topotecan

Summary

Summary: An antineoplastic agent used to treat ovarian cancer. It works by inhibiting DNA TOPOISOMERASES, TYPE I.

Top Publications

  1. pmc The mechanism of topoisomerase I poisoning by a camptothecin analog
    Bart L Staker
    deCODE Genetics, Incorporated, BioStructures Group, 7869 Northeast Day Road West, Bainbridge Island, WA 98110, USA
    Proc Natl Acad Sci U S A 99:15387-92. 2002
  2. pmc Subconjunctival carboplatin and systemic topotecan treatment in preclinical models of retinoblastoma
    Katie M Nemeth
    Department of Developmental Neurobiology, St Jude Children s Research Hospital, Memphis, Tennessee 38105 2794, USA
    Cancer 117:421-34. 2011
  3. pmc R-loop formation at Snord116 mediates topotecan inhibition of Ube3a-antisense and allele-specific chromatin decondensation
    Weston T Powell
    Medical Microbiology and Immunology, Genome Center, Medical Investigation of Neurodevelopmental Disorders Institute, and Department of Molecular and Cellular Biology, University of California, Davis, CA 95616, USA
    Proc Natl Acad Sci U S A 110:13938-43. 2013
  4. pmc Phase I study of PARP inhibitor ABT-888 in combination with topotecan in adults with refractory solid tumors and lymphomas
    Shivaani Kummar
    Center for Cancer Research and Division of Cancer Treatment and Diagnosis, National Cancer Institute, Bethesda, USA
    Cancer Res 71:5626-34. 2011
  5. ncbi Antitumour drugs impede DNA uncoiling by topoisomerase I
    Daniel A Koster
    Kavli Institute of Nanoscience, Faculty of Applied Sciences, Delft University of Technology, Lorentzweg 1, 2628 CJ Delft, The Netherlands
    Nature 448:213-7. 2007
  6. ncbi Phase I/II study of AT-101 with topotecan in relapsed and refractory small cell lung cancer
    Rebecca Suk Heist
    Massachusetts General Hospital, Boston, Massachusetts 02114, USA
    J Thorac Oncol 5:1637-43. 2010
  7. pmc Structural and dynamical effects induced by the anticancer drug topotecan on the human topoisomerase I - DNA complex
    Giordano Mancini
    CASPUR Inter University Consortium for the Application of Super Computing for Universities and Research, Rome, Italy
    PLoS ONE 5:e10934. 2010
  8. pmc Multihistology, target-driven pilot trial of oral topotecan as an inhibitor of hypoxia-inducible factor-1α in advanced solid tumors
    Shivaani Kummar
    Center for Cancer Research and Division of Cancer Treatment and Diagnosis, National Cancer Institute, Bethesda, MD 21702, USA
    Clin Cancer Res 17:5123-31. 2011
  9. pmc A chemical screen identifies the chemotherapeutic drug topotecan as a specific inhibitor of the B-MYB/MYCN axis in neuroblastoma
    Francesco Sottile
    UCL Institute of Child Health, London, UK
    Oncotarget 3:535-45. 2012
  10. ncbi Topotecan combination chemotherapy in two new rodent models of retinoblastoma
    Nikia A Laurie
    Department of Developmental Neurobiology and Pharmaceutical Sciences, St Jude Children s Research Hospital, Memphis, Tennessee 38105, USA
    Clin Cancer Res 11:7569-78. 2005

Research Grants

  1. MECHANISM OF ACTION OF ANTITUMOR DRUGS
    Leroy F Liu; Fiscal Year: 2013
  2. Synthesis, Biosynthesis, and Structure of Antitumor Agents
    Thomas R Hoye; Fiscal Year: 2013
  3. The 50th Annual Meeting of the American Society of Pharmacognosy
    Bill J Baker; Fiscal Year: 2010
  4. Mayo Clinic SPORE in Ovarian Cancer
    Scott H Kaufmann; Fiscal Year: 2013
  5. Mechanism of Drug Transport by BCRP/ABCG2
    Qingcheng Mao; Fiscal Year: 2010
  6. Pharmacogenetics in children with high-risk neuroblastoma
    Jeannine S McCune; Fiscal Year: 2013
  7. IGF1R gene 3'UTR variants in high-risk pediatric neuroblastoma
    Andrei Thomas-Tikhonenko; Fiscal Year: 2013
  8. Regulation of Supercoil Unwinding by Topoisomerase 1B
    BREEANA GROGAN ANDERSON; Fiscal Year: 2013
  9. Anticancer Drug Pharmacology in Very Young Children
    Clinton F Stewart; Fiscal Year: 2013
  10. Episcleral Chemotherapy as Salvage Therapy for Eyes with Retinoblastoma
    RICARDO A CARVALHO; Fiscal Year: 2010

Detail Information

Publications270 found, 100 shown here

  1. pmc The mechanism of topoisomerase I poisoning by a camptothecin analog
    Bart L Staker
    deCODE Genetics, Incorporated, BioStructures Group, 7869 Northeast Day Road West, Bainbridge Island, WA 98110, USA
    Proc Natl Acad Sci U S A 99:15387-92. 2002
    ..topoisomerase I covalently joined to double-stranded DNA and bound to the clinically approved anticancer agent Topotecan. Topotecan mimics a DNA base pair and binds at the site of DNA cleavage by intercalating between the upstream (-..
  2. pmc Subconjunctival carboplatin and systemic topotecan treatment in preclinical models of retinoblastoma
    Katie M Nemeth
    Department of Developmental Neurobiology, St Jude Children s Research Hospital, Memphis, Tennessee 38105 2794, USA
    Cancer 117:421-34. 2011
    The authors demonstrated previously that the combination of topotecan (TPT) and carboplatin (CBP) was more effective than current chemotherapeutic combinations used to treat retinoblastoma in an orthotopic xenograft model...
  3. pmc R-loop formation at Snord116 mediates topotecan inhibition of Ube3a-antisense and allele-specific chromatin decondensation
    Weston T Powell
    Medical Microbiology and Immunology, Genome Center, Medical Investigation of Neurodevelopmental Disorders Institute, and Department of Molecular and Cellular Biology, University of California, Davis, CA 95616, USA
    Proc Natl Acad Sci U S A 110:13938-43. 2013
    ..Interestingly, topoisomerase inhibitors, including topotecan, were recently identified in an unbiased drug screen for compounds that could reverse the silent paternal allele ..
  4. pmc Phase I study of PARP inhibitor ABT-888 in combination with topotecan in adults with refractory solid tumors and lymphomas
    Shivaani Kummar
    Center for Cancer Research and Division of Cancer Treatment and Diagnosis, National Cancer Institute, Bethesda, USA
    Cancer Res 71:5626-34. 2011
    A phase I trial of ABT-888 (veliparib), a PARP inhibitor, in combination with topotecan, a topoisomerase I-targeted agent, was carried out to determine maximum tolerated dose (MTD), safety, pharmacokinetics, and pharmacodynamics of the ..
  5. ncbi Antitumour drugs impede DNA uncoiling by topoisomerase I
    Daniel A Koster
    Kavli Institute of Nanoscience, Faculty of Applied Sciences, Delft University of Technology, Lorentzweg 1, 2628 CJ Delft, The Netherlands
    Nature 448:213-7. 2007
    ..Camptothecins, such as topotecan, induce cell death by poisoning DNA topoisomerase I, an enzyme capable of removing DNA supercoils...
  6. ncbi Phase I/II study of AT-101 with topotecan in relapsed and refractory small cell lung cancer
    Rebecca Suk Heist
    Massachusetts General Hospital, Boston, Massachusetts 02114, USA
    J Thorac Oncol 5:1637-43. 2010
    AT-101 is an oral, pan Bcl-2 family protein inhibitor that has demonstrated activity in small cell lung cancer (SCLC) models. A phase I/II study was conducted combining AT-101 with topotecan in relapsed and refractory SCLC.
  7. pmc Structural and dynamical effects induced by the anticancer drug topotecan on the human topoisomerase I - DNA complex
    Giordano Mancini
    CASPUR Inter University Consortium for the Application of Super Computing for Universities and Research, Rome, Italy
    PLoS ONE 5:e10934. 2010
    ..It is the only target of the camptothecin family of anticancer drugs. Among these, topotecan has been used to treat lung and ovarian carcinoma for several years...
  8. pmc Multihistology, target-driven pilot trial of oral topotecan as an inhibitor of hypoxia-inducible factor-1α in advanced solid tumors
    Shivaani Kummar
    Center for Cancer Research and Division of Cancer Treatment and Diagnosis, National Cancer Institute, Bethesda, MD 21702, USA
    Clin Cancer Res 17:5123-31. 2011
    ..b>Topotecan, a topoisomerase I inhibitor, has been shown to inhibit HIF-1α expression in preclinical models...
