar 

  65. Schiller JH. 2001 Current standards of care in small-cell and non-small-cell lung cancer. Oncology 61(Suppl. 1):3–13.

    Google Scholar 

  66. Saltz L, Janik JE. 1997 Topotecan and the treatment of recurrent ovarian cancer: is there a role for granulocyte colony-stimulating factor? Semin Oncol 24(Suppl. 5):S5-26–S5-30.

    Google Scholar 

  67. ten Bokkel Huinink W, Gore M, Carmichael J, et al. 1997 Topotecan versus paclitaxel for the treatment of recurrent epithelial ovarian cancer. J Clin Oncol 15:2183–2193.

    Google Scholar 

  68. Creemers GJ, Bolis G, Gore M, et al. 1996 Topotecan, an active drug in the second-line treatment of epithelial ovarian cancer: results of a large European phase II study. J Clin Oncol 14:3056–3061.

    Google Scholar 

  69. Beran M, Kantarjian H, O’Brien S, et al. 1996 Topotecan, a topoisomerase I inhibitor, is active in the treatment of myelodysplastic syndrome and chronic myelomonocytic leukemia. Blood 88:2473–2479.

    Google Scholar 

  70. von Pawel J, Depierre A, Hans K, et al. 1997 Topotecan (Hycamptin) in small cell lung cancer (SCLC) after failure of first line therapy: multicentre phase II study. Eur J Cancer 33(Suppl. 8):229.

    Google Scholar 

  71. Hochster H, Speyer J, Wadler S, et al. 1996 Phase II study of topotecan (TPT) 21-day infusion in platinum-treated ovarian cancer: a highly active regimen (A NYGOG study). Proc Am Soc Clin Oncol 15:285.

    Google Scholar 

  72. 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 18:1062–1067.

    Google Scholar 

  73. Zamboni WC, Gajjar AJ, Heideman RL, et al. 1998 Phenytoin alters the disposition of topotecan and N-desmethyl topotecan in a patient with medulloblastoma. Clin Cancer Res 4:783–789.

    Google Scholar 

  74. Stewart CF, Baker SD, Heideman RL, Jones D, Crom WR, Pratt CB. 1994 Clinical pharmacodynamics of continuous infusion topotecan in children: systemic exposure predicts hematologic toxicity. J Clin Oncol 12: 1946–1954.

    Google Scholar 

  75. Zamboni WC, Houghton PJ, Johnson RK, et al. 1998 Probenecid alters topotecan systemic and renal disposition by inhibiting renal tubular secretion. J Pharmacol Exp Ther 284:89–94.

    Google Scholar 

  76. Woessner RD, Eng WK, Hofmann GA, et al. 1992 Camptothecin hyper-resistant P388 cells: drug-dependent reduction in topoisomerase I content. Oncol Res 4:481–488.

    Google Scholar 

  77. Yang CH, Schneider E, Kuo ML, Volk EL, Rocchi E, Chen YC. 2000 BCRP/MXR/ABCP expression in topotecan-resistant human breast carcinoma cells. Biochem Pharmacol 60:831–837.

    Google Scholar 

  78. Fujimori A, Harker WG, Kohlhagen G, Hoki Y, Pommier Y. 1995 Mutation at the catalytic site of topoisomerase I in CEM/C2, a human leukemia cell line resistant to camptothecin. Cancer Res 55:1339–1346.

    Google Scholar 

  79. Sorensen M, Sehested M, Jensen PB. 1995 Characterisation of a human small-cell lung cancer cell line resistant to the DNA topoisomerase I-directed drug topotecan. Br J Cancer 72:399–404.

    Google Scholar 

  80. Danks MK, Garrett KE, Marion RC, Whipple DO. 1996 Subcellular redistribution of DNA topoisomerase I in anaplastic astrocytoma cells treated with topotecan. Cancer Res 56:1664–1673.

    Google Scholar 

  81. Buckwalter CA, Lin AH, Tanizawa A, Pommier YG, Cheng YC, Kaufmann SH. 1996 RNA synthesis inhibitors alter the subnuclear distribution of DNA topoisomerase I. Cancer Res 56:1674–1681.

    Google Scholar 

  82. Mo YY, Yu Y, Shen Z, Beck WT. 2002 Nucleolar delocalization of human topoisomerase I in response to topotecan correlates with sumoylation of the protein. J Biol Chem 277:2958–2964.

    Google Scholar 

  83. Chang AY, Garrow G, Boros L, Asbury R, Pandya K, Keng P. 1995 Clinical and laboratory studies of topotecan in breast cancer. Proc Am Soc Clin Oncol 13:118.

