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 Topotecan

Topocecan hydrochloride is the hydrochloride salt of a semisynthetic derivative of camptothecin with antineoplastic activity. During the S phase of the cell cycle, topotecan selectively stabilizes topoisomerase I-DNA covalent complexes, inhibiting religation of topoisomerase I-mediated single-strand DNA breaks and producing potentially lethal double-strand DNA breaks when complexes are encountered by the DNA replication machinery. Camptothecin is a cytotoxic quinoline-based alkaloid extracted from the Asian tree Camptotheca acuminata. Check for active clinical trials or closed clinical trials using this agent. (NCI Thesaurus)

HYCAMTIN (topotecan hydrochloride) is a semi-synthetic derivative of camptothecin and is an anti-tumor drug with topoisomerase I-inhibitory activity. HYCAMTIN for Injection is supplied as a sterile lyophilized, buffered, light yellow to greenish powder available in single-dose vials. Each vial contains topotecan hydrochloride equivalent to 4 mg of topotecan as free base. The reconstituted solution ranges in color from yellow to yellow-green and is intended for administration by intravenous infusion. Inactive ingredients are mannitol, 48 mg, and tartaric acid, 20 mg. Hydrochloric acid and sodium hydroxide may be used to adjust the pH. The solution pH ranges from 2.5 to 3.5.

FDA approved for treating: ovarian cancer (FDA May 1996); cervical cancer (FDA June 2006); small cell lung cancer (SCLC) (FDA Oct 2007).

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21: Markman M. Chemotherapy: Topotecan or treosulfan--that is the question. Nat Rev Clin Oncol. 2009 Oct;6(10):559-60. PubMed PMID: 19786996.

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23: Bigioni M, Parlani M, Bressan A, Bellarosa D, Rivoltini L, Animati F, Crea A, Bugianesi R, Maggi CA, Manzini S, Binaschi M. Antitumor activity of delimotecan against human metastatic melanoma: pharmacokinetics and molecular determinants. Int J Cancer. 2009 Nov 15;125(10):2456-64. PubMed PMID: 19536774.

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30: Sehouli J, Oskay-Ozcelik G. Current role and future aspects of topotecan in relapsed ovarian cancer. Curr Med Res Opin. 2009 Mar;25(3):639-51. PubMed PMID: 19232038.

31: Bookman MA, Brady MF, McGuire WP, Harper PG, Alberts DS, Friedlander M, Colombo N, Fowler JM, Argenta PA, De Geest K, Mutch DG, Burger RA, Swart AM, Trimble EL, Accario-Winslow C, Roth LM. Evaluation of new platinum-based treatment regimens in advanced-stage ovarian cancer: a Phase III Trial of the Gynecologic Cancer Intergroup. J Clin Oncol. 2009 Mar 20;27(9):1419-25. Epub 2009 Feb 17. Erratum in: J Clin Oncol. 2009 May 1;27(13):2305. PubMed PMID: 19224846; PubMed Central PMCID: PMC2668552.

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37: Hollingshead MG. Antitumor efficacy testing in rodents. J Natl Cancer Inst. 2008 Nov 5;100(21):1500-10. Epub 2008 Oct 28. PubMed PMID: 18957675; PubMed Central PMCID: PMC2597219.

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40: Robati M, Holtz D, Dunton CJ. A review of topotecan in combination chemotherapy for advanced cervical cancer. Ther Clin Risk Manag. 2008 Feb;4(1):213-8. PubMed PMID: 18728710; PubMed Central PMCID: PMC2503656.

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47: Liew ST, Yang LX. Design, synthesis and development of novel camptothecin drugs. Curr Pharm Des. 2008;14(11):1078-97. Review. PubMed PMID: 18473856.

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49: Wang HK. Plant-derived anticancer agents currently in clinical use or in clinical trials. IDrugs. 1998 May;1(1):92-102. PubMed PMID: 18465513.

50: Peng LH, Chen XY, Wu TX. Topotecan for ovarian cancer. Cochrane Database Syst Rev. 2008 Apr 16;(2):CD005589. Review. PubMed PMID: 18425923.