  9. pmc A chemical screen identifies the chemotherapeutic drug topotecan as a specific inhibitor of the B-MYB/MYCN axis in neuroblastoma
    Francesco Sottile
    UCL Institute of Child Health, London, UK
    Oncotarget 3:535-45. 2012
    ..the topoisomerase-1 inhibitor camptothecin, is of considerable clinical interest since its derivatives topotecan and irinotecan are currently used as first and second line treatment agents for various types of cancer, ..
  10. ncbi Topotecan combination chemotherapy in two new rodent models of retinoblastoma
    Nikia A Laurie
    Department of Developmental Neurobiology and Pharmaceutical Sciences, St Jude Children s Research Hospital, Memphis, Tennessee 38105, USA
    Clin Cancer Res 11:7569-78. 2005
    ..two models combined with pharmacokinetic studies and cell culture experiments, we have tested the efficacy of topotecan combined with carboplatin and of topotecan combined with vincristine for the treatment of retinoblastoma...
  11. ncbi Advanced ovarian cancer: phase III randomized study of sequential cisplatin-topotecan and carboplatin-paclitaxel vs carboplatin-paclitaxel
    P Hoskins
    BC Cancer Agency, Vancouver Clinic, 600 West 10 Ave, Vancouver, BC, Canada V5Z 4E6
    J Natl Cancer Inst 102:1547-56. 2010
    b>Topotecan has single-agent activity in recurrent ovarian cancer. It was evaluated in a novel combination compared with standard frontline therapy.
  12. ncbi Combined weekly topotecan and biweekly bevacizumab in women with platinum-resistant ovarian, peritoneal, or fallopian tube cancer: results of a phase 2 study
    Kathryn F McGonigle
    Women s Cancer Care of Seattle, Seattle, Washington 98133, USA
    Cancer 117:3731-40. 2011
    A phase 2 trial was conducted to determine the toxicity and efficacy of combined weekly topotecan and biweekly bevacizumab in patients with primary or secondary platinum-resistant ovarian, peritoneal, or fallopian tube cancer (OC).
  13. pmc Phase II trial of lapatinib and topotecan (LapTop) in patients with platinum-refractory/resistant ovarian and primary peritoneal carcinoma
    S John Weroha
    Department of Medical Oncology, Mayo, Rochester, MN 55905, USA
    Gynecol Oncol 122:116-20. 2011
    ..One purported mechanism of topotecan resistance is the breast cancer resistance protein (BCRP) and P-glycoprotein (Pgp)...
  14. ncbi P-glycoprotein and breast cancer resistance protein: two dominant transporters working together in limiting the brain penetration of topotecan
    Nienke A de Vries
    Department of Clinical Chemistry, The Netherlands Cancer Institute Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands
    Clin Cancer Res 13:6440-9. 2007
    ..Whereas the effect of P-glycoprotein (P-gp) at the BBB is well established, the role of breast cancer resistance protein (BCRP) that is also expressed at the BBB is not...
  15. ncbi Randomized phase II study of lapatinib plus capecitabine or lapatinib plus topotecan for patients with HER2-positive breast cancer brain metastases
    Nancy U Lin
    Division of Women s Cancers, Department of Medical Oncology, Dana Farber Cancer Institute, 450 Brookline Avenue, Boston, MA 02215, USA
    J Neurooncol 105:613-20. 2011
    ..22 of a planned 110 patients were enrolled due to excess toxicity and lack of efficacy in the lapatinib plus topotecan arm...
  16. ncbi Pilot study of topotecan and high-dose cyclophosphamide for resistant pediatric solid tumors
    B H Kushner
    Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, New York 10021, USA
    Med Pediatr Oncol 35:468-74. 2000
    The recommended dosages of topotecan and cyclophosphamide in combination for prior-treated patients-3...
  17. ncbi Topotecan and cyclophosphamide in patients with refractory or relapsed Ewing tumors
    Andrea Hunold
    Department of Pediatric Hematology and Oncology, University Children s Hospital, Muenster, Germany
    Pediatr Blood Cancer 47:795-800. 2006
    ..Promising response rates have recently been reported for the combination of topotecan (TOPO) and cyclophosphamide (CYC) encouraging wider application of this combination in patients with relapsed ..
  18. ncbi Cyclophosphamide plus topotecan in children with recurrent or refractory solid tumors: a Pediatric Oncology Group phase II study
    R L Saylors
    University of Arkansas for Medical Sciences, Little Rock, AR, USA
    J Clin Oncol 19:3463-9. 2001
    PURPOSE: To determine the response rate of the combination of cyclophosphamide and topotecan in pediatric patients with recurrent or refractory malignant solid tumors...
  19. ncbi A phase II study of metronomic oral topotecan for recurrent childhood brain tumors
    Jane E Minturn
    Division of Oncology, The Children s Hospital of Philadelphia, University of Pennsylvania, Philadelphia, Pennsylvania, USA
    Pediatr Blood Cancer 56:39-44. 2011
    The prognosis for recurrent or refractory brain tumors in children is poor with conventional therapies. Topotecan is a topoisomerase I inhibitor with good central nervous system (CNS) penetration following oral administration...
  20. ncbi Phase III trial comparing supportive care alone with supportive care with oral topotecan in patients with relapsed small-cell lung cancer
    Mary E R O'Brien
    Royal Marsden Hospital, National Health System Trust, Sutton, Surrey, England
    J Clin Oncol 24:5441-7. 2006
    ..For patients with small-cell lung cancer (SCLC), further chemotherapy is routinely considered at relapse after first-line therapy. However, proof of clinical benefit has not been documented...
  21. pmc A phase I study of obatoclax mesylate, a Bcl-2 antagonist, plus topotecan in solid tumor malignancies
    Paul K Paik
    Thoracic Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
    Cancer Chemother Pharmacol 66:1079-85. 2010
    ..the safety, maximum tolerated dose (MTD), recommended phase II dose, and preliminary antitumor activity of obatoclax mesylate (GX15-070MS), a Bcl-2 antagonist, in combination with topotecan in patients with solid tumor malignancies.
  22. ncbi Randomized phase III trial of cisplatin with or without topotecan in carcinoma of the uterine cervix: a Gynecologic Oncology Group Study
    Harry J Long
    Mayo Clinic College of Medicine, Rochester, MN, USA
    J Clin Oncol 23:4626-33. 2005
    On the basis of reported activity of methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC) or topotecan plus cisplatin in advanced cervix cancer, we undertook a randomized trial comparing these combinations versus cisplatin alone, ..
  23. pmc Metronomic oral topotecan prolongs survival and reduces liver metastasis in improved preclinical orthotopic and adjuvant therapy colon cancer models
    Christina Hackl
    Department of Medical Biophysics, Molecular and Cellular Biology Research, Sunnybrook Research Institute, University of Toronto, Toronto, Ontario, Canada
    Gut 62:259-71. 2013
    ..In this study, the authors report the establishment of such standardised orthotopic mouse models of colon cancer and their use in evaluating metronomic topotecan alone or in combination with standard chemotherapy.
  24. pmc The inhibition of autophagy sensitises colon cancer cells with wild-type p53 but not mutant p53 to topotecan treatment
    Dan Dan Li
    State Key Laboratory of Oncology in South China, Cancer Center, Sun Yat Sen University, Guangzhou, Guangdong, People s Republic of China
    PLoS ONE 7:e45058. 2012
    b>Topotecan produces DNA damage that induces autophagy in cancer cells. In this study, sensitising topotecan to colon cancer cells with different P53 status via modulation of autophagy was examined.
  25. ncbi Pheophorbide a is a specific probe for ABCG2 function and inhibition
    Robert W Robey
    Cancer Therapeutics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Building 10, Rm 12C203, 9000 Rockville Pike, Bethesda, MD 20892, USA
    Cancer Res 64:1242-6. 2004
    ..In 4-day cytotoxicity assays, ABCG2-mediated resistance to SN-38 and topotecan was abrogated in ABCG2-transfected HEK-293 cells treated with 1 micro M tariquidar, and ABCG2-transfected cells ..
  26. ncbi Subunit-dependent inhibition and potentiation of 5-HT3 receptor by the anticancer drug, topotecan
    Yukiko Nakamura
    Department of Neuroscience and Cell Biology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan
    J Neurochem 125:7-15. 2013
    ..In this study, we show that the anticancer drug, topotecan, bidirectionally modulates the 5-HT3 receptor using a two-electrode voltage clamp technique...
  27. pmc A phase III trial of topotecan and whole brain radiation therapy for patients with CNS-metastases due to lung cancer
    T Neuhaus
    Johanniter Krankenhaus, Bonn, Germany
    Br J Cancer 100:291-7. 2009
    ..multicentric phase III trial, comparing whole brain radiation therapy (WBRT; 20 x 2 Gy) alone with WBRT+topotecan (RCT; 0.4 mg m(-2) day(-1) x 20)...
  28. ncbi Torque and dynamics of linking number relaxation in stretched supercoiled DNA
    John F Marko
    Department of Physics and Astronomy, Northwestern University, Evanston, Illinois 60208, USA
    Phys Rev E Stat Nonlin Soft Matter Phys 76:021926. 2007
    ..Such enzymes must display a breaking of symmetry between relaxations driven by equal magnitude but opposite direction torques...
