Skip to main content
PMC home page
British Journal of Cancer logoLink to British Journal of Cancer
. 1997;76(7):952–962. doi: 10.1038/bjc.1997.491

Topoisomerase I inhibitors: the relevance of prolonged exposure for present clinical development.

C J Gerrits 1, M J de Jonge 1, J H Schellens 1, G Stoter 1, J Verweij 1
PMCID: PMC2228255  PMID: 9328159

Abstract

Topoisomerase I inhibitors constitute a new class of anti-cancer agents. Recently, topotecan and irinotecan were registered for clinical use in ovarian cancer and colorectal cancer respectively. Cytotoxicity of topoisomerase I inhibitors is S-phase specific, and in vitro and in vivo studies have suggested that, for efficacy, prolonged exposure might be more important than short-term exposure to high concentration. Clinical development of those topoisomerase I inhibitors that have reached this stage is also focused on schedules aiming to achieve prolonged exposure. In this review, we summarize all published preclinical studies on this topic for topoisomerase I inhibitors in clinical development, namely 20-S-camptothecin, 9-nitro-camptothecin, 9-amino-camptothecin, topotecan, irinotecan and GI147211. In addition, preliminary data on clinical studies concerning this topic are also reviewed. The data suggest that prolonged exposure may indeed be relevant for anti-tumour activity. However, the optimal schedule is yet to be determined. Finally, clinical data are yet too immature to draw definitive conclusions.

Full text

PDF
952

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Aller P., Rius C., Mata F., Zorrilla A., Cabañas C., Bellón T., Bernabeu C. Camptothecin induces differentiation and stimulates the expression of differentiation-related genes in U-937 human promonocytic leukemia cells. Cancer Res. 1992 Mar 1;52(5):1245–1251. [PubMed] [Google Scholar]
  2. Andoh T., Ishii K., Suzuki Y., Ikegami Y., Kusunoki Y., Takemoto Y., Okada K. Characterization of a mammalian mutant with a camptothecin-resistant DNA topoisomerase I. Proc Natl Acad Sci U S A. 1987 Aug;84(16):5565–5569. doi: 10.1073/pnas.84.16.5565. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Blaney S. M., Balis F. M., Cole D. E., Craig C., Reid J. M., Ames M. M., Krailo M., Reaman G., Hammond D., Poplack D. G. Pediatric phase I trial and pharmacokinetic study of topotecan administered as a 24-hour continuous infusion. Cancer Res. 1993 Mar 1;53(5):1032–1036. [PubMed] [Google Scholar]
  4. Bruno S., Giaretti W., Darzynkiewicz Z. Effect of camptothecin on mitogenic stimulation of human lymphocytes: involvement of DNA topoisomerase I in cell transition from G0 to G1 phase of the cell cycle and in DNA replication. J Cell Physiol. 1992 Jun;151(3):478–486. doi: 10.1002/jcp.1041510306. [DOI] [PubMed] [Google Scholar]
  5. Burris H. A., 3rd, Awada A., Kuhn J. G., Eckardt J. R., Cobb P. W., Rinaldi D. A., Fields S., Smith L., Von Hoff D. D. Phase I and pharmacokinetic studies of topotecan administered as a 72 or 120 h continuous infusion. Anticancer Drugs. 1994 Aug;5(4):394–402. doi: 10.1097/00001813-199408000-00002. [DOI] [PubMed] [Google Scholar]