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52: Moore DH. Chemotherapy for advanced, recurrent, and metastatic cervical cancer. J Natl Compr Canc Netw. 2008 Jan;6(1):53-7. Review. PubMed PMID: 18267059.

53: Park SH, Cho EK, Kim Y, Kyung SY, An CH, Lee SP, Park JW, Jeong SH, Lee JI, Choi SJ, Park J, Shin DB, Lee JH. Salvage treatment with topotecan in patients with irinotecan-refractory small cell lung cancer. Cancer Chemother Pharmacol. 2008 Nov;62(6):1009-14. Epub 2008 Feb 8. PubMed PMID: 18259751.

54: Weller M. [Chemotherapy for brain tumors in adult patients]. Nervenarzt. 2008 Feb;79(2):231-41. German. PubMed PMID: 18253773.

55: Panetta JC, Schaiquevich P, Santana VM, Stewart CF. Using pharmacokinetic and pharmacodynamic modeling and simulation to evaluate importance of schedule in topotecan therapy for pediatric neuroblastoma. Clin Cancer Res. 2008 Jan 1;14(1):318-25. PubMed PMID: 18172284.

56: Takagi K, Dexheimer TS, Redon C, Sordet O, Agama K, Lavielle G, Pierré A, Bates SE, Pommier Y. Novel E-ring camptothecin keto analogues (S38809 and S39625) are stable, potent, and selective topoisomerase I inhibitors without being substrates of drug efflux transporters. Mol Cancer Ther. 2007 Dec;6(12 Pt 1):3229-38. PubMed PMID: 18089716.

57: Downs LS Jr, Judson PL, Argenta PA, Ghebre R, Geller MA, Bliss RL, Boente MP, Nahhas WA, Abu-Ghazaleh SZ, Chen MD, Carson LF. A prospective randomized trial of thalidomide with topotecan compared with topotecan alone in women with recurrent epithelial ovarian carcinoma. Cancer. 2008 Jan 15;112(2):331-9. PubMed PMID: 18058810.

58: Walterhouse D, Watson A. Optimal management strategies for rhabdomyosarcoma in children. Paediatr Drugs. 2007;9(6):391-400. Review. PubMed PMID: 18052409.

59: Bernbeck B, Bahci S, Meisel R, Troeger A, Schönberger S, Laws HJ, Kramm C, Wessalowski R, Koscielniak E, Dilloo D, Göbel U. Serial intense chemotherapy combining topotecan, etoposide, carboplatin and cyclophosphamide (TECC) followed by autologous hematopoietic stem cell support in patients with high risk soft tissue sarcoma (STS). Klin Padiatr. 2007 Nov-Dec;219(6):318-22. PubMed PMID: 18050041.

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61: Sorensen M, Lassen U, Palshof T, Jensen BB, Johansen J, Jensen PB, Langer SW. Topotecan and cisplatin in combination with concurrent twice-daily chemoradiation in limited disease small cell lung cancer-a Danish Oncological Lung Cancer Group (DOLG) phase II trial. Lung Cancer. 2008 May;60(2):252-8. Epub 2007 Nov 26. PubMed PMID: 18036701.

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63: Schaiquevich P, Panetta JC, Iacono LC, Freeman BB 3rd, Santana VM, Gajjar A, Stewart CF. Population pharmacokinetic analysis of topotecan in pediatric cancer patients. Clin Cancer Res. 2007 Nov 15;13(22 Pt 1):6703-11. PubMed PMID: 18006771.

64: Ackermann S, Beckmann MW, Thiel F, Bogenrieder T. Topotecan in cervical cancer. Int J Gynecol Cancer. 2007 Nov-Dec;17(6):1215-23. Review. PubMed PMID: 17997795.

65: Reni M, Mazza E, Foppoli M, Ferreri AJ. Primary central nervous system lymphomas: salvage treatment after failure to high-dose methotrexate. Cancer Lett. 2007 Dec 18;258(2):165-70. Epub 2007 Nov 13. Review. PubMed PMID: 17993246.

66: Liao Z, Robey RW, Guirouilh-Barbat J, To KK, Polgar O, Bates SE, Pommier Y. Reduced expression of DNA topoisomerase I in SF295 human glioblastoma cells selected for resistance to homocamptothecin and diflomotecan. Mol Pharmacol. 2008 Feb;73(2):490-7. Epub 2007 Nov 5. PubMed PMID: 17984197.