  29. ncbi A phase I study of weekly temsirolimus and topotecan in the treatment of advanced and/or recurrent gynecologic malignancies
    Sarah M Temkin
    Department of Ob Gyn, Division of Gynecologic Oncology, The University of Maryland Medical School, 11 S Paca Street, Suite 300B, Baltimore, MD 21201, USA
    Gynecol Oncol 117:473-6. 2010
    The mTOR inhibitor, temsirolimus, has clinical activity in the treatment of gynecologic malignancies, particularly endometrial cancer. We sought to determine the tolerability of the combination of weekly topotecan with weekly temsirolimus.
  30. ncbi Successful therapy of subcutaneously growing human hepatoblastoma xenografts with topotecan
    S W Warmann
    Department of Pediatric Surgery, Medical School Hannover, Carl Neuberg Str 1, 30625 Hannover, Germany
    Med Pediatr Oncol 37:449-54. 2001
    ..The aim of this study was to investigate the therapeutic effects of topotecan, a water-soluble camptothecin analog (topoisomerase-I-antagonist), in an in vivo model of three human ..
  31. ncbi Cytostatic and cytotoxic effects of topotecan decoded by a novel mathematical simulation approach
    Monica Lupi
    Biophysics Unit, Laboratory of Anticancer Pharmacology, Department of Oncology, Istituto di Ricerche Farmacologiche Mario Negri, Milano, Italy
    Cancer Res 64:2825-32. 2004
    b>Topotecan (TPT) is a topoisomerase I inhibitor, and like the other drugs of this family, it is believed to act in a specific way on cells in S phase at the time of treatment...
  32. ncbi Synergistic antitumor effect between vorinostat and topotecan in small cell lung cancer cells is mediated by generation of reactive oxygen species and DNA damage-induced apoptosis
    Francesca Bruzzese
    Experimental Pharmacology Unit, Department of Research, Istituto Nazionale Tumori, Napoli, Italy
    Mol Cancer Ther 8:3075-87. 2009
    The topoisomerase-I (topo-I) inhibitor topotecan, derivative of camptothecin, is the only registered drug for relapsed small cell lung cancer (SCLC)...
  33. ncbi Clinical relevance of human cancer xenografts as a tool for preclinical assessment: example of in-vivo evaluation of topotecan-based chemotherapy in a panel of human small-cell lung cancer xenografts
    Fariba Nemati
    Department of Translational Research, Institut Curie, Paris, France
    Anticancer Drugs 21:25-32. 2010
    ..relevance of a panel of human SCLC xenografts established in our laboratory using one compromising drug in SCLC, topotecan (TPT)...
  34. ncbi The effect of PEG coating on in vitro cytotoxicity and in vivo disposition of topotecan loaded liposomes in rats
    S Dadashzadeh
    Department of Pharmaceutics, School of Pharmacy, Shaheed Beheshti Medical University, Tehran, Iran
    Int J Pharm 353:251-9. 2008
    ..In order to investigate the effect of PEG coating on in vitro and in vivo characteristics of topotecan loaded liposomes, an amphoteric anticancer drug, PEGylated and conventional liposomes were prepared by lipid ..
  35. ncbi A phase I study of concurrent weekly topotecan and cisplatin chemotherapy with whole pelvic radiation therapy in locally advanced cervical cancer: a gynecologic oncology group study
    Peter G Rose
    Case Western Reserve University, Cleveland, OH 44195, USA
    Gynecol Oncol 125:158-62. 2012
    To determine the maximum tolerated dose (MTD) and acute dose-limiting toxicities (DLT) of intravenous topotecan administered with weekly cisplatin during pelvic radiation therapy in patients with locally advanced cervical cancer.
  36. ncbi Resistance to TRAIL-induced apoptosis in ovarian cancer cell lines is overcome by co-treatment with cytotoxic drugs
    Sandra Tomek
    Department of Medicine I, University Hospital Vienna, Vienna, Austria
    Gynecol Oncol 94:107-14. 2004
    ..TRAIL, tumor necrosis factor-related apoptosis-inducing ligand, is a recently identified cytokine that preferentially kills transformed cells while sparing most normal cells...
  37. ncbi Enhancement of the fraction of the active form of an antitumor drug topotecan via an injectable hydrogel
    Guangtao Chang
    Key Laboratory of Molecular Engineering of Polymers, Ministry of Education, Department of Macromolecular Science, Laboratory of Advanced Materials, Fudan University, Shanghai, China
    J Control Release 156:21-7. 2011
    ..acid-co-glycolic acid) (PLGA-PEG-PLGA) hydrogels were tried as implants to encapsulate antitumor drug topotecan (TPT), a derivative of camptothecin (CPT)...
  38. pmc Chloroquine enhances the cytotoxicity of topotecan by inhibiting autophagy in lung cancer cells
    Yao Wang
    State Key Laboratory of Oncology in South China, Guangdong, People s Republic of China
    Chin J Cancer 30:690-700. 2011
    ..Here, we examined the relevant mechanisms by which the multipotent CQ enhanced the cytotoxicity of topotecan (TPT)...
  39. pmc Mrp4 confers resistance to topotecan and protects the brain from chemotherapy
    Markos Leggas
    Department of Pharmaceutical Sciences, St Jude Children s Research Hospital, 332 N Lauderdale, Memphis, TN 38105 2794, USA
    Mol Cell Biol 24:7612-21. 2004
    ..Unexpectedly, these mice showed enhanced accumulation of the anticancer agent topotecan in brain tissue and cerebrospinal fluid (CSF)...
  40. ncbi Randomized phase III trial of topotecan following carboplatin and paclitaxel in first-line treatment of advanced ovarian cancer: a gynecologic cancer intergroup trial of the AGO-OVAR and GINECO
    Jacobus Pfisterer
    Klinik fur Gynakologie und Geburtshilfe, Campus Kiel, Universitatsklinikum Schleswig Holstein, Michaelisstr 16, D 24105 Kiel, Germany
    J Natl Cancer Inst 98:1036-45. 2006
    ..We performed a prospective randomized phase III study to examine whether sequential administration of topotecan can improve the efficacy of carboplatin and paclitaxel in first-line treatment of advanced epithelial ovarian ..
  41. ncbi Characterization of PEGylated nanoliposomes co-remotely loaded with topotecan and vincristine: relating structure and pharmacokinetics to therapeutic efficacy
    Daniel Zucker
    Department of Biochemistry and Molecular Biology, IMRIC, The Hebrew University Hadassah Medical School, Jerusalem 91120, Israel
    J Control Release 160:281-9. 2012
    ..We encapsulated the combination of vincristine (VCR) and topotecan (TPT) in the same nanoliposome (LipoViTo)...
  42. ncbi Antitumor effect of suberoylanilide hydroxamic acid and topotecan in renal cancer cells
    Akinori Sato
    Department of Urology, National Defense Medical College, Tokorozawa, Saitama, Japan
    Oncol Res 19:217-23. 2011
    ..Recently, the combination of SAHA and topoisomerase I inhibitor, topotecan, was shown to be effective, but this treatment strategy has not been tested in renal cancer cells...
  43. ncbi A novel method to load topotecan into liposomes driven by a transmembrane NH₄EDTA gradient
    Yuehui Yang
    Shengjing Hospital of China Medical University, Shenyang, China
    Eur J Pharm Biopharm 80:332-9. 2012
    ..In this study, we intended to encapsulate topotecan within liposome adopting transmembrane NH(4)EDTA gradient in order to increase the antitumor activity and ..
  44. ncbi Development of topotecan loaded lipid nanoparticles for chemical stabilization and prolonged release
    L G Souza
    Laboratory of Pharmaceutical Technology, Federal University of Goias, Goiania, Brazil
    Eur J Pharm Biopharm 79:189-96. 2011
    b>Topotecan is an important cytotoxic drug that has gained broad acceptance in clinical use for the treatment of refractory ovarian and small-cell lung cancer...
  45. ncbi Regression of recurrent malignant gliomas with convection-enhanced delivery of topotecan
    Jeffrey N Bruce
    Department of Neurological Surgery, Columbia University Medical Center, New York, New York 10032, USA
    Neurosurgery 69:1272-9; discussion 1279-80. 2011
    ..This allows high local concentrations of drug while overcoming the limitations imposed by toxicity and the blood-brain barrier in systemic therapies that prevent the use of many potentially effective drugs...
  46. ncbi Topotecan Weekly Versus Conventional 5-Day Schedule in Patients With Platinum-Resistant Ovarian Cancer: a randomized multicenter phase II trial of the North-Eastern German Society of Gynecological Oncology Ovarian Cancer Study Group
    Jalid Sehouli
    Department of Gynecology and Oncology, Charite University Medical Center, Berlin, Germany
    J Clin Oncol 29:242-8. 2011
    Weekly administration of topotecan (Tw) is less toxic and widely considered a better treatment option than conventional 5-day therapy (Tc) in women with platinum-resistant recurrent ovarian cancer...