  6. Burris H. A., 3rd, Hanauske A. R., Johnson R. K., Marshall M. H., Kuhn J. G., Hilsenbeck S. G., Von Hoff D. D. Activity of topotecan, a new topoisomerase I inhibitor, against human tumor colony-forming units in vitro. J Natl Cancer Inst. 1992 Dec 2;84(23):1816–1820. doi: 10.1093/jnci/84.23.1816. [DOI] [PubMed] [Google Scholar]
  7. Catimel G., Chabot G. G., Guastalla J. P., Dumortier A., Cote C., Engel C., Gouyette A., Mathieu-Boué A., Mahjoubi M., Clavel M. Phase I and pharmacokinetic study of irinotecan (CPT-11) administered daily for three consecutive days every three weeks in patients with advanced solid tumors. Ann Oncol. 1995 Feb;6(2):133–140. doi: 10.1093/oxfordjournals.annonc.a059108. [DOI] [PubMed] [Google Scholar]
  8. Champoux J. J. Evidence for an intermediate with a single-strand break in the reaction catalyzed by the DNA untwisting enzyme. Proc Natl Acad Sci U S A. 1976 Oct;73(10):3488–3491. doi: 10.1073/pnas.73.10.3488. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Chen A. Y., Yu C., Potmesil M., Wall M. E., Wani M. C., Liu L. F. Camptothecin overcomes MDR1-mediated resistance in human KB carcinoma cells. Cancer Res. 1991 Nov 15;51(22):6039–6044. [PubMed] [Google Scholar]
  10. Chou S., Kaneko M., Nakaya K., Nakamura Y. Induction of differentiation of human and mouse myeloid leukemia cells by camptothecin. Biochem Biophys Res Commun. 1990 Jan 15;166(1):160–167. doi: 10.1016/0006-291x(90)91925-i. [DOI] [PubMed] [Google Scholar]
  11. Covey J. M., Jaxel C., Kohn K. W., Pommier Y. Protein-linked DNA strand breaks induced in mammalian cells by camptothecin, an inhibitor of topoisomerase I. Cancer Res. 1989 Sep 15;49(18):5016–5022. [PubMed] [Google Scholar]
  12. Creaven P. J., Allen L. M., Muggia F. M. Plasma camptothecin (NSC-100880) levels during a 5-day course of treatment: relation to dose and toxicity. Cancer Chemother Rep. 1972 Oct;56(5):573–578. [PubMed] [Google Scholar]
  13. Creemers G. J., Bolis G., Gore M., Scarfone G., Lacave A. J., Guastalla J. P., Despax R., Favalli G., Kreinberg R., Van Belle S. Topotecan, an active drug in the second-line treatment of epithelial ovarian cancer: results of a large European phase II study. J Clin Oncol. 1996 Dec;14(12):3056–3061. doi: 10.1200/JCO.1996.14.12.3056. [DOI] [PubMed] [Google Scholar]
  14. D'Arpa P., Beardmore C., Liu L. F. Involvement of nucleic acid synthesis in cell killing mechanisms of topoisomerase poisons. Cancer Res. 1990 Nov 1;50(21):6919–6924. [PubMed] [Google Scholar]
  15. D'Arpa P., Liu L. F. Topoisomerase-targeting antitumor drugs. Biochim Biophys Acta. 1989 Dec 17;989(2):163–177. doi: 10.1016/0304-419x(89)90041-3. [DOI] [PubMed] [Google Scholar]
  16. Dahut W., Harold N., Takimoto C., Allegra C., Chen A., Hamilton J. M., Arbuck S., Sorensen M., Grollman F., Nakashima H. Phase I and pharmacologic study of 9-aminocamptothecin given by 72-hour infusion in adult cancer patients. J Clin Oncol. 1996 Apr;14(4):1236–1244. doi: 10.1200/JCO.1996.14.4.1236. [DOI] [PubMed] [Google Scholar]
  17. Daoud S. S., Fetouh M. I., Giovanella B. C. Antitumor effect of liposome-incorporated camptothecin in human malignant xenografts. Anticancer Drugs. 1995 Feb;6(1):83–93. doi: 10.1097/00001813-199502000-00010. [DOI] [PubMed] [Google Scholar]