67: O'Brien M, Eckardt J, Ramlau R. Recent advances with topotecan in the treatment of lung cancer. Oncologist. 2007 Oct;12(10):1194-204. Review. PubMed PMID: 17962613.

68: Fung-Kee-Fung M, Oliver T, Elit L, Oza A, Hirte HW, Bryson P. Optimal chemotherapy treatment for women with recurrent ovarian cancer. Curr Oncol. 2007 Oct;14(5):195-208. PubMed PMID: 17938703; PubMed Central PMCID: PMC2002482.

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70: Metzger ML, Stewart CF, Freeman BB 3rd, Billups CA, Hoffer FA, Wu J, Coppes MJ, Grant R, Chintagumpala M, Mullen EA, Alvarado C, Daw NC, Dome JS. Topotecan is active against Wilms' tumor: results of a multi-institutional phase II study. J Clin Oncol. 2007 Jul 20;25(21):3130-6. PubMed PMID: 17634492.

71: Bookman MA. Developmental chemotherapy and management of recurrent ovarian cancer. J Clin Oncol. 2003 May 15;21(10 Suppl):149s-167s. PubMed PMID: 17633784.

72: Long HJ 3rd. Management of metastatic cervical cancer: review of the literature. J Clin Oncol. 2007 Jul 10;25(20):2966-74. Review. PubMed PMID: 17617528.

73: Möbus V, Kieback DG, Kaubitzsch SK. Duration of chemotherapy with topotecan influences survival in recurrent ovarian cancer: a meta-analysis. Anticancer Res. 2007 May-Jun;27(3B):1581-7. PubMed PMID: 17595779.

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75: Ettinger DS. Amrubicin for the treatment of small cell lung cancer: does effectiveness cross the Pacific? J Thorac Oncol. 2007 Feb;2(2):160-5. Review. PubMed PMID: 17410034.

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78: Robey RW, Polgar O, Deeken J, To KW, Bates SE. ABCG2: determining its relevance in clinical drug resistance. Cancer Metastasis Rev. 2007 Mar;26(1):39-57. Review. PubMed PMID: 17323127.

79: Markman M. New, expanded, and modified use of approved antineoplastic agents in ovarian cancer. Oncologist. 2007 Feb;12(2):186-90. Review. PubMed PMID: 17296814.

80: Lebeau B. [Small cell lung cancer (CPC). Second line treatment]. Rev Mal Respir. 2006 Nov;23(5 Pt 3):16S205-16S208. Review. French. PubMed PMID: 17268359.

81: Azim HA Jr, Ganti AK. Treatment options for relapsed small-cell lung cancer. Anticancer Drugs. 2007 Mar;18(3):255-61. Review. PubMed PMID: 17264756.

82: Al-Faris N, Al Harbi T, Goia C, Pappo A, Doyle J, Gassas A. Does consolidation with autologous stem cell transplantation improve the outcome of children with metastatic or relapsed Ewing sarcoma? Pediatr Blood Cancer. 2007 Aug;49(2):190-5. PubMed PMID: 17262797.

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84: Randall-Whitis LM, Monk BJ. Topotecan in the management of cervical cancer. Expert Opin Pharmacother. 2007 Feb;8(2):227-36. Review. PubMed PMID: 17257092.

85: MacCallum C, Gillenwater HH. Second-line treatment of small-cell lung cancer. Curr Oncol Rep. 2006 Jul;8(4):258-64. Review. PubMed PMID: 17254525.

86: Chhatriwala H, Jafri N, Salgia R. A review of topoisomerase inhibition in lung cancer. Cancer Biol Ther. 2006 Dec;5(12):1600-7. Epub 2006 Dec 29. Review. PubMed PMID: 17224634.

87: Garst J, Herndon JE 2nd, Shafman T, Campagna L, Blackwell S, Padilla K, Bjurstrom T, Andrews C, Maravich-May D, Anderson E, Crawford J. A phase I study of dose-dense topotecan given upfront to standard therapy in patients with small cell lung cancer. Clin Drug Investig. 2006;26(5):257-66. PubMed PMID: 17163259.