  47. ncbi Pharmacology of topoisomerase I inhibitors irinotecan (CPT-11) and topotecan
    Ron H J Mathijssen
    Department of Medical Oncology, Rotterdam Cancer Institute Daniel den Hoed Kliniek and University Hospital Rotterdam, PO Box 5201, Rotterdam, 3008 AE, The Netherlands
    Curr Cancer Drug Targets 2:103-23. 2002
    b>Topotecan and irinotecan (CPT-11) are both anticancer agents active in the inhibition of topoisomerase I, an enzyme involved in DNA replication and RNA transcription...
  48. ncbi Bone marrow and tumor cell colony-forming units and human tumor xenograft efficacy of noncamptothecin and camptothecin topoisomerase I inhibitors
    Leslie S Kurtzberg
    Genzyme Corporation, 49 New York Avenue, Framingham, MA 01701, USA
    Mol Cancer Ther 7:3212-22. 2008
    ..One of these, ARC-111, was compared with two clinically used camptothecins, topotecan and irinotecan/SN-38...
  49. ncbi 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 H Schiller
    University of Wisconsin Hospital and Clinics, Madison, WI 53792, USA
    J Clin Oncol 19:2114-22. 2001
    To determine the efficacy of topotecan in combination with standard chemotherapy in previously untreated patients with extensive-stage small-cell lung cancer (SCLC), the Eastern Cooperative Oncology Group (ECOG) conducted a phase III ..
  50. pmc Vincristine, actinomycin, and cyclophosphamide compared with vincristine, actinomycin, and cyclophosphamide alternating with vincristine, topotecan, and cyclophosphamide for intermediate-risk rhabdomyosarcoma: children's oncology group study D9803
    Carola A S Arndt
    Department of Pediatric and Adolescent Medicine, Mayo Clinic, Rochester, MN 55905, USA
    J Clin Oncol 27:5182-8. 2009
    ..rhabdomyosarcoma (RMS) treated with standard VAC (vincristine, dactinomycin, and cyclophosphamide) chemotherapy to that of patients treated with VAC alternating with vincristine, topotecan, and cyclophosphamide (VAC/VTC).
  51. ncbi Weekly paclitaxel as a single agent or in combination with carboplatin or weekly topotecan in patients with resistant ovarian cancer: the CARTAXHY randomized phase II trial from Groupe d'Investigateurs Nationaux pour l'Etude des Cancers Ovariens (GINECO)
    A Lortholary
    Oncology Department, Centre Catherine de Sienne, Nantes, France
    Ann Oncol 23:346-52. 2012
    Platinum rechallenge or weekly topotecan in combination have not been evaluated in randomized trials for resistant recurrent ovarian cancer (ROC).
  52. ncbi The effect of low pH on breast cancer resistance protein (ABCG2)-mediated transport of methotrexate, 7-hydroxymethotrexate, methotrexate diglutamate, folic acid, mitoxantrone, topotecan, and resveratrol in in vitro drug transport models
    Pauline Breedveld
    Department of Experimental Therapy, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands
    Mol Pharmacol 71:240-9. 2007
    ..4, is efficiently transported by BCRP at pH 6.0, whereas we did not detect active transport at pH 7.4. We conclude that BCRP transports substrate drugs more efficiently at low pH, independent of the dissociation status of the substrate...
  53. pmc Successful local regional therapy with topotecan of intraperitoneally growing human ovarian carcinoma xenografts
    G Pratesi
    Division of Experimental Oncology B, Istituto Nazionale per lo Studio e la Cura dei Tumori, Milan, Italy
    Br J Cancer 71:525-8. 1995
    The therapeutic effects of intraperitoneal topotecan, a water-soluble camptothecin analogue, were investigated in two models of human ovarian carcinoma xenografted intraperitoneally into nude mice: the IGROV-1 tumour, which originated ..
  54. pmc Bridging the gap between cytotoxic and biologic therapy with metronomic topotecan and pazopanib in ovarian cancer
    William M Merritt
    Departments of Gynecologic Oncology and Cancer Biology, The University of Texas M D Anderson Cancer Center, Unit 1362, PO Box 301439, Houston, TX 77230 1439, USA
    Mol Cancer Ther 9:985-95. 2010
    ..aimed to investigate the antitumor and antiangiogenic effects utilizing a novel therapy regimen of metronomic topotecan and pazopanib, a multireceptor tyrosine kinase inhibitor...
  55. pmc Phase II randomized comparison of topotecan plus cyclophosphamide versus topotecan alone in children with recurrent or refractory neuroblastoma: a Children's Oncology Group study
    Wendy B London
    Division of Hematology Oncology, Children s Hospital Boston Dana Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA
    J Clin Oncol 28:3808-15. 2010
    Single-agent topotecan (TOPO) and combination topotecan and cyclophosphamide (TOPO/CTX) were compared in a phase II randomized trial in relapsed/refractory neuroblastoma...
  56. ncbi Repeated injections of PEGylated liposomal topotecan induces accelerated blood clearance phenomenon in rats
    Yanling Ma
    School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, China
    Eur J Pharm Sci 45:539-45. 2012
    ..Nevertheless, in the present study, we report that a first injection of the PEGylated liposomal topotecan (a cell cycle-specific drug for the S phase) still produced a strong ABC phenomenon...
  57. ncbi Topotecan in patients with advanced neuroendocrine tumors: a phase II study with significant hematologic toxicity
    Stephen M Ansell
    Divisions of Hematology, Mayo Clinic, 200 First Street SW, Rochester, Minnesota 55905, USA
    Am J Clin Oncol 27:232-5. 2004
    ..We therefore conducted a phase II study of topotecan (TOPA) 1.5 mg/m2/d for 5 days every 3 weeks in 22 patients with advanced carcinoid and islet cell tumors...
  58. ncbi Cetuximab, topotecan and cisplatin for the treatment of advanced cervical cancer: A phase II GINECO trial
    J E Kurtz
    Hopital Civil, Strasbourg, France
    Gynecol Oncol 113:16-20. 2009
    Cisplatin (Cp) plus topotecan (Tc) is the first combination chemotherapy to demonstrate a survival advantage over cisplatin alone in advanced cervical cancer...
  59. ncbi Sensitivity and acquired resistance of BRCA1;p53-deficient mouse mammary tumors to the topoisomerase I inhibitor topotecan
    Serge A L Zander
    Division of Molecular Biology, The Netherlands Cancer Institute, 1066CX Amsterdam, The Netherlands
    Cancer Res 70:1700-10. 2010
    ..a genetically engineered mouse model for BRCA1-associated breast cancer, using the topoisomerase I (Top1) poison topotecan as monotherapy and in combination with poly(ADP-ribose) polymerase inhibition by olaparib...
  60. ncbi Review role of topotecan in gynaecological cancers: current indications and perspectives
    Domenica Lorusso
    Division of Gynecologic Oncology, Catholic University of the Sacred Heart, Largo Agostino Gemelli 8, IT 00168 Rome, Italy
    Crit Rev Oncol Hematol 74:163-74. 2010
    ..The aim of this article is to review the role of topotecan (Hycamtin), a semi-synthetic alkaloid derivative of camptothecin, in ovarian and cervical cancer in monotherapy ..
  61. ncbi Topotecan, cyclophosphamide, and etoposide (TCE) in the treatment of high-risk neuroblastoma. Results of a phase-II trial
    Thorsten Simon
    Children s Hospital, Department of Pediatric Oncology and Hematology, University of Cologne, Kerpener Strasse 62, 50924 Cologne, Germany
    J Cancer Res Clin Oncol 133:653-61. 2007
    Relapsed high-risk neuroblastoma patients still have a poor prognosis. This phase-II trial assessed a new topotecan containing chemotherapy approach in patients with active disease.
  62. pmc Potent preclinical impact of metronomic low-dose oral topotecan combined with the antiangiogenic drug pazopanib for the treatment of ovarian cancer
    Kae Hashimoto
    Toronto, ON M4N 3M5, Canada
    Mol Cancer Ther 9:996-1006. 2010
    ..We therefore tested an oral topoisomerase-1 inhibitor, oral topotecan, at optimal biological dose of 1 mg/kg/d...
  63. ncbi Dual-targeting topotecan liposomes modified with tamoxifen and wheat germ agglutinin significantly improve drug transport across the blood-brain barrier and survival of brain tumor-bearing animals
    Ju Du
    School of Pharmaceutical Sciences, Peking University, Beijing, China
    Mol Pharm 6:905-17. 2009
    ..b>Topotecan was then loaded into the above liposomes...
  64. ncbi Breast cancer resistance protein is localized at the plasma membrane in mitoxantrone- and topotecan-resistant cell lines
    G L Scheffer
    Department of Pathology, Free University Hospital, Amsterdam, The Netherlands
    Cancer Res 60:2589-93. 2000
    ..BCRP was detected in BCRP-transfected cells and in several mitoxantrone- and topotecan-selected tumor cell sublines...