    Google Scholar 

  84. Ejendal KF, Hrycyna CA. 2002 Multidrug resistance and cancer: the role of the human ABC transporter ABCG2. Curr Protein Pept Sci 3:503–511.

    Google Scholar 

  85. Bates SE, Robey R, Miyake K, Rao K, Ross DD, Litman T. 2001 The role of half-transporters in multidrug resistance. J Bioenerg Biomembr 33:503–511.

    Google Scholar 

  86. Maliepaard M, Nooter K, Ma J, et al. 1996 Relationship between P-glycoprotein, multidrug resistance-associated protein, and cellular accumulation of topoisomerase I inhibitors. Proc am Assoc Cancer Res 37:313.

    Google Scholar 

  87. Chen AY, Yu C, Potmesil M, Wall ME, Wani MC, Liu LF. 1991 Camptothecin overcomes MDR1-mediated resistance in human KB carcinoma cells. Cancer Res 51:6039–6044.

    Google Scholar 

  88. Hoki Y, Fujimori A, Pommier Y. 1997 Differential cytotoxicity of clinically important camptothecin derivatives in P-glycoprotein-overexpressing cell lines. Cancer Chemother Pharmacol 40:433–438.

    Google Scholar 

  89. Hendricks CB, Rowinsky EK, Grochow LB, Donehower RC, Kaufmann SH. 1992 Effect of P-glycoprotein expression on the accumulation and cytotoxicity of topotecan (SK&F 104864), a new camptothecin analogue. Cancer Res 52: 2268–2278.

    Google Scholar 

  90. Mattern MR, Hofmann GA, Polsky RM, Funk LR, McCabe FL, Johnson RK. 1993 In vitro and in vivo effects of clinically important camptothecin analogues on multidrug-resistant cells. Oncol Res 5:467–474.

    Google Scholar 

  91. Hoskins P, Eisenhauer E, Beare S, et al. 1998 Randomized phase II study of two schedules of topotecan in previously treated patients with ovarian cancer: a National Cancer Institute of Canada Clinical Trials Group study. J Clin Oncol 16:2233–2337.

    Google Scholar 

  92. Kudelka AP, Tresukosol D, Edwards CL, et al. 1996 Phase II study of intravenous topotecan as a 5-day infusion for refractory epithelial ovarian carcinoma. J Clin Oncol 14:1552–1557.

    Google Scholar 

  93. Swisher EM, Mutch DG, Rader JS, Elbendary A, Herzog TJ. 1997 Topotecan in platinum-and paclitaxel-resistant ovarian cancer. Gynecol Oncol 66:480–486.

    Google Scholar 

  94. Bookman MA, Malmstrom H, Bolis G, et al. 1998 Topotecan for the treatment of advanced epithelial ovarian cancer: an open-label phase II study in patients treated after prior chemotherapy that contained cisplatin or carboplatin and paclitaxel. J Clin Oncol 16:3345–3352.

    Google Scholar 

  95. Gordon A, Carmichael J, Malfetano J, et al. 1998 Final analysis of a phase III, randomized study of topotecan (T) vs paclitaxel (P) in advanced epithelial ovarian carcinoma (OC): International Topotecan Study Group [abstract]. Proc Am Soc Clin Oncol 17:abstr 1374.

    Google Scholar 

  96. Gore M, ten Bokkel Huinink W, Carmichael J, et al. 2001 Clinical evidence for topotecan-paclitaxel non-cross-resistance in ovarian cancer. J Clin Oncol 19:1893–1900.

    Google Scholar 

  97. 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: 3312–3322.

    Google Scholar 

  98. Brown JV 3rd, Peters WA 3rd, Rettenmaier MA, et al. 2003 Three-consecutive-day topotecan is an active regimen for recurrent epithelial ovarian cancer. Gynecol Oncol 88:136–140.

    Google Scholar 

  99. Gore M, Rustin G, Schuller J, et al. 2001 Topotecan given as a 21-day infusion in the treatment of advanced ovarian cancer. Br J Cancer 84:1043–1046.

    Google Scholar 

  100. Ardizzoni A, Hansen H, Dombernowsky 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. The European Organization for Research and Treatment of Cancer Early Clinical Studies Group and New Drug Development Office, and the Lung Cancer Cooperative Group. J Clin Oncol 15:2090–2096.

    Google Scholar 

  101. Eckhardt J, Gralla R, Palmer MC, et al. 1996 Topotecan as a second-line therapy in patients with small-cell-lung cancer: A phase II study [abstract]. Ann Oncol 7:107.

    Google Scholar 

  102. Perez-Soler R, Glisson BS, Lee JS, et al. 1996 Treatment of patients with small-cell lung cancer refractory to etoposide and cisplatin with the topoisomerase I poison topotecan. J Clin Oncol 14:2785–2790.