88: Grønlund B. Progressive epithelial ovarian carcinoma. Prognostic factors and clinical management. Dan Med Bull. 2006 Aug;53(3):232-57. Review. PubMed PMID: 17092448.

89: Seamon JA, Rugg CA, Emanuel S, Calcagno AM, Ambudkar SV, Middleton SA, Butler J, Borowski V, Greenberger LM. Role of the ABCG2 drug transporter in the resistance and oral bioavailability of a potent cyclin-dependent kinase/Aurora kinase inhibitor. Mol Cancer Ther. 2006 Oct;5(10):2459-67. PubMed PMID: 17041089.

90: Lilenbaum RC, Huber RM, Treat J, Masters G, Kaubitzsch S, Lane S, Wissel P. Topotecan therapy in patients with relapsed small-cell lung cancer and poor performance status. Clin Lung Cancer. 2006 Sep;8(2):130-4. PubMed PMID: 17026814.

91: Gupta AA, Pappo AS. New drugs for the treatment of metastatic or refractory soft tissue sarcomas in children. Future Oncol. 2006 Oct;2(5):675-85. Review. PubMed PMID: 17026459.

92: Yamashita Y, Krauze MT, Kawaguchi T, Noble CO, Drummond DC, Park JW, Bankiewicz KS. Convection-enhanced delivery of a topoisomerase I inhibitor (nanoliposomal topotecan) and a topoisomerase II inhibitor (pegylated liposomal doxorubicin) in intracranial brain tumor xenografts. Neuro Oncol. 2007 Jan;9(1):20-8. Epub 2006 Oct 3. PubMed PMID: 17018695; PubMed Central PMCID: PMC1828110.

93: Kloft C, Wallin J, Henningsson A, Chatelut E, Karlsson MO. Population pharmacokinetic-pharmacodynamic model for neutropenia with patient subgroup identification: comparison across anticancer drugs. Clin Cancer Res. 2006 Sep 15;12(18):5481-90. PubMed PMID: 17000683.

94: Stapleton S, Blaney S. New agents for intrathecal administration. Cancer Invest. 2006 Aug-Sep;24(5):528-34. Review. PubMed PMID: 16939963.

95: Motl S, Zhuang Y, Waters CM, Stewart CF. Pharmacokinetic considerations in the treatment of CNS tumours. Clin Pharmacokinet. 2006;45(9):871-903. Review. PubMed PMID: 16928151.

96: Moore DH. Chemotherapy for recurrent cervical carcinoma. Curr Opin Oncol. 2006 Sep;18(5):516-9. Review. PubMed PMID: 16894302.

97: McGuire WP. Is it time for some new approaches for treating advanced ovarian cancer? J Natl Cancer Inst. 2006 Aug 2;98(15):1024-6. PubMed PMID: 16882933.

98: Soft Tissue Sarcoma Committee of the Children's Oncology Group, Lager JJ, Lyden ER, Anderson JR, Pappo AS, Meyer WH, Breitfeld PP. Pooled analysis of phase II window studies in children with contemporary high-risk metastatic rhabdomyosarcoma: a report from the Soft Tissue Sarcoma Committee of the Children's Oncology Group. J Clin Oncol. 2006 Jul 20;24(21):3415-22. PubMed PMID: 16849756.

99: Li QY, Zu YG, Shi RZ, Yao LP. Review camptothecin: current perspectives. Curr Med Chem. 2006;13(17):2021-39. Review. PubMed PMID: 16842195.

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106: Dubey S, Hutson P, Alberti D, Arzoomanian R, Binger K, Volkman J, Feierabend C, Wilding G, Schiller JH. Phase I study of docetaxel and topotecan in patients with advanced malignancies. J Oncol Pharm Pract. 2005 Dec;11(4):131-8. PubMed PMID: 16595064.

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113: Clark JW. Rubitecan. Expert Opin Investig Drugs. 2006 Jan;15(1):71-9. Review. PubMed PMID: 16370935.

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115: Kumar A, Wakelee H. Second- and third-line treatments in non-small cell lung cancer. Curr Treat Options Oncol. 2006 Jan;7(1):37-49. Review. PubMed PMID: 16343367.