  65. ncbi Expression of Bcl-xL in ovarian carcinoma is associated with chemoresistance and recurrent disease
    Jennifer Williams
    Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Michigan Comprehensive Cancer Center, 1500 East Medical Center Drive, Ann Arbor, MI 48109, USA
    Gynecol Oncol 96:287-95. 2005
    ....
  66. ncbi Phase II study of topotecan plus cranial radiation for glioblastoma multiforme: results of Radiation Therapy Oncology Group 9513
    Barbara Fisher
    Department of Radiation Oncology, London Regional Cancer Centre, London, Ontario, Canada
    Int J Radiat Oncol Biol Phys 53:980-6. 2002
    ..Therapy Oncology Group (RTOG) to compare the survival of patients with glioblastoma multiforme treated with topotecan combined with standard cranial radiotherapy (RT) for matched patients treated in prior RTOG studies...
  67. ncbi Optimization of vincristine-topotecan combination--paving the way for improved chemotherapy regimens by nanoliposomes
    Daniel Zucker
    Department of Biochemistry, IMRIC, The Hebrew University Hadassah Medical School, Jerusalem, Israel
    J Control Release 146:326-33. 2010
    ..The combination of topotecan (TPT) and vincristine (VCR) was selected...
  68. pmc Pilot induction regimen incorporating pharmacokinetically guided topotecan for treatment of newly diagnosed high-risk neuroblastoma: a Children's Oncology Group study
    Julie R Park
    Seattle Children s Hospital, 4800 Sandpoint Way NE, Mailstop B6553, Seattle, WA 98105, USA
    J Clin Oncol 29:4351-7. 2011
    To assess the feasibility of adding dose-intensive topotecan and cyclophosphamide to induction therapy for newly diagnosed high-risk neuroblastoma (HRNB).
  69. ncbi The role of topotecan in the treatment of brain metastases
    Eric T Wong
    Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, USA
    Oncologist 9:68-79. 2004
    ..b>Topotecan, a novel topoisomerase I inhibitor, freely crosses the blood-brain barrier and may be clinically effective in ..
  70. ncbi A phase I, randomized, open-label, parallel-cohort, dose-finding study of elacridar (GF120918) and oral topotecan in cancer patients
    Isa E L M Kuppens
    Division of Clinical Pharmacology, Department of Medical Oncology, Antoni van Leeuwenhoek Hospital The Netherlands Cancer Institute, Amsterdam, The Netherlands
    Clin Cancer Res 13:3276-85. 2007
    Breast cancer resistance protein (ABCG2) substantially limits the oral bioavailability of topotecan. Coadministration with elacridar, an inhibitor of breast cancer resistance protein-mediated drug transport, increases the bioavailability ..
  71. ncbi BCRP/MXR/ABCP expression in topotecan-resistant human breast carcinoma cells
    C H Yang
    Department of Oncology, National Taiwan University Hospital and the Graduate Institute of Medicine, Medical College, National Taiwan University, Taipei
    Biochem Pharmacol 60:831-7. 2000
    We have previously described a mitoxantrone-resistant MCF7 cell line that is cross-resistant to topotecan, 7-ethyl-10-[4-(1-piperidino)-1-piperidino]carbonyloxy-camptothecin (CPT-11), and 9-aminocamptothecin, but not to camptothecin...
  72. ncbi The mouse Bcrp1/Mxr/Abcp gene: amplification and overexpression in cell lines selected for resistance to topotecan, mitoxantrone, or doxorubicin
    J D Allen
    Division of Experimental Therapy, The Netherlands Cancer Institute, Amsterdam
    Cancer Res 59:4237-41. 1999
    Mouse fibroblast cell lines lacking functional Mdr1a, Mdr1b, and Mrp1 genes were selected for resistance to topotecan, mitoxantrone, or doxorubicin...
  73. ncbi Prospective trial on topotecan salvage therapy in primary CNS lymphoma
    L Fischer
    Department of Haematology, Oncology and Transfusion Medicine, Charite Universitatsmedizin Berlin, Campus Benjamin Franklin, Germany
    Ann Oncol 17:1141-5. 2006
    Standard salvage therapy has not been established for recurrent primary central nervous system lymphoma (PCNSL). We report the final results of a prospective study on topotecan chemotherapy in relapsed or refractory PCNSL.
  74. ncbi Assessment of histone H2AX phosphorylation induced by DNA topoisomerase I and II inhibitors topotecan and mitoxantrone and by the DNA cross-linking agent cisplatin
    Xuan Huang
    Brander Cancer Research Institute, New York Medical College, Valhalla, New York 10532, USA
    Cytometry A 58:99-110. 2004
    ..The purpose of this study was to further characterize the drug-induced (DI) IF of gammaH2AX, and in particular to distinguish it from AA gammaH2AX IF triggered by DNA breaks that occur in the course of AA DNA fragmentation...
  75. ncbi Randomized phase II trial of single-agent amrubicin or topotecan as second-line treatment in patients with small-cell lung cancer sensitive to first-line platinum-based chemotherapy
    Robert Jotte
    Rocky Mountain Cancer Centers, 10103 Ridgegate Pkwy G 01, Lone Tree, CO 80124, USA
    J Clin Oncol 29:287-93. 2011
    This phase II study evaluated the safety and efficacy of single-agent amrubicin versus topotecan in patients with small-cell lung cancer (SCLC) sensitive to first-line platinum-based chemotherapy.
  76. ncbi Long-term follow-up results of the combination of topotecan and cytarabine and other intensive chemotherapy regimens in myelodysplastic syndrome
    Hagop Kantarjian
    Department of Leukemia, University of Texas M D Anderson Cancer Center, Houston, Texas 77230, USA
    Cancer 106:1099-109. 2006
    ..Patients with MDS are often older and may have contraindications to anthracycline-based regimens. Topotecan-cytarabine regimens have shown encouraging results in higher-risk MDS...
  77. ncbi Extending the platinum-free interval in recurrent ovarian cancer: the role of topotecan in second-line chemotherapy
    M A Bookman
    Department of Medical Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111, USA
    Oncologist 4:87-94. 1999
    ..b>Topotecan is the most extensively studied agent currently available for management of recurrent ovarian cancer and has ..
  78. ncbi Topotecan is a substrate for multidrug resistance associated protein 4
    Quan Tian
    Department of Pharmacy, Faculty of Science, National University of Singapore, Singapore 117543
    Curr Drug Metab 7:105-18. 2006
    b>Topotecan (TPT) is a semisynthetic water-soluble derivative of camptothecin (CPT) used as second-line therapy in patients with metastatic ovarian carcinoma, small cell lung cancer, and other malignancies...
  79. pmc Prolonged intracerebral convection-enhanced delivery of topotecan with a subcutaneously implantable infusion pump
    Adam M Sonabend
    Department of Neurological Surgery, Columbia University Medical Center, New York, New York, USA
    Neuro Oncol 13:886-93. 2011
    ..To evaluate the feasibility of prolonged topotecan administration by CED in a large animal brain with the use of a subcutaneous implantable pump...
  80. ncbi Three-drug intra-arterial chemotherapy using simultaneous carboplatin, topotecan and melphalan for intraocular retinoblastoma: preliminary results
    Brian P Marr
    Ophthalmic Oncology Service, Memorial Sloan Kettering Cancer Center, New York, NY 10021, USA
    Br J Ophthalmol 96:1300-3. 2012
    To report outcomes with selective intra-arterial chemotherapy (SIAC) using simultaneous carboplatin, topotecan, and melphalan for advanced intraocular retinoblastoma.
  81. ncbi Safety and tolerability of the poly(ADP-ribose) polymerase (PARP) inhibitor, olaparib (AZD2281) in combination with topotecan for the treatment of patients with advanced solid tumors: a phase I study
    Jens Samol
    St George s Hospital, Blackshaw Rd, London, UK
    Invest New Drugs 30:1493-500. 2012
    The aim of this phase I study was to determine the safety and tolerability and to establish the maximum tolerated dose (MTD) of orally administered olaparib (AZD2281) in combination with topotecan in patients with advanced solid tumors.
  82. ncbi Convection-enhanced delivery of topotecan into diffuse intrinsic brainstem tumors in children
    Richard C E Anderson
    Departments of Neurosurgery, Columbia University, College of Physicians and Surgeons, New York, NY 10032, USA
    J Neurosurg Pediatr 11:289-95. 2013
    ..In this report the authors describe CED of the topoisomerase inhibitor topotecan for the treatment of DIPG in 2 children...
  83. pmc Characterisation of a human small-cell lung cancer cell line resistant to the DNA topoisomerase I-directed drug topotecan
    M Sorensen
    Department of Pathology, Sundby Hospital, Copenhagen, Denmark
    Br J Cancer 72:399-404. 1995
    Camptothecins are DNA topoisomerase I-directed anti-tumour drugs with a novel mechanism of action. Topotecan (TPT), a hydrophilic derivative of camptothecin, is currently undergoing phase II clinical trials in small-cell lung cancer (..