    Google Scholar 

  103. Schiller JH, Kim K, Hutson P, 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 14:2345–2352.

    Google Scholar 

  104. Schiller JH, Adak S, Cella D, DeVore RF 3rd, Johnson DH. 2001 Topotecan versus observation after cisplatin plus etoposide in e xtensive-stage small-cell lung cancer: E7593—a phase III trial of the Eastern Cooperative Oncology Group. J Clin Oncol 19:2114–2122.

    Google Scholar 

  105. Kraut EH, Staubus A, Mayernick D, King G, Balcerzak SP. 1995 Phase II trial of topotecan in metastatic malignant melanoma. Proc Am Assoc Cancer Res 36:1420.

    Google Scholar 

  106. Beran M, Estey E, O’Brien SM, et al. 1998 Results of topotecan single-agent therapy in patients with myelodysplastic syndromes and chronic myelomonocytic leukemia. Leuk Lymphoma 31:521–531.

    Google Scholar 

  107. Blaney SM, Needle MN, Gillespie A, et al. 1998 Phase II trial of topotecan administered as 72-hour continuous infusion in children with refractory solid tumors: a collaborative Pediatric Branch, National Cancer Institute, and Children’s Cancer Group Study. Clin Cancer Res 4:357–360.

    Google Scholar 

  108. Nitschke R, Parkhurst J, Sullivan J, Harris MB, Bernstein M, Pratt C. 1998 Topotecan in pediatric patients with recurrent and progressive solid tumors: a Pediatric Oncology Group phase II study. J Pediatr Hematol Oncol 20:315–318.

    Google Scholar 

  109. Kretschmar C, Kletzel M, Murray K, et al. 1995 Upfront phase II therapy with Taxol (Txl) and topotecan in untreated children (>365 days) with disseminated (INSS stage 4) neuroblastoma. Med Pediat Oncol 25:243.

    Google Scholar 

  110. Pinkerton CR, Blanc Vincent MP, Bergeron C, Fervers B, Philip T. 2000 Induction chemotherapy in metastatic neuroblastoma—does dose influence response? A critical review of published data standards, options and recommendations (SOR) project of the National Federation of French Cancer Centres (FNCLCC). Eur J Cancer 36: 1808–1815.

    Google Scholar 

  111. Blaney SM, Phillips PC, Packer RJ, et al. 1996 Phase II evaluation of topotecan for pediatric central nervous system tumors. Cancer 78:527–531.

    Google Scholar 

  112. Kadota RP, Stewart CF, Horn M, et al. 1999 Topotecan for the treatment of recurrent or progressive central nervous system tumors—a Pediatric Oncology Group phase II study. J Neurooncol 43:43–47.

    Google Scholar 

  113. Lynch TJ, Kalish L, Strauss G, et al. 1994 Phase II study of topotecan in metastatic non-small-cell lung cancer. J Clin Oncol 12:347–352.

    Google Scholar 

  114. Perez-Soler R, Fossella FV, Glisson BS, et al. 1996 Phase II study of topotecan in patients with advanced non-small-cell lung cancer previously untreated with chemotherapy. J Clin Oncol 14:503–513.

    Google Scholar 

  115. Kindler HL, Kris MG, Smith IE, Slevin ML, Krebs JB. 1997 Continuous infusion topotecan as first-line therapy in patients with advanced non-small cell lung cancer (NSCLC): a Phase II study. Proc Am Soc Clin Oncol 16: 472.

    Google Scholar 

  116. Weitz JJ, Marschke RF, Sloan JA, et al. 2000 A randomized phase II trial of two schedules of topotecan for the treatment of advanced stage non-small cell lung cancer. Lung Cancer 28:157–162.

    Google Scholar 

  117. Perez-Soler R, Khuri F, Pisters KM, et al. 1997 Phase II study of topotecan in patients with squamous carcinoma of the lung previously untreated with chemotherapy. Proc Am Soc Clin Oncol 16:450.

    Google Scholar 

  118. Mainwaring PN, Nicolson MC, Hickish T, et al. 1997 Continuous infusional topotecan in advanced breast and non-small-cell lung cancer: no evidence of increased efficacy. Br J Cancer 76:1636–1639.

    Google Scholar 

  119. White SC, Cheeseman S, Thatcher N, et al. 2000 Phase II study of oral topotecan in advanced non-small cell lung cancer. Clin Cancer Res 6:868–873.

    Google Scholar 

  120. Creemers GJ, Wanders J, Gamucci T, et al. 1995 Topotecan in colorectal cancer: a phase II study of the EORTC early clinical trials group. Ann Oncol 6:844–846.