  18. Del Bino G., Darzynkiewicz Z. Camptothecin, teniposide, or 4'-(9-acridinylamino)-3-methanesulfon-m-anisidide, but not mitoxantrone or doxorubicin, induces degradation of nuclear DNA in the S phase of HL-60 cells. Cancer Res. 1991 Feb 15;51(4):1165–1169. [PubMed] [Google Scholar]
  19. Drewinko B., Freireich E. J., Gottlieb J. A. Lethal activity of camptothecin sodium on human lymphoma cells. Cancer Res. 1974 Apr;34(4):747–750. [PubMed] [Google Scholar]
  20. Emerson D. L., Besterman J. M., Brown H. R., Evans M. G., Leitner P. P., Luzzio M. J., Shaffer J. E., Sternbach D. D., Uehling D., Vuong A. In vivo antitumor activity of two new seven-substituted water-soluble camptothecin analogues. Cancer Res. 1995 Feb 1;55(3):603–609. [PubMed] [Google Scholar]
  21. Eng W. K., Faucette L., Johnson R. K., Sternglanz R. Evidence that DNA topoisomerase I is necessary for the cytotoxic effects of camptothecin. Mol Pharmacol. 1988 Dec;34(6):755–760. [PubMed] [Google Scholar]
  22. Furman W. L., Baker S. D., Pratt C. B., Rivera G. K., Evans W. E., Stewart C. F. Escalating systemic exposure of continuous infusion topotecan in children with recurrent acute leukemia. J Clin Oncol. 1996 May;14(5):1504–1511. doi: 10.1200/JCO.1996.14.5.1504. [DOI] [PubMed] [Google Scholar]
  23. Gerrits C. J., Creemers G. J., Schellens J. H., Wissel P., Planting A. S., Kunka R., Selinger K., de Boer-Dennert M., Marijnen Y., Harteveld M. Phase I and pharmacological study of the new topoisomerase I inhibitor GI147211, using a daily x 5 intravenous administration. Br J Cancer. 1996 Mar;73(6):744–750. doi: 10.1038/bjc.1996.130. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Giovanella B. C., Hinz H. R., Kozielski A. J., Stehlin J. S., Jr, Silber R., Potmesil M. Complete growth inhibition of human cancer xenografts in nude mice by treatment with 20-(S)-camptothecin. Cancer Res. 1991 Jun 1;51(11):3052–3055. [PubMed] [Google Scholar]
  25. Giovanella B. C., Stehlin J. S., Wall M. E., Wani M. C., Nicholas A. W., Liu L. F., Silber R., Potmesil M. DNA topoisomerase I--targeted chemotherapy of human colon cancer in xenografts. Science. 1989 Nov 24;246(4933):1046–1048. doi: 10.1126/science.2555920. [DOI] [PubMed] [Google Scholar]
  26. Gottlieb J. A., Guarino A. M., Call J. B., Oliverio V. T., Block J. B. Preliminary pharmacologic and clinical evaluation of camptothecin sodium (NSC-100880). Cancer Chemother Rep. 1970 Dec;54(6):461–470. [PubMed] [Google Scholar]
  27. Gottlieb J. A., Luce J. K. Treatment of malignant melanoma with camptothecin (NSC-100880). Cancer Chemother Rep. 1972 Feb;56(1):103–105. [PubMed] [Google Scholar]
  28. Guarino A. M., Anderson J. B., Starkweather D. K., Chignell C. F. Pharmacologic studies of camptothecin (NSC-100880): distribution, plasma protein binding, and biliary excretion. Cancer Chemother Rep. 1973 Apr;57(2):125–140. [PubMed] [Google Scholar]
  29. Gupta R. S., Gupta R., Eng B., Lock R. B., Ross W. E., Hertzberg R. P., Caranfa M. J., Johnson R. K. Camptothecin-resistant mutants of Chinese hamster ovary cells containing a resistant form of topoisomerase I. Cancer Res. 1988 Nov 15;48(22):6404–6410. [PubMed] [Google Scholar]