  84. ncbi Population pharmacokinetic and adverse event analysis of topotecan in patients with solid tumors
    Diane R Mould
    Projections Research Inc, 535 Springview Lane, Phoenixville, PA 19460, USA
    Clin Pharmacol Ther 71:334-48. 2002
    Our objective was to describe the pharmacokinetics and pharmacodynamics of topotecan in patients.
  85. ncbi Clinical use of topoisomerase I inhibitors in anticancer treatment
    C Rodriguez-Galindo
    Department of Hematology Oncology, St Jude Children s Research Hospital, Memphis, Tennessee 38105 2794, USA
    Med Pediatr Oncol 35:385-402. 2000
    The camptothecin analogs topotecan and irinotecan have shown to be among the most effective anticancer agents and, as S-phase specific agents, their antitumor effect is maximized when they are administered in protracted schedules...
  86. ncbi Ex vivo stimulation of renal transport of the cytostatic drugs methotrexate, cisplatin, topotecan (Hycamtin) and raltitrexed (Tomudex) by dexamethasone, T3 and EGF in intact human and rat kidney tissue and in human renal cell carcinoma
    C Fleck
    Institute of Pharmacology and Toxicology, University of Jena, 07740 Jena, Germany
    Urol Res 30:256-62. 2002
    ..or not accumulation of the anticancer drugs methotrexate (MTX), cisplatin (CP), raltitrexed (Tomudex) and topotecan (Hycamtin) can be increased in intact, healthy rat and human renal cortical slices and in human renal cell ..
  87. pmc Metronomic oral topotecan with pazopanib is an active antiangiogenic regimen in mouse models of aggressive pediatric solid tumor
    Sushil Kumar
    Division of Hematology and Oncology, Department of Pediatrics, The Hospital for Sick Children, Toronto, Canada
    Clin Cancer Res 17:5656-67. 2011
    ..We have tested the efficacies of daily oral LDM topotecan alone and in combination with pazopanib, a VEGF receptor inhibitor, in three pediatric extracranial solid tumor ..
  88. pmc Topotecan in patients with BRCA-associated and sporadic platinum-resistant ovarian, fallopian tube, and primary peritoneal cancers
    David M Hyman
    Gynecologic Medical Oncology Service, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
    Gynecol Oncol 123:196-9. 2011
    To evaluate the efficacy of topoisomerase I inhibitor, topotecan, in patients with recurrent BRCA+ versus BRCA- ovarian, fallopian tube, and primary peritoneal carcinomas.
  89. ncbi Topotecan and ifosfamide systemic chemotherapy for CNS involvement of solid tumors
    Philipp Kiewe
    Department of Hematology, Charite Universitatsmedizin Berlin, Campus Benjamin Franklin, Hindenburgdamm 30, 12200 Berlin, Germany
    J Neurooncol 103:629-34. 2011
    ..Here, we report on the efficacy and toxicity of topotecan/ifosfamide (TOPO/IFO) combination chemotherapy in patients treated for CNS involvement of different solid ..
  90. ncbi Topotecan combined with carboplatin in recurrent epithelial ovarian cancer: results of a single-institutional phase II study
    Heeseok Kang
    Department of Obstetrics and Gynecology, Medical Foundation Baek Song, Good Morning Hospital, Kyungki do, Republic of Korea
    Gynecol Oncol 114:210-4. 2009
    The aim of this trial was to investigate the efficacy and toxicity of a relative high-dose of topotecan combined with carboplatin in recurrent or persistent epithelial ovarian cancer (EOC).
  91. ncbi [131I]MIBG and topotecan: a rationale for combination therapy for neuroblastoma
    Anthony G McCluskey
    Targeted Therapy Group and Department of Child Health, Cancer Research UK Beatson Laboratories, University of Glasgow, Garscube Estate, Glasgow G61 1BD, UK
    Cancer Lett 228:221-7. 2005
    ..However, long-term cure remains elusive, and the topoisomerase I inhibitor topotecan may improve upon existing [131I]MIBG therapy...
  92. ncbi Episcleral implants for topotecan delivery to the posterior segment of the eye
    Angel M Carcaboso
    Department of Pharmacology, University of Buenos Aires, Buenos Aires, Argentina
    Invest Ophthalmol Vis Sci 51:2126-34. 2010
    Purpose. Intravenous or periocular topotecan has been proposed as new treatment modality for patients with advanced intraocular retinoblastoma, but systemic topotecan lactone exposure induced by both approaches may cause toxicity...
  93. ncbi Phase 2 trial of prolonged administration of oral topotecan in platinum/taxane-refractory ovarian, fallopian tube, and primary peritoneal cancers
    Maurie Markman
    Department of Hematology Medical Oncology, The Cleveland Clinic Foundation, Cleveland, OH 44195, USA
    Gynecol Oncol 95:109-13. 2004
    ..and clinical data have demonstrated the importance of schedule in optimizing the cytotoxic potential of topotecan, one of the most active agents in ovarian cancer...
  94. pmc Reversal of MDR1-associated resistance to topotecan by PAK-200S, a new dihydropyridine analogue, in human cancer cell lines
    U Vanhoefer
    Department of Internal Medicine Cancer Research, West German Cancer Center, University of Essen Medical School, Germany
    Br J Cancer 81:1304-10. 1999
    ..of the membrane P170-glycoprotein (P-gp) may confer resistance to the topoisomerase-I-interactive agent topotecan. The present study describes the cellular effects of a new dihydropyridine analogue, PAK-200S, on P-gp-mediated ..
  95. ncbi Topotecan central nervous system penetration is altered by a tyrosine kinase inhibitor
    Yanli Zhuang
    Department of Pharmaceutical Sciences, St Jude Children s Research Hospital, University of Tennessee Health Science Center, Memphis, Tennessee 38105, USA
    Cancer Res 66:11305-13. 2006
    A potential strategy to increase the efficacy of topotecan to treat central nervous system (CNS) malignancies is modulation of the activity of ATP-binding cassette (ABC) transporters at the blood-brain and blood-cerebrospinal fluid ..
  96. pmc Plasma and cerebrospinal fluid pharmacokinetics of topotecan in a phase I trial of topotecan, tamoxifen, and carboplatin, in the treatment of recurrent or refractory brain or spinal cord tumors
    Robert J Morgan
    Department of Medical Oncology and Therapeutics Research, City of Hope Comprehensive Cancer Center, Duarte, CA, 91010, USA
    Cancer Chemother Pharmacol 66:927-33. 2010
    ..toxicities (DLT) and maximally tolerated doses of the combination of fixed-dose tamoxifen and carboplatin, with escalating doses of topotecan, and to determine the pharmacokinetics of topotecan in the plasma and cerebrospinal fluid.
  97. ncbi Phase II study of topotecan and cyclophosphamide in patients with relapsed and refractory multiple myeloma
    Eric H Kraut
    Leuk Res 29:1233-4. 2005
  98. ncbi Sorafenib in combination with weekly topotecan in recurrent ovarian cancer, a phase I/II study of the Hoosier Oncology Group
    R Ramasubbaiah
    Indiana University Melvin and Bren Simon Cancer Center, Indianapolis, IN, USA
    Gynecol Oncol 123:499-504. 2011
    This trial determined the efficacy and tolerability of sorafenib and weekly topotecan in patients with platinum-resistant ovarian cancer (OC) or primary peritoneal carcinomatosis (PPC).
  99. ncbi Synergistic cytotoxicity of pyrazoloacridine with doxorubicin, etoposide, and topotecan in drug-resistant tumor cells
    YanPing Hu
    Department of Advanced Therapeutics, British Columbia Cancer Agency, 601 West 10th Avenue, Vancouver, BC, Canada V5Z 1L3
    Clin Cancer Res 10:1160-9. 2004
    ..In the present study, the cytotoxic effects of PZA combined with doxorubicin, topotecan, and etoposide were determined using paired parental and doxorubicin-resistant human colon carcinoma (SW-620 and ..
  100. ncbi Periocular topotecan for intraocular retinoblastoma
    Ashwin C Mallipatna
    Departments of Ophthalmology and Visual Sciences, The Hospital for Sick Children, Ontario, Canada
    Arch Ophthalmol 129:738-45. 2011
    To review the effectiveness and toxicity of periocular topotecan hydrochloride in fibrin sealant (Tisseel) for the control of intraocular retinoblastoma.
  101. ncbi Combination of cytarabine and topotecan in patients treated for acute myeloid leukemia with persistent disease after frontline induction
    Thomas Prebet
    Department of Hematology, Institut Paoli Calmettes, Marseille, France
    Leuk Lymphoma 53:2186-91. 2012
    ..We hypothesized that use of a topotecan and cytarabine combination in this setting might improve tolerance and efficacy...

Research Grants64

  1. MECHANISM OF ACTION OF ANTITUMOR DRUGS
    Leroy F Liu; Fiscal Year: 2013
    ..Camptothecins (CPTs) (e.g. irinotecan and topotecan), the prototypic Top1-targeting drugs, have been developed into the clinic...