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117: Chintagumpala MM, Friedman HS, Stewart CF, Kepner J, McLendon RE, Modrich PL, McCluggage C, Burger P, Holmes E, Thompson S, Rutka J, Michalski J, Woo S, Blaney SM, Kun LE, Horowitz ME; Pediatric Oncology Group Study. A phase II window trial of procarbazine and topotecan in children with high-grade glioma: a report from the children's oncology group. J Neurooncol. 2006 Apr;77(2):193-8. PubMed PMID: 16314955.

118: Markman M. Topotecan as second-line therapy for ovarian cancer: dosage versus toxicity. Oncologist. 2005 Oct;10(9):695-7. PubMed PMID: 16249348.

119: Armstrong DK, Spriggs D, Levin J, Poulin R, Lane S. Hematologic safety and tolerability of topotecan in recurrent ovarian cancer and small cell lung cancer: an integrated analysis. Oncologist. 2005 Oct;10(9):686-94. Review. PubMed PMID: 16249347.

120: Tewari KS, Monk BJ. Gynecologic oncology group trials of chemotherapy for metastatic and recurrent cervical cancer. Curr Oncol Rep. 2005 Nov;7(6):419-34. Review. PubMed PMID: 16221379.

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125: London WB, Chang MN. One- and two-stage designs for stratified phase II clinical trials. Stat Med. 2005 Sep 15;24(17):2597-611. PubMed PMID: 16118809.

126: Boege F. DNA topoisomerases in therapy--tenth conference. 6-8 October 1999, Amsterdam, The Netherlands. IDrugs. 1999 Dec;2(12):1275-7. PubMed PMID: 16113955.

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128: Harter P, du Bois A, Schade-Brittinger C, Burges A, Wollschlaeger K, Gropp M, Schmalfeldt B, Huober J, Staehle A, Pfisterer J. Non-enrolment of ovarian cancer patients in clinical trials: reasons and background. Ann Oncol. 2005 Nov;16(11):1801-5. Epub 2005 Aug 9. PubMed PMID: 16091427.

129: Garber K. New drugs target hypoxia response in tumors. J Natl Cancer Inst. 2005 Aug 3;97(15):1112-4. Erratum in: J Natl Cancer Inst. 2005 Sep 7;97(17):1. PubMed PMID: 16077066.

130: Turner PK, Iacono LC, Panetta JC, Santana VM, Daw NC, Gajjar A, Stewart CF. Development and validation of limited sampling models for topotecan lactone pharmacokinetic studies in children. Cancer Chemother Pharmacol. 2006 Apr;57(4):475-82. Epub 2005 Jul 27. PubMed PMID: 16047146.

131: Pentheroudakis G, Pavlidis N. Management of leptomeningeal malignancy. Expert Opin Pharmacother. 2005 Jun;6(7):1115-25. Review. PubMed PMID: 15957966.

132: Kelland LR. Emerging drugs for ovarian cancer. Expert Opin Emerg Drugs. 2005 May;10(2):413-24. Review. PubMed PMID: 15934876.

133: Mullins D, Proulx D, Saoudi A, Ng CE. Chronomodulation of topotecan or X-radiation treatment increases treatment efficacy without enhancing acute toxicity. Int J Radiat Oncol Biol Phys. 2005 May 1;62(1):230-7. PubMed PMID: 15850926.

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137: Bennett CL, Calhoun EA. Pharmacoeconomics of liposomal anthracycline therapy. Semin Oncol. 2004 Dec;31(6 Suppl 13):191-5. Review. PubMed PMID: 15717744.

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139: Murphy BA. Topoisomerases in the treatment of metastatic or recurrent squamous carcinoma of the head and neck. Expert Opin Pharmacother. 2005 Jan;6(1):85-92. Review. PubMed PMID: 15709886.

140: Dark GG, Calvert AH, Grimshaw R, Poole C, Swenerton K, Kaye S, Coleman R, Jayson G, Le T, Ellard S, Trudeau M, Vasey P, Hamilton M, Cameron T, Barrett E, Walsh W, McIntosh L, Eisenhauer EA. Randomized trial of two intravenous schedules of the topoisomerase I inhibitor liposomal lurtotecan in women with relapsed epithelial ovarian cancer: a trial of the national cancer institute of Canada clinical trials group. J Clin Oncol. 2005 Mar 20;23(9):1859-66. Epub 2005 Feb 7. PubMed PMID: 15699482.