    Google Scholar 

  121. Macdonald JS, Benedetti JK, Modiano M, Alberts DS. 1997 Phase II evaluation of topotecan in patients with advanced colorectal cancer. A Southwest Oncology Group trial (SWOG 9241). Invest New Drugs 15:357–359.

    Google Scholar 

  122. Saltz LB, Schwartz GK, Ilson DH, Quan V, Kelsen DP. 1997 A phase II study of topotecan administered five times daily in patients with advanced gastric cancer. Am J Clin Oncol 20:621–625.

    Google Scholar 

  123. Benedetti JK, Burris HA, 3rd, Balcerzak SP, Macdonald JS. 1997 Phase II trial of topotecan in advanced gastric cancer: a Southwest Oncology Group study. Invest New Drugs 15:261–264.

    Google Scholar 

  124. Scher RM, Kosierowski R, Lusch C, et al. 1996 Phase II trial of topotecan in advanced or metastatic adenocarcinoma of the pancreas. Invest New Drugs 13:347–354.

    Google Scholar 

  125. O’Reilly S, Donehower RC, Rowinsky EK, Ord S, Grochow LB. 1996 A phase II trial of topotecan in patients with previously untreated pancreatic cancer. Anticancer Drugs 7:410–414.

    Google Scholar 

  126. Stevenson JP, Scher RM, Kosierowski R, 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 34:1358–1362.

    Google Scholar 

  127. Asbury RF, Lipsitz S, Graham D, Falkson CI, Baez L, Benson AB 3rd. 2000 Treatment of squamous cell esophageal cancer with topotecan: an Eastern Cooperative Oncology Group Study (E2293). Am J Clin Oncol 23: 45–46.

    Google Scholar 

  128. Macdonald JS, Jacobson JL, Ketchel SJ, et al. 2000 A phase II trial of topotecan in esophageal carcinoma: a Southwest Oncology Group study (SWOG 9339). Invest New Drugs 18:199–202.

    Google Scholar 

  129. Friedman HS, Kerby T, Fields S, et al. 1999 Topotecan treatment of adults with primary malignant glioma. The Brain Tumor Center at Duke. Cancer 85:1160–1165.

    Google Scholar 

  130. Macdonald D, Cairncross G, Stewart D, et al. 1996 Phase II study of topotecan in patients with recurrent malignant glioma. National Clinical Institute of Canada Clinical Trials Group. Ann Oncol 7:205–207.

    Google Scholar 

  131. Burch PA, Bernath AM, Cascino TL, et al. 2000 A North Central Cancer Treatment Group phase II trial of topotecan in relapsed gliomas. Invest New Drugs 18:275–280.

    Google Scholar 

  132. Rajkumar SV, Reid JM, Novotny PJ, et al. 2000 A randomized phase II and pharmacokinetic study of dacarbazine in patients with recurrent glioma. J Neurooncol 49:255–261.

    Google Scholar 

  133. Avgeropoulos NG, Batchelor TT. 1999 New treatment strategies for malignant gliomas. Oncologist 4: 209–224.

    Google Scholar 

  134. Murphy BA, Leong T, Burkey B, Langer C, Forastiere A. 2001 Lack of efficacy of topotecan in the treatment of metastatic or recurrent squamous carcinoma of the head and neck: an Eastern Cooperative Oncology Group Trial (E3393). Am J Clin Oncol 24:64–66.

    Google Scholar 

  135. Smith RE, Lew D, Rodriguez GI, Taylor SA, Schuller D, Ensley JF. 1996 Evaluation of topotecan in patients with recurrent for metastatic squamous cell carcinoma of the head and neck. A phase II Southwest Oncology Group study. Invest New Drugs 14:403–407.

    Google Scholar 

  136. Robert F, Soong SJ, Wheeler RH. 1997 A phase II study of topotecan in patients with recurrent head and neck cancer. Identification of an active new agent. Am J Clin Oncol 20:298–302.

    Google Scholar 

  137. Goldschmidt E, Bonneterre J, Fumoleau P, Oberling F, Cupissol D, Misset JL. 1997 A phase II study of topotecan on a daily x 5 schedule as second-line single agent therapy in patients with advanced breast cancer. Proc Am Soc Clin Oncol 16:598.

    Google Scholar 

  138. Levine EG, Cirrincione CT, Szatrowski TP, Canellos G, Norton L, Henderson IC. 1999 Phase II trial of topotecan in advanced breast cancer: a Cancer and Leukemia Group B study. Am J Clin Oncol 22:218–222.