  2. Synthesis, Biosynthesis, and Structure of Antitumor Agents
    Thomas R Hoye; Fiscal Year: 2013
    ..from daunomycin), etoposide/teniposide (from podophyllotoxin), irinotecan/topotecan (from camptothecin), mitomycin, mylotarg (from calicheamicin), streptozotocin, taxol (and docetaxel), ..
  3. The 50th Annual Meeting of the American Society of Pharmacognosy
    Bill J Baker; Fiscal Year: 2010
    ..natural products which are in use in the clinic or which are investigational drugs are taxol, etoposide, topotecan/irinotecan, the halichondrin analog E7389, dolastatin derivatives, the anthracyclines and the epothilones, to ..
  4. Mayo Clinic SPORE in Ovarian Cancer
    Scott H Kaufmann; Fiscal Year: 2013
    ..studies the effect of the poly(ADP-ribose) polymerase (PARP) inhibitor ABT-888 alone and In combination with topotecan. In addition to elucidating how ABT-888 converts PARP Into an enzyme that actively contributes to the demise of ..
  5. Mechanism of Drug Transport by BCRP/ABCG2
    Qingcheng Mao; Fiscal Year: 2010
    ..of BCRP in cancer cells is associated with resistance to multiple anticancer drugs, including mitoxantrone, topotecan, and flavopiridol...
  6. Pharmacogenetics in children with high-risk neuroblastoma
    Jeannine S McCune; Fiscal Year: 2013
    ..transporters involved in the production and elimination of 4HCY are associated with response to a dose-intense topotecan/cyclophosphamide (topoCY) induction regimen in children with newly diagnosed high-risk neuroblastoma...
  7. IGF1R gene 3'UTR variants in high-risk pediatric neuroblastoma
    Andrei Thomas-Tikhonenko; Fiscal Year: 2013
    ..and contrast responses of rs3833015 and rs374251 tumors to conventional therapeutics (cyclophosphamide and topotecan) and IGF1R inhibitors...
  8. Regulation of Supercoil Unwinding by Topoisomerase 1B
    BREEANA GROGAN ANDERSON; Fiscal Year: 2013
    ..Human Topo-DNA covalent complex forms the sole target for the widely used anticancer drugs irinotecan and topotecan, which disrupt supercoil unwinding...
  9. Anticancer Drug Pharmacology in Very Young Children
    Clinton F Stewart; Fiscal Year: 2013
    ..PK), pharmacogenetic, and pharmacodynamic (PD) studies of methotrexate (MTX), cyclophosphamide (CTX), and topotecan (TPT) as part of a clinical protocol that treats infants and young children with malignant brain tumors...
  10. Episcleral Chemotherapy as Salvage Therapy for Eyes with Retinoblastoma
    RICARDO A CARVALHO; Fiscal Year: 2010
    ..funds requested will support Phase I and Phase II clinical trials of episcleral formulations of carboplatin and topotecan in eyes of children with advanced intraocular retinoblastoma (all IND enabling studies and clinical supplies are ..
  11. Targeting of Bladder Tumor Cells by Nanocarriers Bearing bacillus Calmette-Guerin
    Claudio Aguilar; Fiscal Year: 2013
    ..Here, we will test the hypothesis that multivalency and membrane fusogenic properties of topotecan-loaded FAP-nanocarriers control their uptake and cytotoxicity, respectively...
  12. Optimization of dipeptide-linked benzimidazole topoisomerase 1 poisons
    Craig Beeson; Fiscal Year: 2009
    ..class of poisons and should generally exhibit reduced toxicity compared to the CPT- class of agents such as topotecan. Structural insights from Top1-DNA crystal structures were used to design a small library of N-acetyl dipeptides ..
  13. Anti-Cancer Drug Design Targeting Human Topoisomerase I
    Lance Stewart; Fiscal Year: 2002
    ..0 angstrom structural information of Topotecan bound to the human topo I-DNA covalent complex...
  14. DRUG SEQUENCING RESISTANCE IN MULTIPLE MYELOMA
    Daniel Sullivan; Fiscal Year: 1999
    ..1. To establish the toxicity and potential efficacy of a high-dose regimen sequenced as melphalan followed by topotecan followed by VP-16 phosphate (MTV) followed by peripheral blood stem cell rescue in the treatment of multiple ..
  15. Aerosol Delivery of Lung Cancer Drugs
    Brian Hansen; Fiscal Year: 2002
    ..Many of the agents that exhibit inhibitory activity towards cancer cell growth are lipophilic, including topotecan, taxol, taxotere, and etoposide...
  16. A novel diagnostic test for Irinotecan and Topotecan sensitivity
    Ruth A Gjerset; Fiscal Year: 2013
    ..to a widely used class of chemotherapeutic agents derived from camptothecin that includes Irinotecan and Topotecan. The assay will be based on a novel biomarker associated with cellular sensitivity to camptothecin and will have ..
  17. EGRF Targeting of Therapeutic Liposomes for Treating Gliobastoma
    CHARLES DAVID JAMES; Fiscal Year: 2010
    The studies we are proposing will compare epidermal growth factor receptor (EGFR) targeted liposome- formulated topotecan (EGFR-LFT) vs...
  18. Benzo[i]phenanthridines: TOP1-Targeting Antitumor Agents
    EDMOND LAVOIE; Fiscal Year: 2006
    ..Despite these shortcomings, there are two derivatives of CPT (Irinotecan, and Topotecan) in clinical use...
  19. NEW MECHANISMS OF MULTIDRUG RESISTANCE IN CANCER CELLS
    Erasmus Schneider; Fiscal Year: 2001
    ..selected for mitoxantrone resistance, exhibits unusual cross-resistance to several camptothecin analogs such as topotecan and irinotecan...
  20. MECHANISM BASED PHASE I TRIAL OF TOPOTECAN IN LEUKEMIA
    Brenda Cooper; Fiscal Year: 2000
    Description: (Applicant's Abstract) Topotecan, a novel chemotherapeutic agent that targets the DNA metabolizing enzyme topoisomerase I has shown activity in patients with relapsed, refractory leukemia, and myelodysplastic syndromes...
  21. Novel Therapies for High-Risk Neuroblastoma
    Julie Park; Fiscal Year: 2006
    ..b>Topotecan has shown promising anti-leuroblasotma activity and has synergistic activity with standard agents used in the ..
  22. Improved Use of Camptothecins for Small Cell Lung Cancer
    John Murren; Fiscal Year: 2004
    ..showed that down-regulation of topo I occurs in peripheral mononuclear cells in vivo following treatment with topotecan. As a result, the first aim of this proposal will be to perform a phase I and pharmacokinetic study to establish ..
  23. NF-KB MEDIATED DRUG RESISTANCE IN OVARIAN CANCER
    David Spriggs; Fiscal Year: 2004
    ..The effect of NF-kappaB activation on resistance to the cytotoxicity of CDDP paclitaxel, melphalan, doxorubicin, topotecan and other agents will be examined...
  24. Topoisomerase Targeting and Resistance in Leukemia
    Eric Rubin; Fiscal Year: 2003
    ..The recent development of topotecan as a topoisomerase I-targeting drug that is active in the therapy of leukemia allows investigation of rationally ..
  25. CHRONIC CONVECTION ENHANCED DELIVERY (CED) OF TOPOTECAN FOR GLIOBLASTOMA
    Jeffrey N Bruce; Fiscal Year: 2013
    ..We have shown in a Phase 1 clinical trial that a topoisomerase inhibitor, topotecan, can be safely and effectively delivered by convection enhanced delivery into patients with recurrent malignant ..
  26. Role of HSulf-1 Loss in Apoptosis and Drug Resistance
    Viji Shridhar; Fiscal Year: 2007
    ..results in resistance to other agents commonly used to treat ovarian cancer, including paclitaxel, topotecan, gemcitabine and doxorubicin, in vitro and in vivo and 4) evaluate the relationship between HSulf-1 expression ..
  27. PHASE II TRIALS OF TOPO I INHIBITORS
    Nathan Berger; Fiscal Year: 2000
    ..Topoisomerase I inhibitors to be studied in these protocols will include topotecan, CPT-11 and 9-aminocamptothecin...
  28. TRIALS OF CLADRIBINE PLUS OTHER AGENTS FOR PEDIATRIC AML
    Clinton Stewart; Fiscal Year: 2000
    ..in the therapy of previously untreated patients, and the other a Phase I study of the combination of 2-CDA with topotecan. The primary objectives of the former study are: 1) to evaluate the activity and toxicity of the combination of ..
  29. Aerosol Therapy for Lung Cancer
    Brian Hansen; Fiscal Year: 2007
    ..New formulations of anticancer drugs (topotecan, paclitaxel, taxotere, etoposide and vitamine E succinate) were developed for the new system...
  30. TOPOTECAN BY INTRACEREBRAL CLYSIS FOR BRAIN TUMORS
    Jeffrey Bruce; Fiscal Year: 2006
    ..Our preliminary data has shown that glioma cells are sensitive to topoisomerase I inhibitors including topotecan at levels that can be achieved in vivo with ICC...