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143: Lilenbaum RC. Treatment of patients with advanced lung cancer and poor performance status. Clin Lung Cancer. 2004 Dec;6 Suppl 2:S71-4. Review. PubMed PMID: 15638962.

144: Di Nicolantonio F, Knight LA, Whitehouse PA, Mercer SJ, Sharma S, Charlton PA, Norris D, Cree IA. The ex vivo characterization of XR5944 (MLN944) against a panel of human clinical tumor samples. Mol Cancer Ther. 2004 Dec;3(12):1631-7. PubMed PMID: 15634657.

145: Hoang-Xuan K, Camilleri-Broët S, Soussain C. Recent advances in primary CNS lymphoma. Curr Opin Oncol. 2004 Nov;16(6):601-6. Review. PubMed PMID: 15627024.

146: Stewart DJ. Topotecan in the first-line treatment of small cell lung cancer. Oncologist. 2004;9 Suppl 6:33-42. Review. PubMed PMID: 15616148.

147: Eckardt JR. Emerging role of weekly topotecan in recurrent small cell lung cancer. Oncologist. 2004;9 Suppl 6:25-32. Review. PubMed PMID: 15616147.

148: Gralla RJ. Quality-of-life considerations in patients with advanced lung cancer: effect of topotecan on symptom palliation and quality of life. Oncologist. 2004;9 Suppl 6:14-24. Review. PubMed PMID: 15616146.

149: Casas F, Jeremic B. In regard to Bogart et al.: 70 Gy thoracic radiotherapy is feasible concurrent with chemotherapy for limited-stage non-small-cell lung cancer: Analysis of cancer and leukemia group B study 39808 (Int J Radiat Oncol Biol Phys 2004;59:460-468). Int J Radiat Oncol Biol Phys. 2004 Dec 1;60(5):1661-2; author reply 1662-3. PubMed PMID: 15590201.

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151: Johnston SR. Ovarian cancer: review of the National Institute for Clinical Excellence (NICE) guidance recommendations. Cancer Invest. 2004;22(5):730-42. Review. PubMed PMID: 15581055.

152: Ozols RF. Update on Gynecologic Oncology Group (GOG) trials in ovarian cancer. Cancer Invest. 2004;22 Suppl 2:11-20. Review. PubMed PMID: 15573741.

153: Ledermann JA, Wheeler S. How should we manage patients with "platinum-sensitive" recurrent ovarian cancer? Cancer Invest. 2004;22 Suppl 2:2-10. Review. PubMed PMID: 15573740.

154: Ahmad T, Gore M. Review of the use of topotecan in ovarian carcinoma. Expert Opin Pharmacother. 2004 Nov;5(11):2333-40. Review. PubMed PMID: 15500380.

155: Rapisarda A, Zalek J, Hollingshead M, Braunschweig T, Uranchimeg B, Bonomi CA, Borgel SD, Carter JP, Hewitt SM, Shoemaker RH, Melillo G. Schedule-dependent inhibition of hypoxia-inducible factor-1alpha protein accumulation, angiogenesis, and tumor growth by topotecan in U251-HRE glioblastoma xenografts. Cancer Res. 2004 Oct 1;64(19):6845-8. PubMed PMID: 15466170.

156: Traina TA, Sabbatini P, Aghajanian C, Dupont J. Weekly topotecan for recurrent endometrial cancer: a case series and review of the literature. Gynecol Oncol. 2004 Oct;95(1):235-41. Review. PubMed PMID: 15385138.

157: Kuppens IE, Beijnen J, Schellens JH. Topoisomerase I inhibitors in the treatment of gastrointestinal cancer: from intravenous to oral administration. Clin Colorectal Cancer. 2004 Sep;4(3):163-80. Review. PubMed PMID: 15377400.

158: Ozols RF. Advanced ovarian cancer: a clinical update on first-line treatment, recurrent disease, and new agents. J Natl Compr Canc Netw. 2004 Sep;2 Suppl 2:S60-73. Review. PubMed PMID: 19780247.