    Google Scholar 

  139. Spaeth D, Bonneterre J, Marty M, Khayat D, Facchini T, Conroy T. 1997 Phase II studies of two trial regimens of topotecan as second-line single agent therapy in advanced breast cancer. Proc Am Soc Clin Oncol 16: 675.

    Google Scholar 

  140. Oberhoff C, Kieback DG, Wurstlein R, et al. 2001 Topotecan chemotherapy in patients with breast cancer and brain metastases: results of a pilot study. Onkologie 24:256–260.

    Google Scholar 

  141. Holloway RW. 2003 Treatment options for endometrial cancer: experience with topotecan. Gynecol Oncol 90:S28–S33.

    Google Scholar 

  142. 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 21:2110–2114.

    Google Scholar 

  143. Miller DS, Blessing JA, Lentz SS, Waggoner SE. 2002 A phase II trial of topotecan in patients with advanced, persistent, or recurrent endometrial carcinoma: a gynecologic oncology group study. Gynecol Oncol 87: 247–251.

    Google Scholar 

  144. Noda K, Sasaki H, Yamamoto K, et al. 1996 Phase II trial of topotecan for cervical cancer of the uterus. Proc Am Soc Clin Oncol 15:754.

    Google Scholar 

  145. 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 77:446–449.

    Google Scholar 

  146. Abu-Rustum NR, Lee S, Massad LS. 2000 Topotecan for recurrent cervical cancer after platinum-based therapy. Int J Gynecol Cancer 10:285–288.

    Google Scholar 

  147. Muderspach LI, Blessing JA, Levenback C, Moore JL Jr. 2001 A phase II study of topotecan in patients with squamous cell carcinoma of the cervix: a Gynecologic Oncology Group study. Gynecol Oncol 81:213–215.

    Google Scholar 

  148. Hudes GR, Kosierowski R, Greenberg R, et al. 1995 Phase II study of topotecan in metastatic hormone-refractory prostate cancer. Invest New Drugs. 13:235–240.

    Google Scholar 

  149. Klein CE, Tangen CM, Braun TJ, et al. 2002 SWOG-9510: evaluation of topotecan in hormone refractory prostate cancer: a Southwest Oncology Group study. Prostate 52:264–268.

    Google Scholar 

  150. Janik JE, Miller LL, Korn EL, et al. 2001 A prospective randomized phase II trial of GM-CSF priming to prevent topotecan-induced neutropenia in chemotherapy-naive patients with malignant melanoma or renal cell carcinoma. Blood 97:1942–1946.

    Google Scholar 

  151. Wall JG, Benedetti JK, O’Rourke MA, Natale RB, Macdonald JS. 1997 Phase II trial to topotecan in hepatocellular carcinoma: a Southwest Oncology Group study. Invest New Drugs 15:257–260.

    Google Scholar 

  152. Chou TC, Motzer RJ, Tong Y, Bosl GJ. 1994 Computerized quantitation of synergism and antagonism of taxol, topotecan, and cisplatin against human teratocarcinoma cell growth: a rational approach to clinical protocol design. J Natl Cancer Inst 86:1517–1524.

    Google Scholar 

  153. Cheng MF, Chatterjee S, Berger NA. 1994 Schedule-dependent cytotoxicity of topotecan alone and in combination chemotherapy regimens. Oncol Res 6:269–279.

    Google Scholar 

  154. Kaufmann SH, Gore SD, Letendre L, et al. 1996 Factors affecting topotecan sensitivity in human leukemia samples. Ann NY Acad Sci 803:128–142.

    Google Scholar 

  155. Kaufmann SH, Peereboom D, Buckwalter CA, et al. 1996 Cytotoxic effects of topotecan combined with various anticancer agents in human cancer cell lines. J Natl Cancer Inst 88:734–741.

    Google Scholar 

  156. Ma J, Maliepaard M, Nooter K, et al. 1998 Synergistic cytotoxicity of cisplatin and topotecan or SN-38 in a panel of eight solid-tumor cell lines. Cancer Chemother Pharmacol 41:307–316.

    Google Scholar 

  157. Romanelli S, Perego P, Pratesi G, Carenini N, Tortoreto M, Zunino F. 1998 In vitro and in vivo interaction between cisplatin and topotecan in ovarian carcinoma systems. Cancer Chemother Pharmacol 41: 385–390.

    Google Scholar 

  158. Kim JH, Kim SH, Kolozsvary A, Khil MS. 1992Potentiation 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 22:515–518.

    Google Scholar 

  159. Bonner JA, Kozelsky TF. 1996 The significance of the sequence of administration of topotecan and etoposide. Cancer Chemother Pharmacol 39:109–112.