  30. Haas N. B., LaCreta F. P., Walczak J., Hudes G. R., Brennan J. M., Ozols R. F., O'Dwyer P. J. Phase I/pharmacokinetic study of topotecan by 24-hour continuous infusion weekly. Cancer Res. 1994 Mar 1;54(5):1220–1226. [PubMed] [Google Scholar]
  31. Hendricks C. B., Rowinsky E. K., Grochow L. B., Donehower R. C., Kaufmann S. H. Effect of P-glycoprotein expression on the accumulation and cytotoxicity of topotecan (SK&F 104864), a new camptothecin analogue. Cancer Res. 1992 Apr 15;52(8):2268–2278. [PubMed] [Google Scholar]
  32. Hinz H. R., Harris N. J., Natelson E. A., Giovanella B. C. Pharmacokinetics of the in vivo and in vitro conversion of 9-nitro-20(S)-camptothecin to 9-amino-20(S)-camptothecin in humans, dogs, and mice. Cancer Res. 1994 Jun 15;54(12):3096–3100. [PubMed] [Google Scholar]
  33. Hochster H., Liebes L., Speyer J., Sorich J., Taubes B., Oratz R., Wernz J., Chachoua A., Raphael B., Vinci R. Z. Phase I trial of low-dose continuous topotecan infusion in patients with cancer: an active and well-tolerated regimen. J Clin Oncol. 1994 Mar;12(3):553–559. doi: 10.1200/JCO.1994.12.3.553. [DOI] [PubMed] [Google Scholar]
  34. Horwitz S. B., Chang C. K., Grollman A. P. Studies on camptothecin. I. Effects of nucleic acid and protein synthesis. Mol Pharmacol. 1971 Nov;7(6):632–644. [PubMed] [Google Scholar]
  35. Horwitz S. B., Horwitz M. S. Effects of camptothecin on the breakage and repair of DNA during the cell cycle. Cancer Res. 1973 Nov;33(11):2834–2836. [PubMed] [Google Scholar]
  36. Horwitz S. B. Novel inhibitors of RNA synthesis. Fed Proc. 1974 Nov;33(11):2281–2287. [PubMed] [Google Scholar]
  37. Houghton P. J., Cheshire P. J., Hallman J. D., 2nd, Lutz L., Friedman H. S., Danks M. K., Houghton J. A. Efficacy of topoisomerase I inhibitors, topotecan and irinotecan, administered at low dose levels in protracted schedules to mice bearing xenografts of human tumors. Cancer Chemother Pharmacol. 1995;36(5):393–403. doi: 10.1007/BF00686188. [DOI] [PubMed] [Google Scholar]
  38. Houghton P. J., Cheshire P. J., Myers L., Stewart C. F., Synold T. W., Houghton J. A. Evaluation of 9-dimethylaminomethyl-10-hydroxycamptothecin against xenografts derived from adult and childhood solid tumors. Cancer Chemother Pharmacol. 1992;31(3):229–239. doi: 10.1007/BF00685553. [DOI] [PubMed] [Google Scholar]
  39. Hsiang Y. H., Lihou M. G., Liu L. F. Arrest of replication forks by drug-stabilized topoisomerase I-DNA cleavable complexes as a mechanism of cell killing by camptothecin. Cancer Res. 1989 Sep 15;49(18):5077–5082. [PubMed] [Google Scholar]
  40. Hsiang Y. H., Liu L. F. Identification of mammalian DNA topoisomerase I as an intracellular target of the anticancer drug camptothecin. Cancer Res. 1988 Apr 1;48(7):1722–1726. [PubMed] [Google Scholar]
  41. Hwang J. L., Shyy S. H., Chen A. Y., Juan C. C., Whang-Peng J. Studies of topoisomerase-specific antitumor drugs in human lymphocytes using rabbit antisera against recombinant human topoisomerase II polypeptide. Cancer Res. 1989 Feb 15;49(4):958–962. [PubMed] [Google Scholar]