159: Armstrong TS, Gilbert MR. The treatment of neoplastic meningitis. Expert Opin Pharmacother. 2004 Sep;5(9):1929-35. PubMed PMID: 15330730.

160: TLK 286. Drugs R D. 2004;5(2):116-8. Review. PubMed PMID: 15293875.

161: Cho LC, Choy H. Topoisomerase I inhibitors in the combined-modality therapy of lung cancer. Oncology (Williston Park). 2004 Jun;18(7 Suppl 4):29-39. Review. PubMed PMID: 15255165.

162: De Placido S, Scambia G, Di Vagno G, Naglieri E, Lombardi AV, Biamonte R, Marinaccio M, Cartenì G, Manzione L, Febbraro A, De Matteis A, Gasparini G, Valerio MR, Danese S, Perrone F, Lauria R, De Laurentiis M, Greggi S, Gallo C, Pignata S. Topotecan compared with no therapy after response to surgery and carboplatin/paclitaxel in patients with ovarian cancer: Multicenter Italian Trials in Ovarian Cancer (MITO-1) randomized study. J Clin Oncol. 2004 Jul 1;22(13):2635-42. PubMed PMID: 15226331.

163: Markman M, Webster K, Zanotti K, Peterson G, Kulp B, Belinson J. Survival following the documentation of platinum and taxane resistance in ovarian cancer: a single institution experience involving multiple phase 2 clinical trials. Gynecol Oncol. 2004 Jun;93(3):699-701. PubMed PMID: 15196867.

164: Ivanova A, Wang K. A non-parametric approach to the design and analysis of two-dimensional dose-finding trials. Stat Med. 2004 Jun 30;23(12):1861-70. PubMed PMID: 15195320.

165: Arndt C, Hawkins D, Anderson JR, Breitfeld P, Womer R, Meyer W. Age is a risk factor for chemotherapy-induced hepatopathy with vincristine, dactinomycin, and cyclophosphamide. J Clin Oncol. 2004 May 15;22(10):1894-901. Erratum in: J Clin Oncol. 2004 Aug 15;22(16):3434. Dosage error in article text. PubMed PMID: 15143082.

166: Reddy K. Evolving role of topotecan in treating small-cell lung cancer. Clin Lung Cancer. 2004 Mar;5(5):270-2. Review. PubMed PMID: 15086965.

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168: Sehouli J, Stengel D, Oskay G, Blohmer J, Kaubitzsch S, Lichtenegger W; Ovarian Cancer Study Group of the Nord-Ostdeutsche Gesellschaft für Gynäkologische Onkologie (NOGGO). Dose finding study for combination treatment with topotecan and gemcitabine of patients with recurrent ovarian cancer after failure of first-line chemotherapy with Paclitaxel and platinum. Onkologie. 2004 Feb;27(1):58-64. PubMed PMID: 15007250.

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171: Hu Y, Krishan A, Nie W, Sridhar KS, Mayer LD, Bally M. Synergistic cytotoxicity of pyrazoloacridine with doxorubicin, etoposide, and topotecan in drug-resistant tumor cells. Clin Cancer Res. 2004 Feb 1;10(3):1160-9. PubMed PMID: 14871996.

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181: Greco FA, Hainsworth JD. Emerging role of topotecan in first-line therapy of small-cell lung cancer. Clin Lung Cancer. 2003 Mar;4(5):279-87. PubMed PMID: 14609445.

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186: Eckardt J. Single-agent chemotherapy for non-small cell lung cancer. Lung Cancer. 2003 Aug;41 Suppl 4:S17-22. Review. PubMed PMID: 14565510.

187: von Pawel J. The role of topotecan in treating small cell lung cancer: second-line treatment. Lung Cancer. 2003 Aug;41 Suppl 4:S3-8. PubMed PMID: 14565508.

188: Holloway RW. Treatment options for endometrial cancer: experience with topotecan. Gynecol Oncol. 2003 Sep;90(3 Pt 2):S28-33. Review. PubMed PMID: 13129493.

189: Fiorica JV. The role of topotecan in the treatment of advanced cervical cancer. Gynecol Oncol. 2003 Sep;90(3 Pt 2):S16-21. Review. PubMed PMID: 13129491.