    Google Scholar 

  160. Whitacre CM, Zborowska E, Gordon NH, Mackay W, Berger NA. 1997 Topotecan increases topoisomerase IIalpha levels and sensitivity to treatment with etoposide in schedule-dependent process. Cancer Res 57:1425–1428.

    Google Scholar 

  161. Rowinsky EK, Kaufmann SH, Baker SD, et al. 1996 Sequences of topotecan and cisplatin: phase I, pharmacologic, and in vitro studies to examine sequence dependence. J Clin Oncol 14:3074–3084.

    Google Scholar 

  162. Bolis G, Scarfone G, Villa A, Parazzini F. 2001 Phase II trial of topotecan, carboplatin, and paclitaxel as front-line therapy in suboptimal advanced epithelial ovarian cancer. Gynecol Oncol 81:331–333.

    Google Scholar 

  163. du Bois A, Luck HJ, Meier W, et al. 1997 Carboplatin/paclitaxel versus cisplatin/paclitaxel as first-line chemotherapy in advanced ovarian cancer: an interim analysis of a randomized phase III trial of the Arbeitsgemeinschaft Gynakologische Onkologie Ovarian Cancer Study Group. Semin Oncol 24(Suppl. 15): S15-44–S15-52.

    Google Scholar 

  164. Neijt JP, Engelholm SA, Tuxen MK, et al. 2000 Exploratory phase III study of paclitaxel and cisplatin versus paclitaxel and carboplatin in advanced ovarian cancer. J Clin Oncol 18:3084–3092.

    Google Scholar 

  165. Pignata S, Deplacido S, Scambia G, et al. 2003 Topotecan vs nihil after response to carboplatin and paclitaxel in advanced ovarian cancer. Early results of the MITO-1 (Multicenter Italian Trials in Ovarian Cancer) study [abstract]. Proc Am Soc Clin Oncol 22:1791.

    Google Scholar 

  166. Pfisterer J, Lortholary A, Kimmig R, et al. 2003 Paclitaxel/carboplatin (TC) vs. paclitaxel/carboplatin followed by topotecan (TC-Top) in first-line treatment of ovarian cancer FIGO stages IIb-IV. Interim results of a gynecologic cancer inter-group phase III trial of the AGO Ovarian Cancer Study Group and GINECO [abstract]. Proc Am Soc Clin Oncol 22:1793.

    Google Scholar 

  167. McGuire WP, Hoskins WJ, Brady MF, et al. 1996 Cyclophosphamide and cisplatin compared with paclitaxel and cisplatin in patients with stage III and stage IV ovarian cancer. N Engl J Med 334:1–6.

    Google Scholar 

  168. Greggi S, Salerno MG, D’Agostino G, et al. 2001 Topotecan and gemcitabine in platinum/paclitaxel-resistant ovarian cancer. Oncology 60:19–23.

    Google Scholar 

  169. Sehouli J, Stengel D, Oskay G, et al. 2002 A phase II study of topotecan plus gemcitabine in the treatment of patients with relapsed ovarian cancer after failure of first-line chemotherapy. Ann Oncol 13:1749–1755.

    Google Scholar 

  170. Penson RT, Supko JG, Seiden MV, et al. 2001 A Phase I-II study of 96-hour infusional topotecan and paclitaxel for patients with recurrent Mullerian tumors. Cancer 92:1156–1167.

    Google Scholar 

  171. Hanjani P, Nolte S, Shahin MS. 2002 Phase II evaluation of 3-day topotecan with cyclophosphamide in the treatment of recurrent ovarian cancer. Gynecol Oncol 85:278–284.

    Google Scholar 

  172. Bookman MA. 2002 Developmental chemotherapy in advanced ovarian cancer: incorporation of newer cytotoxic agents in a phase III randomized trial of the Gynecologic Oncology Group (GOG-0182). Semin Oncol 29:20–31.

    Google Scholar 

  173. Copeland LJ, Bookman M, Trimble E. 2003 Clinical trials of newer regimens for treating ovarian cancer: the rationale for Gynecologic Oncology Group Protocol GOG 182-ICON5. Gynecol Oncol 90:S1–S7.

    Google Scholar 

  174. Frasci G, Nicolella G, Comella P, et al. 2001 A weekly regimen of cisplatin, paclitaxel and topotecan with granulocyte-colony stimulating factor support for patients with extensive disease small cell lung cancer: a phase II study. Br J Cancer 84:1166–1171.

    Google Scholar 

  175. Hainsworth JD, Morrissey LH, Scullin DC, Jr., et al. 2002 Paclitaxel, carboplatin, and topotecan in the treatment of patients with small cell lung cancer: a phase II trial of the Minnie Pearl Cancer Research Network. Cancer 94:2426–2433.