  42. Hwong C. L., Chen C. Y., Shang H. F., Hwang J. Increased synthesis and degradation of DNA topoisomerase I during the initial phase of human T lymphocyte proliferation. J Biol Chem. 1993 Sep 5;268(25):18982–18986. [PubMed] [Google Scholar]
  43. Hwong C. L., Chen M. S., Hwang J. L. Phorbol ester transiently increases topoisomerase I mRNA levels in human skin fibroblasts. J Biol Chem. 1989 Sep 5;264(25):14923–14926. [PubMed] [Google Scholar]
  44. Jaxel C., Kohn K. W., Wani M. C., Wall M. E., Pommier Y. Structure-activity study of the actions of camptothecin derivatives on mammalian topoisomerase I: evidence for a specific receptor site and a relation to antitumor activity. Cancer Res. 1989 Mar 15;49(6):1465–1469. [PubMed] [Google Scholar]
  45. Juan C. C., Hwang J. L., Liu A. A., Whang-Peng J., Knutsen T., Huebner K., Croce C. M., Zhang H., Wang J. C., Liu L. F. Human DNA topoisomerase I is encoded by a single-copy gene that maps to chromosome region 20q12-13.2. Proc Natl Acad Sci U S A. 1988 Dec;85(23):8910–8913. doi: 10.1073/pnas.85.23.8910. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. Kantarjian H. M., Beran M., Ellis A., Zwelling L., O'Brien S., Cazenave L., Koller C., Rios M. B., Plunkett W., Keating M. J. Phase I study of Topotecan, a new topoisomerase I inhibitor, in patients with refractory or relapsed acute leukemia. Blood. 1993 Mar 1;81(5):1146–1151. [PubMed] [Google Scholar]
  47. Kanzawa F., Sugimoto Y., Minato K., Kasahara K., Bungo M., Nakagawa K., Fujiwara Y., Liu L. F., Saijo N. Establishment of a camptothecin analogue (CPT-11)-resistant cell line of human non-small cell lung cancer: characterization and mechanism of resistance. Cancer Res. 1990 Sep 15;50(18):5919–5924. [PubMed] [Google Scholar]
  48. Kaufmann S. H. Induction of endonucleolytic DNA cleavage in human acute myelogenous leukemia cells by etoposide, camptothecin, and other cytotoxic anticancer drugs: a cautionary note. Cancer Res. 1989 Nov 1;49(21):5870–5878. [PubMed] [Google Scholar]
  49. Kawato Y., Aonuma M., Hirota Y., Kuga H., Sato K. Intracellular roles of SN-38, a metabolite of the camptothecin derivative CPT-11, in the antitumor effect of CPT-11. Cancer Res. 1991 Aug 15;51(16):4187–4191. [PubMed] [Google Scholar]
  50. Kessel D. Effects of camptothecin on RNA synthesis in leukemia L1210 cells. Biochim Biophys Acta. 1971 Aug 26;246(2):225–232. doi: 10.1016/0005-2787(71)90131-6. [DOI] [PubMed] [Google Scholar]
  51. Kharbanda S., Rubin E., Gunji H., Hinz H., Giovanella B., Pantazis P., Kufe D. Camptothecin and its derivatives induce expression of the c-jun protooncogene in human myeloid leukemia cells. Cancer Res. 1991 Dec 15;51(24):6636–6642. [PubMed] [Google Scholar]
  52. Kjeldsen E., Bonven B. J., Andoh T., Ishii K., Okada K., Bolund L., Westergaard O. Characterization of a camptothecin-resistant human DNA topoisomerase I. J Biol Chem. 1988 Mar 15;263(8):3912–3916. [PubMed] [Google Scholar]
  53. Ling Y. H., Tseng M. T., Nelson J. A. Differentiation induction of human promyelocytic leukemia cells by 10-hydroxycamptothecin, a DNA topoisomerase I inhibitor. Differentiation. 1991 Mar;46(2):135–141. doi: 10.1111/j.1432-0436.1991.tb00873.x. [DOI] [PubMed] [Google Scholar]