  31. Potent Topoisomerase I Inhibition For Glioma Therapy
    Thomas Burke; Fiscal Year: 2001
    ..analog that displays superior blood stability relative to the FDA-approved camptothecin congeners, topotecan and CPT- 11. DB-67 also exhibits a high degree of anti-cancer potency both in vitro and in vivo...
  32. ABC Transporters in CNS Penetration of Camptothecins
    Christopher Waters; Fiscal Year: 2007
    ..Camptothecin analogs such as topotecan and irinotecan are used to treat children with primary CNS tumors, but the CNS distribution of these drugs is ..
  33. DNA Minor Groove-Targeting Anticancer Agents
    DANIEL PILCH; Fiscal Year: 2006
    ..potent TOP1 poisoning activities and cytotoxicities exceeding that of the clinical camptothecin derivative, topotecan. However, the specific molecular interactions that govern the TOP1 poisoning and cytotoxic activities of the TBs ..
  34. NOVEL A RING AND E RING MODIFIED CAMPTOTHECIN ANALOGS
    Daniel Von Hoff; Fiscal Year: 2001
    ..In 1996, two campothecin (CPT) analogs received regulatory approval for use in patients with solid malignancies: topotecan for previous treated patients with advanced ovarian cancer, and CPT-11 (Irinotecan) for patients with advanced ..
  35. SYNTHESIS OF INDOLOCARBAZOLES AS TOPOISOMERASE I POISONS
    David Zembower; Fiscal Year: 2000
    ..Such as agent could be used alone or in combination with existing antitumor agents, especially in patients who develop resistance to existing medications. ..
  36. OPTIMIZED CANCER CHEMOTHERAPY VIA PHARMACODYNAMIC MODELS
    James Gallo; Fiscal Year: 2000
    ..e. MYLS) data including patient covariates to evaluate PD models for topotecan's (TPT's) MYLS, both as a single agent and in combination...
  37. MECHANISMS OF ACTION AND RESISTANCE TO ICRF187
    Jack Yalowich; Fiscal Year: 2000
    ..inhibition of topo II will upregulate DNA topoisomerase I levels and sensitize cells to inhibitors such as topotecan. Results obtained will establish more precisely the mechanism of action of drugs that inhibit topo II without ..
  38. DETACHMENT SENSITIZES CELLS TO TOPOISOMERASE INHIBITORS
    Cecilia Whitacre; Fiscal Year: 2001
    ..This hypothesis is based on previous observations that show sensitization of cells to topotecan by interference with cell adhesion in vitro...
  39. IN VITRO CORRELATES OF DRUG SENSITIVITY IN LUNG CANCER
    Bonnie Glisson; Fiscal Year: 1993
    ..We will focus on topotecan, the first topoisomerase I-targeted drug to be tested extensively in the clinic in the U.S...
  40. Changes in Tumor DNA Methylation with Decitabine
    David Stewart; Fiscal Year: 2006
    ..This preliminary look at individual genes may provide a molecular rationale for future decitabine therapeutic studies in specific relevant tumor types. ..
  41. Pharmacodynamics of Gemcitabine by MRS in Pancreatic CA
    Howard Hochster; Fiscal Year: 2008
    ..unreadable] [unreadable]..
  42. DENDRITIC CELL THERAPY OF CHRONIC MYELOGENOUS LEUKEMIA
    Mark Litzow; Fiscal Year: 2003
    ..The combined data will provide a comprehensive understanding of the interaction of the immune system and CML and will yield information required for the rational design of more effective clinical protocols in the future. ..
  43. PEDIATRIC BRAIN TUMOR RESEARCH CENTER
    Susan Blaney; Fiscal Year: 2003
    ..It offers leadership in the development of new agents, in new uses of sophisticated radiotherapy, and in the application of new approaches to brain tumor therapy. ..
  44. Mentored Research in Ovarian Cancer
    Michael Seiden; Fiscal Year: 2006
    ..The P.l.'s dual role as a clinical research director and laboratory P.I. provides fertile opportunity for translation between the clinic and the laboratory. [unreadable] [unreadable] [unreadable] [unreadable]..
  45. Phase I Clinical Trials of Anti-Cancer Agents
    Francis Giles; Fiscal Year: 2007
    ..abstract_text> ..
  46. CHILDRENS CANCER GROUP
    Peter Steinherz; Fiscal Year: 2002
    ..Members of the affiliate hospitals have been participating in CCG studies and have proven their ability to conduct the clinical studies and provide material for laboratory evaluation. ..
  47. INTERACTIONS OF P GLYCOPROTEIN WITH CYTOCHROME P4503A
    Erin Schuetz; Fiscal Year: 2001
    ....
  48. Ribosome-based Single Molecule Method to Acquire Sequence Data from Genomes
    Wlodek Mandecki; Fiscal Year: 2010
    ..The method can be used for nucleic acid diagnostics in vitro and in drug discovery. ..
  49. Biomarker modulation/COX-2 inhibitor/Breast Cancer
    Banu Arun; Fiscal Year: 2003
    ..Ultimately, the development of non-hormonal chemoprevention agents, and identification of surrogate markers will allow us to plan large-scale, phase III chemoprevention studies with the endpoint of cancer incidence. ..
  50. TOPOISOMERASE I INHIBITORS IN LEUKEMIA AND SOLID TUMORS
    Scott H Kaufmann; Fiscal Year: 2010
    DESCRIPTION (provided by applicant): Two topoisomerase I (topo I) poisons, topotecan (TPT) and irinotecan (CPT-11), are approved for use in the U.S.;and additional topo I poisons are currently undergoing clinical testing...
  51. ATR in Human Cancer and Anticancer Therapy
    William Cliby; Fiscal Year: 2004
    ..Using xenograft models we will develop a gene therapy model of ATR disruption to test the safety and efficacy of targeting ATR for anticancer therapy. ..
  52. Cell-based Assay on Microtransponders
    Wlodek Mandecki; Fiscal Year: 2004
    ..The benefits of the program involve the advancement of cell-based assay technology, acceleration of drug discovery programs in research laboratories and pharmaceutical industry, and cost savings. ..
  53. Ovarian Cancer: Strategies for consolidation
    Paul Sabbatini; Fiscal Year: 2006
    ..Promising strategies will be moved to patients in primary remission (Specific Aim 1) with a current median time to treatment failure of 18-21 months...
  54. HEPATIC DRUG ELIMINATION IN PREGNANCY
    Mary Vore; Fiscal Year: 2007
    ..unreadable] [unreadable] [unreadable] [unreadable] [unreadable] [unreadable]..
  55. Pregnane X Receptor: Regulation and Pharmacogenomics
    Erin Schuetz; Fiscal Year: 2007
    ..In total this proposal describes a comprehensive set of experiments to determine how PXR is regulated. ..
  56. Antifolate Resistance in Osteosarcoma
    Richard Gorlick; Fiscal Year: 2007
    ....
  57. Ubc9 as a novel target for cancer therapy
    Yin Yuan Mo; Fiscal Year: 2006
    ..As a result, we will be able to develop valuable Ubc9-based anticancer agents [unreadable] [unreadable]..
  58. A Phase 2 Trial of Dasatinib in Patients with NSCLC and Acquired Resistance to Er
    Vincent Miller; Fiscal Year: 2008
    ..The proposed work is a clinical trial to determine whether dasatinib is an effective treatment for patients with NSCLC and acquired resistance to erlotinib or gefitinib. [unreadable] [unreadable] [unreadable]..
  59. Modulating P-glycoprotein to Enhance Neurodegenerative Drug Penetration of Brain
    CHRISTINE HRYCYNA; Fiscal Year: 2008
    ..Completion of these studies has the potential to improve treatment of epilepsy and Alzheimer's disease. [unreadable] [unreadable] [unreadable]..
  60. Molecular Determinants of Acquired Erlotinib Resistance
    Vincent Miller; Fiscal Year: 2006
    ..abstract_text> ..
  61. Role of Proteases in Therapy-Induced Apoptosis
    Scott H Kaufmann; Fiscal Year: 2010
    ..Collectively, these studies are designed to improve current understanding of the biology of death ligand-induced apoptosis and provide new information that should be helpful in designing more effective cancer treatments. ..
  62. Strategies Against HPV Related Genital Diseases in Women
    Bradley Monk; Fiscal Year: 2006
    ..It is expected that Dr. Monk will have obtained extramural funding for both his laboratory and clinical studies by the end of the period of support requested. ..
  63. Tumor metastasis: Biobehavioral mechanisms
    Anil K Sood; Fiscal Year: 2009
    ....
  64. Hospice Pain Control: Developing an Opioid Order Sheet
    Barbara Murphy; Fiscal Year: 2006
    ..Once the modifications lave been made, we will conduct a pilot study to assess feasibility, utility and efficacy of the order sheet in the outpatient hospice setting. [unreadable] [unreadable]..