    Google Scholar 

  176. Jacobs S, Jett J, Belani C, et al. 1999 Topotecan and paclitaxel, an active couplet in untreated extensive disease in small cell lung cancer. Proc Am Soc Clin Oncol 18:470a.

    Google Scholar 

  177. Felip E, Rosell R, Domine M, et al. 2003 Sequential dose-dense paclitaxel followed by topotecan in untreated extensive-stage small-cell lung cancer: a Spanish Lung Cancer Group phase II study. Ann Oncol 14: 1549–1554.

    Google Scholar 

  178. Kelly K. 2000 New chemotherapy agents for small cell lung cancer. Chest 117(Suppl. 1): 156S–1562S.

    Google Scholar 

  179. Ardizzoni A, Manegold C, Debruyne C, et al. 2003 European organization for research and treatment of cancer (EORTC) 08957 phase II study of topotecan in combination with cisplatin as second-line treatment of refractory and sensitive small cell lung cancer. Clin Cancer Res 9:143–150.

    Google Scholar 

  180. Hammond LA, Eckardt JR, Ganapathi R, et al. 1998 A phase I and translational study of sequential administration of the topoisomerase I and II inhibitors topotecan and etoposide. Clin Cancer Res 4: 1459–1467.

    Google Scholar 

  181. Joppert MG, Garfield DH, Gregurich MA, et al. 2003 A phase II multicenter study of combined topotecan and gemcitabine as first line chemotherapy for advanced non-small cell lung cancer. Lung Cancer 39:215–219.

    Google Scholar 

  182. Rinaldi D, Lormand N, Brierre J, et al. 2001 A phase I-II trial of topotecan and gemcitabine in patients with previously treated, advanced non-small cell lung cancer (LOA-3). Cancer Invest 19:467–474.

    Google Scholar 

  183. Rinaldi DA, Lormand NA, Brierre JE, et al. 2002 A Phase II trial of topotecan and gemcitabine in patients with previously treated, advanced nonsmall cell lung carcinoma. Cancer 95(6):1274–1278.

    Google Scholar 

  184. Stupp R, Bodmer A, Duvoisin B, et al. 2001 Is cisplatin required for the treatment of non-small-cell lung cancer? Experience and preliminary results of a phase I/II trial with topotecan and vinorelbine. Oncology 61(Suppl. 1):35–41.

    Google Scholar 

  185. Pujol JL, von Pawel J, Tumolo S, et al. 2001 Preliminary results of combined therapy with topotecan and carboplatin in advanced non-small-cell lung cancer. Oncology 61(Suppl. 1):47–54.

    Google Scholar 

  186. Beran M, Estey E, O’Brien S, et al. 1999 Topotecan and cytarabine is an active combination regimen in myelodysplastic syndromes and chronic myelomonocytic leukemia. J Clin Oncol 17:2819–2830.

    Google Scholar 

  187. Kancherla RR, Nair JS, Ahmed T, et al. 2001 Evaluation of topotecan and etoposide for non-Hodgkin lymphoma: correlation of topoisomerase-DNA complex formation with clinical response. Cancer 91:463–471.

    Google Scholar 

  188. Younes A, Preti HA, Hagemeister FB, et al. 2001 Paclitaxel plus topotecan treatment for patients with relapsed or refractory aggressive non-Hodgkin’s lymphoma. Ann Oncol 12:923–927.

    Google Scholar 

  189. Cortes J, Estey E, Beran M, et al. 2000 Cyclophosphamide, ara-C and topotecan (CAT) for patients with refractory or relapsed acute leukemia. Leuk Lymph 36:479–484.

    Google Scholar 

  190. Lee ST, Jang JH, Suh HC, Hahn JS, Ko YW, Min YH. 2001 Idarubicin, cytarabine, and topotecan in patients with refractory or relapsed acute myelogenous leukemia and high-risk myelodysplastic syndrome. Am J Hematol 68: 237–245.

    Google Scholar 

  191. Vey N, Kantarjian H, Beran M, et al. 1999 Combination of topotecan with cytarabine or etoposide in patients with refractory or relapsed acute myeloid leukemia: results of a randomized phase I/II study. Invest New Drugs 17: 89–95.

    Google Scholar 

  192. Crump M, Couban S, Meyer R, 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 Lymph 43158:1581–1587.

    Google Scholar 

  193. Mainwaring MG, Rimsza LM, Chen SF, et al. 2002 Treatment of refractory acute leukemia with timed sequential chemotherapy using topotecan followed by etoposide + mitoxantrone (T-EM) and correlation with topoisomerase II levels. Leuk Lymph 43:989–999.