  54. Liu L. F., D'Arpa P. Topoisomerase-targeting antitumor drugs: mechanisms of cytotoxicity and resistance. Important Adv Oncol. 1992:79–89. [PubMed] [Google Scholar]
  55. Liu L. F., Miller K. G. Eukaryotic DNA topoisomerases: two forms of type I DNA topoisomerases from HeLa cell nuclei. Proc Natl Acad Sci U S A. 1981 Jun;78(6):3487–3491. doi: 10.1073/pnas.78.6.3487. [DOI] [PMC free article] [PubMed] [Google Scholar]
  56. Lynch T. J., Jr, Kalish L., Strauss G., Elias A., Skarin A., Shulman L. N., Posner M., Frei E., 3rd Phase II study of topotecan in metastatic non-small-cell lung cancer. J Clin Oncol. 1994 Feb;12(2):347–352. doi: 10.1200/JCO.1994.12.2.347. [DOI] [PubMed] [Google Scholar]
  57. McSheehy P. M., Gervasoni M., Lampasona V., Erba E., D'Incalci M. Studies of the differentiation properties of camptothecin in the human leukaemic cells K562. Eur J Cancer. 1991;27(11):1406–1411. doi: 10.1016/0277-5379(91)90021-5. [DOI] [PubMed] [Google Scholar]
  58. Mertens W. C., Eisenhauer E. A., Jolivet J., Ernst S., Moore M., Muldal A. Docetaxel in advanced renal carcinoma. A phase II trial of the National Cancer Institute of Canada Clinical Trials Group. Ann Oncol. 1994 Feb;5(2):185–187. doi: 10.1093/oxfordjournals.annonc.a058776. [DOI] [PubMed] [Google Scholar]
  59. Moertel C. G., Schutt A. J., Reitemeier R. J., Hahn R. G. Phase II study of camptothecin (NSC-100880) in the treatment of advanced gastrointestinal cancer. Cancer Chemother Rep. 1972 Feb;56(1):95–101. [PubMed] [Google Scholar]
  60. Muggia F. M., Creaven P. J., Hansen H. H., Cohen M. H., Selawry O. S. Phase I clinical trial of weekly and daily treatment with camptothecin (NSC-100880): correlation with preclinical studies. Cancer Chemother Rep. 1972 Aug;56(4):515–521. [PubMed] [Google Scholar]
  61. Nakai H., Fukuoka M., Furuse K., Nakao I., Yoshimori K., Ogura T., Hara N., Sakata Y., Saito H., Hasegawa K. [An early phase II study of CPT-11 in primary lung cancer]. Gan To Kagaku Ryoho. 1991 Apr;18(4):607–612. [PubMed] [Google Scholar]
  62. Negoro S., Fukuoka M., Niitani H., Suzuki A., Nakabayashi T., Kimura M., Motomiya M., Kurita Y., Hasegawa K., Kuriyama T. [A phase II study of CPT-11, a camptothecin derivative, in patients with primary lung cancer. CPT-11 Cooperative Study Group]. Gan To Kagaku Ryoho. 1991 May;18(6):1013–1019. [PubMed] [Google Scholar]
  63. Nitiss J., Wang J. C. DNA topoisomerase-targeting antitumor drugs can be studied in yeast. Proc Natl Acad Sci U S A. 1988 Oct;85(20):7501–7505. doi: 10.1073/pnas.85.20.7501. [DOI] [PMC free article] [PubMed] [Google Scholar]
  64. Ohe Y., Sasaki Y., Shinkai T., Eguchi K., Tamura T., Kojima A., Kunikane H., Okamoto H., Karato A., Ohmatsu H. Phase I study and pharmacokinetics of CPT-11 with 5-day continuous infusion. J Natl Cancer Inst. 1992 Jun 17;84(12):972–974. doi: 10.1093/jnci/84.12.972. [DOI] [PubMed] [Google Scholar]