190: Stuart GC. First-line treatment regimens and the role of consolidation therapy in advanced ovarian cancer. Gynecol Oncol. 2003 Sep;90(3 Pt 2):S8-15. Review. PubMed PMID: 13129490.

191: Herzog TJ. Clinical experience with topotecan in relapsed ovarian cancer. Gynecol Oncol. 2003 Sep;90(3 Pt 2):S3-7. Review. PubMed PMID: 13129489.

192: Shepherd FA. Second-line chemotherapy for non-small cell lung cancer. Expert Rev Anticancer Ther. 2003 Aug;3(4):435-42. Review. PubMed PMID: 12934656.

193: Copeland LJ, Bookman M, Trimble E; Gynecologic Oncology Group Protocol GOG 182-ICON5. Clinical trials of newer regimens for treating ovarian cancer: the rationale for Gynecologic Oncology Group Protocol GOG 182-ICON5. Gynecol Oncol. 2003 Aug;90(2 Pt 2):S1-7. PubMed PMID: 12927999.

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195: Sargent JM, Elgie AW, Williamson CJ, Hill BT. Ex vivo effects of the dual topoisomerase inhibitor tafluposide (F 11782) on cells isolated from fresh tumor samples taken from patients with cancer. Anticancer Drugs. 2003 Jul;14(6):467-73. PubMed PMID: 12853890.

196: Sehouli J, Stengel D, Oskay G, Blohmer J, Kaubitzsch S, Lichtenegger W. A new therapeutical approach: topotecan plus gemcitabine in the treatment of patients with relapsed ovarian cancer after failure of first-line chemotherapy with paclitaxel and platinum. J Obstet Gynaecol Res. 2003 Jun;29(3):123-31. PubMed PMID: 12841693.

197: Rose PG. Combined-modality therapy of locally advanced cervical cancer. J Clin Oncol. 2003 May 15;21(10 Suppl):211s-217s. Review. PubMed PMID: 12743137.

198: Jett JR, Hatfield AK, Hillman S, Bauman MD, Mailliard JA, Kugler JW, Morton RF, Marks RS, Levitt R. Alternating chemotherapy with etoposide plus cisplatin and topotecan plus paclitaxel in patients with untreated, extensive-stage small cell lung carcinoma: a phase II trial of the North Central Cancer Treatment Group. Cancer. 2003 May 15;97(10):2498-503. PubMed PMID: 12733149.

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200: Douillard JY, Schiller J. ZD0473 combined with other chemotherapeutic agents for the treatment of solid malignancies. Eur J Cancer. 2002 Dec;38 Suppl 8:S25-31. PubMed PMID: 12645909.

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206: Grabenbauer GG, Anders K, Fietkau RJ, Klautke G, Feldmann HJ, Weiser S, Staab HJ, Krauseneck P, Sauer R. Prolonged infusional topotecan and accelerated hyperfractionated 3d-conformal radiation in patients with newly diagnosed glioblastoma--a phase I study. J Neurooncol. 2002 Dec;60(3):269-75. PubMed PMID: 12510778.

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208: Malek SN, Gore SD. Commentary: topoisomerases as targets in acute leukemia: I, II, I plus II or none? Leuk Res. 2003 Jan;27(1):1-3. PubMed PMID: 12479845.

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210: Gibson AD, D'Orazio A. VIII International Conference on malignant lymphoma. June 12-15, 2002 Lugano, Switzerland. Clin Lymphoma. 2002 Sep;3(2):75-81. PubMed PMID: 12435279.

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216: Coleman RL. Emerging role of topotecan in front-line treatment of carcinoma of the ovary. Oncologist. 2002;7 Suppl 5:46-55. Review. PubMed PMID: 12324633.

217: Fiorica JV. Update on the treatment of cervical and uterine carcinoma: focus on topotecan. Oncologist. 2002;7 Suppl 5:36-45. Review. PubMed PMID: 12324632.

218: Morris R, Munkarah A. Alternate dosing schedules for topotecan in the treatment of recurrent ovarian cancer. Oncologist. 2002;7 Suppl 5:29-35. Review. PubMed PMID: 12324631.

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