    Google Scholar 

  194. Kushner BH, Cheung NK, Kramer K, Dunkel IJ, Calleja E, Boulad F. 2001 Topotecan combined with myeloablative doses of thiotepa and carboplatin for neuroblastoma, brain tumors, and other poor-risk solid tumors in children and young adults. Bone Marrow Transplant 28:551–556.

    Google Scholar 

  195. Donato ML, Gershenson DM, Wharton JT, et al. 2001 High-dose topotecan, melphalan, and cyclophosphamide (TMC) with stem cell support: a new regimen for the treatment of advanced ovarian cancer. Gynecol Oncol 82: 420–426.

    Google Scholar 

  196. Prince HM, Rischin D, Quinn M, et al. 2001 Repetitive high-dose topotecan, carboplatin, and paclitaxel with peripheral blood progenitor cell support in previously untreated ovarian cancer: results of a Phase I study. Gynecol Oncol 81:216–224.

    Google Scholar 

  197. Colombo NobotIc. 2000 Randomised trial of paclitaxel (PTX) and carboplatin (CBDCA) versus a control arm of carboplatin or CAP (cyclophosphamide, doxorubicin, & cisplatin): The Third International Collaborative Ovarian Neoplasm Study (ICON3). Proc Am Soc Clin Oncol 19:1500.

    Google Scholar 

  198. Muggia FM, Braly PS, Brady MF, et al. 2000 Phase III randomized study of cisplatin versus paclitaxel versus cisplatin and paclitaxel in patients with suboptimal stage III or IV ovarian cancer: a Gynecologic Oncology Group study. J Clin Oncol 18:106–115.

    Google Scholar 

  199. Eckardt JR. 2001 Feasibility of oral topotecan plus intravenous paclitaxel in advanced non-small-cell lung cancer. Oncology 61(Suppl. 1):30–34.

    Google Scholar 

  200. O’Leary JJ, Shapiro RL, Ren CJ, Chuang N, Cohen HW, Potmesil M. 1999 Antiangiogenic effects of camptothecin analogues 9-amino-20(S)-camptothecin, topotecan, and CPT-11 studied in the mouse cornea model. Clin Cancer Res 5:181–187.

    Google Scholar 

  201. Nakashio A, Fujita N, Tsuruo T. 2002 Topotecan inhibits VEGF-and bFGF-induced vascular endothelial cell migration via downregulation of the PI3K-Akt signaling pathway. Int J Cancer 98:36–41.

    Google Scholar 

  202. McCrudden KW, Yokoi A, Thosani A, et al. 2002 Topotecan is anti-angiogenic in experimental hepatoblastoma. J Pediatr Surg 37:857–861.

    Google Scholar 

  203. Soffer SZ, Kim E, Moore JT, et al. 2001 Novel use of an established agent: Topotecan is anti-angiogenic in experimental Wilms tumor. J Pediatr Surg 36:1781–1784.

    Google Scholar 

  204. Soffer SZ, Moore JT, Kim E, et al. 2001 Combination antiangiogenic therapy: increased efficacy in a murine model of Wilms tumor. J Pediatr Surg 36:1177–1181.

    Google Scholar 

  205. Ling YH, Donato NJ, Perez-Soler R. 2001 Sensitivity to topoisomerase I inhibitors and cisplatin is associated with epidermal growth factor receptor expression in human cervical squamous carcinoma ME180 sublines. Cancer Chemother Pharmacol 47:473–480.

    Google Scholar 

  206. Erlichman C, Boerner SA, Hallgren CG, et al. 2001 The HER tyrosine kinase inhibitor CI1033 enhances cytotoxicity of 7-ethyl-10-hydroxycamptothecin and topotecan by inhibiting breast cancer resistance protein-mediated drug efflux. Cancer Res 61:739–748.

    Google Scholar 

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  1. Department of Pharmacy Practice and Science, College of Pharmacy, University of Kentucky, Lexington, KY

    Aimee K. Bence PhD & Val R. Adams PharmD

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  1. Department of Pharmacy Practice and Science, College of Pharmacy, University of Kentucky, Lexington, KY

    Val R. Adams PharmD

  2. Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, KY

    Thomas G. Burke PhD

  3. Experimental Therapeutics Program, Lucille P. Markey Cancer Center, University of Kentucky Medical Center, University of Kentucky, Lexington, KY

    Thomas G. Burke PhD

  4. Tigen Pharmaceuticals Inc., Lexington, KY

    Thomas G. Burke PhD

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Bence, A.K., Adams, V.R. (2005). Clinical Experience With Topotecan. In: Adams, V.R., Burke, T.G. (eds) Camptothecins in Cancer Therapy. Cancer Drug Discovery and Development. Humana Press. https://doi.org/10.1385/1-59259-866-8:263

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