  65. Ohno R., Okada K., Masaoka T., Kuramoto A., Arima T., Yoshida Y., Ariyoshi H., Ichimaru M., Sakai Y., Oguro M. An early phase II study of CPT-11: a new derivative of camptothecin, for the treatment of leukemia and lymphoma. J Clin Oncol. 1990 Nov;8(11):1907–1912. doi: 10.1200/JCO.1990.8.11.1907. [DOI] [PubMed] [Google Scholar]
  66. Pantazis P., Early J. A., Kozielski A. J., Mendoza J. T., Hinz H. R., Giovanella B. C. Regression of human breast carcinoma tumors in immunodeficient mice treated with 9-nitrocamptothecin: differential response of nontumorigenic and tumorigenic human breast cells in vitro. Cancer Res. 1993 Apr 1;53(7):1577–1582. [PubMed] [Google Scholar]
  67. Pantazis P., Harris N., Mendoza J., Giovanella B. Conversion of 9-nitro-camptothecin to 9-amino-camptothecin by human blood cells in vitro. Eur J Haematol. 1994 Oct;53(4):246–248. doi: 10.1111/j.1600-0609.1994.tb00199.x. [DOI] [PubMed] [Google Scholar]
  68. Pantazis P., Hinz H. R., Mendoza J. T., Kozielski A. J., Williams L. J., Jr, Stehlin J. S., Jr, Giovanella B. C. Complete inhibition of growth followed by death of human malignant melanoma cells in vitro and regression of human melanoma xenografts in immunodeficient mice induced by camptothecins. Cancer Res. 1992 Jul 15;52(14):3980–3987. [PubMed] [Google Scholar]
  69. Pantazis P., Kozielski A. J., Mendoza J. T., Early J. A., Hinz H. R., Giovanella B. C. Camptothecin derivatives induce regression of human ovarian carcinomas grown in nude mice and distinguish between non-tumorigenic and tumorigenic cells in vitro. Int J Cancer. 1993 Mar 12;53(5):863–871. doi: 10.1002/ijc.2910530526. [DOI] [PubMed] [Google Scholar]
  70. Pantazis P., Kozielski A. J., Vardeman D. M., Petry E. R., Giovanella B. C. Efficacy of camptothecin congeners in the treatment of human breast carcinoma xenografts. Oncol Res. 1993;5(8):273–281. [PubMed] [Google Scholar]
  71. Pantazis P., Kozielski A., Rodriguez R., Petry E., Wani M., Wall M., Giovanella B. Therapeutic efficacy of camptothecin derivatives against human malignant melanoma xenografts. Melanoma Res. 1994 Feb;4(1):5–10. doi: 10.1097/00008390-199402000-00002. [DOI] [PubMed] [Google Scholar]
  72. Perez-Soler R., Fossella F. V., Glisson B. S., Lee J. S., Murphy W. K., Shin D. M., Kemp B. L., Lee J. J., Kane J., Robinson R. A. Phase II study of topotecan in patients with advanced non-small-cell lung cancer previously untreated with chemotherapy. J Clin Oncol. 1996 Feb;14(2):503–513. doi: 10.1200/JCO.1996.14.2.503. [DOI] [PubMed] [Google Scholar]
  73. Pratt C. B., Stewart C., Santana V. M., Bowman L., Furman W., Ochs J., Marina N., Kuttesch J. F., Heideman R., Sandlund J. T. Phase I study of topotecan for pediatric patients with malignant solid tumors. J Clin Oncol. 1994 Mar;12(3):539–543. doi: 10.1200/JCO.1994.12.3.539. [DOI] [PubMed] [Google Scholar]
  74. Puc H. S., Bajorin D. F., Bosl G. J., Amsterdam A., Motzer R. J. Phase II trial of topotecan in patients with cisplatin-refractory germ cell tumors. Invest New Drugs. 1995;13(2):163–165. doi: 10.1007/BF00872866. [DOI] [PubMed] [Google Scholar]
  75. Rowinsky E. K., Grochow L. B., Hendricks C. B., Ettinger D. S., Forastiere A. A., Hurowitz L. A., McGuire W. P., Sartorius S. E., Lubejko B. G., Kaufmann S. H. Phase I and pharmacologic study of topotecan: a novel topoisomerase I inhibitor. J Clin Oncol. 1992 Apr;10(4):647–656. doi: 10.1200/JCO.1992.10.4.647. [DOI] [PubMed] [Google Scholar]
  76. Samuels D. S., Shimizu N. DNA topoisomerase I phosphorylation in murine fibroblasts treated with 12-O-tetradecanoylphorbol-13-acetate and in vitro by protein kinase. J Biol Chem. 1992 Jun 5;267(16):11156–11162. [PubMed] [Google Scholar]
  77. Schaeppi U., Fleischman R. W., Cooney D. A. Toxicity of camptothecin (NSC-100880). Cancer Chemother Rep 3. 1974 Sep;5(1):25–36. [PubMed] [Google Scholar]
  78. Schellens J. H., Creemers G. J., Beijnen J. H., Rosing H., de Boer-Dennert M., McDonald M., Davies B., Verweij J. Bioavailability and pharmacokinetics of oral topotecan: a new topoisomerase I inhibitor. Br J Cancer. 1996 May;73(10):1268–1271. doi: 10.1038/bjc.1996.243. [DOI] [PMC free article] [PubMed] [Google Scholar]
  79. Stewart A. F., Schütz G. Camptothecin-induced in vivo topoisomerase I cleavages in the transcriptionally active tyrosine aminotransferase gene. Cell. 1987 Sep 25;50(7):1109–1117. doi: 10.1016/0092-8674(87)90177-2. [DOI] [PubMed] [Google Scholar]
  80. Subramanian D., Kraut E., Staubus A., Young D. C., Muller M. T. Analysis of topoisomerase I/DNA complexes in patients administered topotecan. Cancer Res. 1995 May 15;55(10):2097–2103. [PubMed] [Google Scholar]
  81. Sugimoto Y., Tsukahara S., Oh-hara T., Isoe T., Tsuruo T. Decreased expression of DNA topoisomerase I in camptothecin-resistant tumor cell lines as determined by a monoclonal antibody. Cancer Res. 1990 Nov 1;50(21):6925–6930. [PubMed] [Google Scholar]
  82. Takeda S., Shimazoe T., Sato K., Sugimoto Y., Tsuruo T., Kono A. Differential expression of DNA topoisomerase I gene between CPT-11 acquired- and native-resistant human pancreatic tumor cell lines: detected by RNA/PCR-based quantitation assay. Biochem Biophys Res Commun. 1992 Apr 30;184(2):618–625. doi: 10.1016/0006-291x(92)90634-w. [DOI] [PubMed] [Google Scholar]
  83. Takeuchi S., Takamizawa H., Takeda Y., Ohkawa T., Tamaya T., Noda K., Sugawa T., Sekiba K., Yakushiji M., Taguchi T. [An early phase II study of CPT-11 in gynecologic cancers. Research Group of CPT-11 in Gynecologic Cancers]. Gan To Kagaku Ryoho. 1991 Apr;18(4):579–584. [PubMed] [Google Scholar]
  84. Tanizawa A., Pommier Y. Topoisomerase I alteration in a camptothecin-resistant cell line derived from Chinese hamster DC3F cells in culture. Cancer Res. 1992 Apr 1;52(7):1848–1854. [PubMed] [Google Scholar]
  85. Verweij J., Lund B., Beijnen J., Planting A., de Boer-Dennert M., Koier I., Rosing H., Hansen H. Phase I and pharmacokinetics study of topotecan, a new topoisomerase I inhibitor. Ann Oncol. 1993 Sep;4(8):673–678. doi: 10.1093/oxfordjournals.annonc.a058623. [DOI] [PubMed] [Google Scholar]
  86. Zhang H., Wang J. C., Liu L. F. Involvement of DNA topoisomerase I in transcription of human ribosomal RNA genes. Proc Natl Acad Sci U S A. 1988 Feb;85(4):1060–1064. doi: 10.1073/pnas.85.4.1060. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from British Journal of Cancer are provided here courtesy of Cancer Research UK

RESOURCES